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Resistance training-induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage
The Journal of Physiology
Abstract
Key points:
Skeletal muscle hypertrophy is one of the main outcomes from resistance training (RT), but how it is modulated throughout training is still unknown. We show that changes in myofibrillar protein synthesis (MyoPS) after an initial resistance exercise (RE) bout in the first week of RT (T1) were greater than those seen post-RE at the third (T2) and tenth week (T3) of RT, with values being similar at T2 and T3. Muscle damage (Z-band streaming) was the highest during post-RE recovery at T1, lower at T2 and minimal at T3. When muscle damage was the highest, so was the integrated MyoPS (at T1), but neither were related to hypertrophy; however, integrated MyoPS at T2 and T3 were correlated with hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent increases in MyoPS mainly after a progressive attenuation of muscle damage.
Abstract:
Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are still unknown. To investigate how muscle hypertrophy is modulated through RT, we measured day-to-day integrated myofibrillar protein synthesis (MyoPS) using deuterium oxide and assessed muscle damage at the beginning (T1), at 3 weeks (T2) and at 10 weeks of RT (T3). Ten young men (27 (1) years, mean (SEM)) had muscle biopsies (vastus lateralis) taken to measure integrated MyoPS and muscle damage (Z-band streaming and indirect parameters) before, and 24 h and 48 h post resistance exercise (post-RE) at T1, T2 and T3. Fibre cross-sectional area (fCSA) was evaluated using biopsies at T1, T2 and T3. Increases in fCSA were observed only at T3 (P = 0.017). Changes in MyoPS post-RE at T1, T2 and T3 were greater at T1 (P < 0.03) than at T2 and T3 (similar values between T2 and T3). Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. The change in MyoPS post-RE at both T2 and T3, but not at T1, was strongly correlated (r ≈ 0.9, P < 0.04) with muscle hypertrophy. Initial MyoPS response post-RE in an RT programme is not directed to support muscle hypertrophy, coinciding with the greatest muscle damage. However, integrated MyoPS is quickly 'refined' by 3 weeks of RT, and is related to muscle hypertrophy. We conclude that muscle hypertrophy is the result of accumulated intermittent changes in MyoPS post-RE in RT, which coincides with progressive attenuation of muscle damage.
... Muscle hypertrophy is the result of accumulated short-term increases in myofibrillar protein synthesis (MyoPS) after muscle damage has decreased [43]. In a human study, muscle protein synthesis rate (MPS) increases 50% over baseline for 4 hours after heavy resistance training, and then, at 24 hours after the training session has finished, MPS is 109% greater than at baseline, but MPS drops off so rapidly that by 36 hours it's back to the 14% baseline rate [44]. ...
... Muscle damage peaked after the initial workout in week one but decreased gradually in weeks three and ten. Similarly, myofibrillar protein synthesis was highest in week one but lessened in weeks three and ten [43]. When an individual hits the gym for some resistance training, the muscles grow bigger -that's muscle hypertrophy. ...
... Results Notes [43] To determine whether muscle hypertrophy is the outcome of RT 10 men, 1,3,10 week program ...
This systematic review examines the synergistic and individual influences of resistance exercise, dietary protein supplementation, and sleep/recovery on muscle protein synthesis (MPS). Electronic databases such as Scopus, Google Scholar, and Web of Science were extensively used. Studies were selected based on relevance to the criteria and were ensured to be directly applicable to the objectives. Research indicates that a protein dose of 20 to 25 grams maximally stimulates MPS post-resistance training. It is observed that physically frail individuals aged 76 to 92 and middle-aged adults aged 62 to 74 have lower mixed muscle protein synthetic rates than individuals aged 20 to 32. High-whey protein and leucine-enriched supplements enhance MPS more efficiently than standard dairy products in older adults engaged in resistance programs. Similarly, protein intake before sleep boosts overnight MPS rates, which helps prevent muscle loss associated with sleep debt, exercise-induced damage, and muscle-wasting conditions like sarcopenia and cachexia. Resistance exercise is a functional intervention to achieve muscular adaptation and improve function. Future research should focus on variables such as fluctuating fitness levels, age groups, genetics, and lifestyle factors to generate more accurate and beneficial results.
... Under strenuous stimuli (eccentric contraction), contractile myofilaments no longer overlap and 'pop,' causing physical disruption to the sarcomere [197]. Remodeling to adapt to such damage is focused on structural maintenance of sarcomere stability, which could occur rapidly without a drastic increase in muscle fiber cross-sectional area [198]. This observation may explain why some markers of 'damage' are attenuated rapidly following only a few bouts of unaccustomed exercise without measurable hypertrophy or other (known) significant adaptations [198]. ...
... Remodeling to adapt to such damage is focused on structural maintenance of sarcomere stability, which could occur rapidly without a drastic increase in muscle fiber cross-sectional area [198]. This observation may explain why some markers of 'damage' are attenuated rapidly following only a few bouts of unaccustomed exercise without measurable hypertrophy or other (known) significant adaptations [198]. Exercise-induced muscle damage is attenuated following as little as a single session of exercise and tends to decrease even more with subsequent bouts; however, significant hypertrophic adaptation is typically not reliably measurable until 6 weeks (12-15 bouts) of RT or later [199]. ...
... We propose that the initial (early training) stimulation of protein synthesis is, at least in untrained persons, more directly related to the repair and/or remodeling of skeletal muscle. At the same time, myofibrillar hypertrophy may occur with progressive attenuation of damage after subsequent bouts with chronic RT [198]. Taken altogether, although damage is commonly associated with an elevation in protein synthesis and breakdown, it does not appear to be an essential factor for anabolic signaling or hypertrophy to occur in skeletal muscle. ...
... MPS is quantitatively assessed as an average over short (i.e., hourly) or long (i.e., days, weeks, and months) time durations [4][5][6][7][8][9][10][11], via the precursor-product method. Tis method involves the administration of naturally occurring stable isotopically labelled amino acids combined with sampling of biological fuids (e.g., plasma and/or saliva) and skeletal muscle tissue (via percutaneous biopsy), and mass spectrometry (MS), which are used to determine the rate at which the labelled amino acids are incorporated into skeletal muscle protein over a predefned period of time [2,3]. ...
... Tis approach of quantifying MPS requires infusion of isotopically labelled amino acids and/or amino acid precursors (e.g., [1- 13 6 ] phenylalanine), intra-venous/arterial cannulation, and multiple biopsies [2,3,12]. Consequently, experimental trials are de facto short (i.e., hours) and conducted under tightly controlled laboratory conditions, when determined over longer periods (i.e., days); usually, the oral dosing of deuterium oxide (D2O) is applied [9][10][11]13]. ...
... Te eligibility criteria for this review were as follows: (1) published in peer-reviewed, English language journals; (2) healthy adult humans, nonobese; (3) RE performed, operationally defned as a single bout of exercise against external resistance applied to a targeted muscle group; (4) a validated and direct method of measuring mixed muscle and/or myofbrillar protein synthesis (e.g., precursor-product methods using labelled amino acids or D 2 O), and indirect estimates of MPS, such as measures of whole-body protein synthesis, net balance, and/or protein turnover, were not included; (5) fasted/postabsorptive state assessment of MPS (e.g., dietary intervention, ingestion of supplement, or standard meals during assessment period, Refs. [5,[9][10][11][33][34][35] were excluded), ingestion of nonnutritive/noncaloric placebos were permitted, (e.g., water, noncaloric artifcially favoured water, and cellulose); (6) within-subject fasted/resting (i.e., basal) MPS comparator, obtained under the same experimental/physiological state/ conditions in close temporal proximity, (e.g., pretest bilateral/unilateral or contralateral non-RE limb, Refs. [36][37][38][39][40] were excluded); (7) studies that utilised primary and/or adjuvant interventions in conjunction with RE were excluded (e.g., aerobic exercise, high-intensity interval training, blood fow restriction training, hypoxic training, pharmaceuticals, and ergogenic aids); and (8) data not published elsewhere (pseudo-replication), e.g., [41]. ...
Methods
Five electronic databases (PubMed (Medline), Web of Science, Embase, Sport Discus, and Cochrane Library) were searched for controlled trials that assessed the MPS response to RE in healthy, adult humans, postabsorptive state. Individual study and random-effects meta-analysis arewere used to inform the effects of RE and covariates on MPS. Results from 79 controlled trials with 237 participants were analysed.
Results
Analysis of the pooled effects revealed robust increases in MPS following RE (weighted mean difference (WMD): 0.032% h⁻¹, 95% CI: [0.024, 0.041] % h⁻¹, I² = 92%, k = 37, P < 0.001). However, the magnitude of the increase in MPS was lower in older adults (>50 y: WMD: 0.015% h⁻¹, 95% CI: [0.007, 0.022] % h⁻¹, I² = 76%, k = 12, P = 0.002) compared to younger adults (<35 y: WMD: 0.041% h⁻¹, 95% CI: [0.030, 0.052] % h⁻¹, I² = 88%, k = 25, P < 0.001). Individual studies have reported that the temporal proximity of the RE, muscle group, muscle protein fraction, RE training experience, and the loading parameters of the RE (i.e., intensity, workload, and effort) appeared to affect the MPS response to RE, whereas sex or type of muscle contraction does not.
Conclusion
A single bout of RE can sustain measurable increases in postabsorptive MPS soon after RE cessation and up to 48 h post-RE. However, there is substantial heterogeneity in the magnitude and time course of the MPS response between trials, which appears to be influenced by participants' age and/or the loading parameters of the RE itself.
... Previous studies have shown a robust increase in MPS within the first 24 h after a single bout of resistance exercise [22,23]. Repeated resistance exercise (i.e., RT) leads to chronic muscle hypertrophy by creating a positive net protein balance [24]. However, when assessed within 24-48 h after a single resistance exercise session, it can also result in delayed onset muscle soreness (DOMS), increased muscle damage (i.e., Z-band streaming area), and increased levels of indirect markers of muscle damage such as creatine kinase and lactate dehydrogenase [24,25]. ...
... Repeated resistance exercise (i.e., RT) leads to chronic muscle hypertrophy by creating a positive net protein balance [24]. However, when assessed within 24-48 h after a single resistance exercise session, it can also result in delayed onset muscle soreness (DOMS), increased muscle damage (i.e., Z-band streaming area), and increased levels of indirect markers of muscle damage such as creatine kinase and lactate dehydrogenase [24,25]. Although the magnitude of muscle damage and DOMS gradually decreases with repeated RT sessions, even in untrained participants [26,27], the magnitude of those was five times higher in the untrained state than in the pre-trained state [28]. ...
... Moreover, an initial increase in a post-RT MPS primarily serves for repair and remodeling from muscle damage caused by unaccustomed bouts of RT rather than contributing directly to muscle growth. Notably, substantial muscle hypertrophy is strongly correlated with the summation of post-RT MPS and progressive mitigation of muscle damage during the late phase of a 10-week RT program [24,32]. A recent meta-analysis of RCTs showed that 8-36 weeks of RT led to a significant increase in muscular strength (e.g., handgrip strength and lower extremity muscle strength) and physical performance but did not improve muscle mass in healthy older adults with sarcopenia [33]. ...
Background
Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT).
Methods
We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose–response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels.
Results
Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3–4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12–23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3–4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3–4 days/week, regardless of whether the RT duration was 1–2 years or more than 2 years.
Conclusions
Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3–4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years.
... A key event in the stimulation of MyoPS-which underpins hypertrophy-involves mechanotransducive signaling through the mechanistic target of rapamycin complex 1 (mTORC1). 16 Conversely, 5′-adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor that mediates reductions in energyconsuming processes, such as mTORC1 signaling and MyoPS. 17 Early work in rodents demonstrated selective activation of these pathways with aerobic-or resistancelike stimuli, [18][19][20] contributing to the theory of "molecular incompatibility" between concurrent exercise modes. ...
... 68 However, previous studies have shown acute rates of myofibrillar and mixed muscle protein synthesis (i.e., ~5 h post-exercise) are similar between concurrent and singlemode exercise. [12][13][14][15] Increases in protein synthesis can persist for 24-48 h post-exercise 16,69 ; however, these studies used intravenous tracer infusions (which are limited to short measurement periods 70 ) and studied participants of different training statuses (e.g., sedentary middle-aged, 14 moderately trained, 12,13 and collegiate athletes 15 ). To our knowledge, our study is the first to use D 2 O to characterize the MyoPS response to a week of concurrent and resistance-only training, under free-living conditions, during two distinct periods within the same cohort (i.e., Week 1, 'training-naïve' vs. Week 10, 'training-accustomed'). ...
... The pre-training MyoPS rates in all groups (~1.4%/day; Figure 3) resemble other studies in similar populations. 16,52,71 At the end of Week 1, MyoPS rates increased comparably between groups (~1.8% to 2.0%/ day; Figure 3) and were similar in magnitude to other studies involving HIIE 72 and resistance exercise. 16,52 Performing HIIE before or after resistance exercise did not clearly attenuate the MyoPS response; the relative fold-changes from rest were similar between groups (~1.3-to 1.4-fold). ...
Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free‐living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance‐only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance‐only exercise (RE, n = 8), RE plus high‐intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre‐ and post‐training, was used to determine MyoPS using orally administered deuterium oxide (D2O). In both weeks, MyoPS rates were comparable between groups. Post‐exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order‐dependent responses. In Week 10, exercise‐induced changes in MyoPS and some genes (PGC‐1ɑ and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance‐only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.
... Functional parameters are used by several authors as an indirect method to evaluate EIMD [29,[52][53][54][55]. There are many options commonly incorporated into EIMD studies that can be accessible to coaches and fitness instructors [22,26,29,[52][53][54][55]. ...
... Functional parameters are used by several authors as an indirect method to evaluate EIMD [29,[52][53][54][55]. There are many options commonly incorporated into EIMD studies that can be accessible to coaches and fitness instructors [22,26,29,[52][53][54][55]. Since HIIT protocols were able to promote changes in markers of exercise-induced muscle damage, monitoring post-session responses can be accessible and help coaches and fitness instructors improve design strategies for HIIT prescription. ...
... In addition, some considerations should be mentioned. First, curiously, although some studies had used other methods such as ultrasound [29,52], muscular biopsy [22,53,54], and molecular parameters [22,53,54], no studies found in our search analyzed the EIMD using these methods after HIIT. It could be a new methodological strategy to improve knowledge about EIMD and HIIT. ...
High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical and metabolic stress generated during the session can lead to the occurrence of exercise-induced muscle damage. Therefore, this study aimed to describe, by means of a systematic review, the effects of a single HIIT session on exercise-induced muscle damage. A total of 43 studies were found in the Medline/PubMed Science Direct/Embase/Scielo/CINAHL/LILACS databases; however, after applying the exclusion criteria, only 15 articles were considered eligible for this review. The total sample was 315 participants. Among them, 77.2% were men, 13.3% were women and 9.5 uninformed. Their age ranged from 20.1 ± 2 to 47.8 ± 7.5 years. HIIT protocols included running with ergometers (n = 6), CrossFit-specific exercises (n = 2), running without ergometers (n = 3), swimming (n = 1), the Wingate test on stationary bicycles (n = 2), and cycling (n = 1). The most applied intensity controls were %vVO2max, “all out”, MV, MAV, Vmax, and HRreserve%. The most used markers to evaluate muscle damage were creatine kinase, myoglobin, and lactate dehydrogenase. The time for muscle damage assessment ranged from immediately post exercise to seven days. HIIT protocols were able to promote changes in markers of exercise-induced muscle damage, evidenced by increases in CK, Mb, LDH, AST, ALT, pain, and muscle circumference observed mainly immediately and 24 h after the HIIT session.
... As such, it is noteworthy that prior data were collected over a few hours post-exercise, with the link to eventual effects on muscle growth being tenuous (Mitchell et al., 2015). By contrast, recent developments in the use of deuterated water to assess integrated diurnal muscle protein synthesis showed improved associations with muscle hypertrophy (Damas et al., 2016). Our data provide an assessment of muscle protein synthesis over 5 days in free-living conditions with two controlled bouts of resistance exercise. ...
... Our data provide an assessment of muscle protein synthesis over 5 days in free-living conditions with two controlled bouts of resistance exercise. Using this method of assessing MPS incorporates days of exposure to RE and the overall hormonal milieu (Damas et al., 2016) and would have incorporated peak oestrogen and peak progesterone concentrations. Albeit acknowledging that MPS is not a measure of net muscle protein accretion (or muscle hypertrophy), menstrual cycle phase did not affect muscle protein synthesis. ...
It has been hypothesised that skeletal muscle protein turnover is affected by menstrual cycle phase with a more anabolic environment during the follicular vs. the luteal phase. We assessed the influence of menstrual cycle phase on muscle protein synthesis and myofibrillar protein breakdown in response to 6 days of controlled resistance exercise in young females during peak oestrogen and peak progesterone, using stable isotopes, unbiased metabolomics and muscle biopsies. We used comprehensive menstrual cycle phase‐detection methods, including cycle tracking, blood samples and urinary test kits, to classify menstrual phases. Participants (n = 12) completed two 6 day study phases in a randomised order: late follicular phase and mid‐luteal phase. Participants performed unilateral resistance exercise in each menstrual cycle phase, exercising the contralateral leg in each phase in a counterbalanced manner. Follicular phase myofibrillar protein synthesis (MPS) rates were 1.33 ± 0.27% d⁻¹ in the control leg and 1.52 ± 0.27% d⁻¹ in the exercise leg. Luteal phase MPS was 1.28 ± 0.27% d⁻¹ in the control leg and 1.46 ± 0.25% d⁻¹ in the exercise leg. We observed a significant effect of exercise (P < 0.001) but no effect of cycle phase or interaction. There was no significant effect of menstrual cycle phase on whole‐body myofibrillar protein breakdown (P = 0.24). Using unbiased metabolomics, we observed no notable phase‐specific changes in circulating blood metabolites associated with any particular menstrual cycle phase. Fluctuations in endogenous ovarian hormones influenced neither MPS, nor MPB in response to resistance exercise. Skeletal muscle is not more anabolically responsive to resistance exercise in a particular menstrual cycle phase. image
Key points
It has been hypothesised that the follicular (peak oestrogen) vs. the luteal (peak progesterone) phase of the menstrual cycle is more advantageous for skeletal muscle anabolism in response to resistance exercise.
Using best practice methods to assess menstrual cycle status, we measured integrated (over 6 days) muscle protein synthesis (MPS) and myofibrillar protein breakdown (MPB) following resistance exercise in females (n = 12) in their follicular and luteal phases.
We observed the expected differences in oestrogen and progesterone concentrations that confirmed our participants’ menstrual cycle phase; however, there were no notable metabolic pathway differences, as measured using metabolomics, between cycle phases.
We observed that resistance exercise stimulated MPS, but there was no effect of menstrual cycle phase on either resting or exercise‐stimulated MPS or MPB.
Our data show no greater anabolic effect of resistance exercise in the follicular vs. the luteal phase of the menstrual cycle.
... However, for those unaccustomed to such practices, the initial engagement in various training programs often presents a significant barrier [5,6]. Muscle damage scenarios or delayed onset muscle soreness (DOMS) can emerge within hours after or upon completion of the activity, persisting for up to 7 days [7,8]. Aside from the discomfort experienced by new participants, a comprehensive review highlights that the first few weeks of resistance training and the potential muscular adaptations primarily involve tissue repair [8], with outcomes such as hypertrophy being evident only after 18 sessions. ...
... Muscle damage scenarios or delayed onset muscle soreness (DOMS) can emerge within hours after or upon completion of the activity, persisting for up to 7 days [7,8]. Aside from the discomfort experienced by new participants, a comprehensive review highlights that the first few weeks of resistance training and the potential muscular adaptations primarily involve tissue repair [8], with outcomes such as hypertrophy being evident only after 18 sessions. ...
Background/objectives: The oral administration of hydrolyzed collagen peptides is a scientifically validated intervention for enhancing skeletal muscle health and performance. This integrative review consolidates the evidence supporting the use of low molecular weight collagen peptides (2000–3500 daltons) for their superior bioavailability and absorption. Our objective was to review the effects of collagen peptide or hydrolyzed collagen supplementation on muscle damage, recovery, and construction related to physical exercise. Methods: A bibliographic search was conducted in major English-language databases, including PubMed/Medline, using terms like “Peptides Collagen and Damage” and “collagen peptides AND Soreness Muscle”. This review followed PRISMA guidelines, with bias risk assessed via the PEDro scale. The inclusion criteria were (a) randomized clinical trials, (b) randomized studies in humans with a control or placebo group, (c) studies assessing muscle damage or delayed onset muscle soreness via physiological markers or strength performance tests, and (d) studies using hydrolyzed collagen or collagen peptides. Results: Initially, 752 articles were identified. After applying the inclusion and exclusion criteria, including duplicate removal, eight articles with 286 participants were included. Of these, 130 participants received collagen peptide supplementation, while 171 received a placebo or control. Conclusion: This integrative review supports the potential of collagen peptide supplementation to mitigate muscle stress from acute strenuous resistance training. However, due to the methodological heterogeneity among the studies, further clinical trials are needed to clarify the mechanisms underlying muscle improvement with collagen supplementation.
... A physiological explanation for this disconnect relates to the training status of the studied participants. Trommelen et al. (2023) recruited recreationally active, but not resistance-trained, young men, and previous work suggests that no relationship exists between the acute response of myofibrillar MPS to an initial resistance exercise bout and chronic changes in muscle mass following a period of resistance training (Damas et al., 2016). Instead, it has been proposed that the increased response of MPS to a novel resistance exercise stimulus and protein ingestion is likely related more to the repair and remodeling of existing older, damaged muscle proteins, rather than to driving a functional muscle hypertrophic response (Damas et al., 2016;Witard et al., 2022). ...
... Trommelen et al. (2023) recruited recreationally active, but not resistance-trained, young men, and previous work suggests that no relationship exists between the acute response of myofibrillar MPS to an initial resistance exercise bout and chronic changes in muscle mass following a period of resistance training (Damas et al., 2016). Instead, it has been proposed that the increased response of MPS to a novel resistance exercise stimulus and protein ingestion is likely related more to the repair and remodeling of existing older, damaged muscle proteins, rather than to driving a functional muscle hypertrophic response (Damas et al., 2016;Witard et al., 2022). ...
A comprehensive recent study by Trommelen et al. demonstrated that muscle tissue exhibits a greater capacity to incorporate exogenous exogenous protein-derived amino acids into bound muscle protein than was previously appreciated, at least when measured in “anabolically sensitive,” recreationally active (but not resistance-trained), young men following resistance exercise. Moreover, this study demonstrated that the duration of the postprandial period is modulated by the dose of ingested protein contained within a meal, that is, the postexercise muscle protein synthesis response to protein ingestion was more prolonged in 100PRO than 25PRO. Both observations represent important scientific advances in the field of protein metabolism. However, we respectfully caution that the practical implications of these findings may have been misinterpreted, at least in terms of dismissing the concept of protein meal distribution as an important factor in optimizing muscle tissue anabolism and/or metabolic health. Moreover, based on emerging evidence, this idea that the anabolic response to protein ingestion has no upper limit does not appear to translate to resistance-trained young women.
... This orchestrated function of both proteolytic pathways is crucial for muscle remodeling (Hyatt and Powers 2020). Evidence suggests that there is upregulation after a bout of exercise (Godwin et al. 2023b;Féasson et al. 2002;Nedergaard et al. 2007), which may be attenuated after subsequent bouts (Nedergaard et al. 2007;Stupka et al. 2001;Willoughby et al. 2003;Mascher et al. 2008) due to the "repetitive bout effect" phenomenon (attenuation of RT-induced muscle damage) (Damas et al. 2016a). However, novel insights have emerged regarding the importance of the processes of degradation and remodeling in skeletal muscle, suggesting that if the RT stimulus is continued, these activities could remain upregulated, even with an attenuation of muscle damage. ...
... However, novel insights have emerged regarding the importance of the processes of degradation and remodeling in skeletal muscle, suggesting that if the RT stimulus is continued, these activities could remain upregulated, even with an attenuation of muscle damage. While structural disruptions and microlesions are gradually reduced during the initial weeks of RT (Damas et al. 2016a), the need for proteolysis and remodeling is likely sustained due to studies showing that muscle hypertrophy ensues months into training (Ogasawara et al. 2012;DeFreitas et al. 2011). Moreover, it has been suggested that muscle growth increases the need to recycle cellular components that might have become inefficient and the need for an intracellular pool of free amino acids (Höhfeld et al. 2021;Roberts et al. 2023). ...
Purpose
Resistance training (RT) induces muscle growth at varying rates across RT phases, and evidence suggests that the muscle-molecular responses to training bouts become refined or attenuated in the trained state. This study examined how proteolysis-related biomarkers and extracellular matrix (ECM) remodeling factors respond to a bout of RT in the untrained (UT) and trained (T) state.
Methods
Participants (19 women and 19 men) underwent 10 weeks of RT. Biopsies of vastus lateralis were collected before and after (24 h) the first (UT) and last (T) sessions. Vastus lateralis cross-sectional area (CSA) was assessed before and after the experimental period.
Results
There were increases in muscle and type II fiber CSAs. In both the UT and T states, calpain activity was upregulated and calpain-1/-2 protein expression was downregulated from Pre to 24 h. Calpain-2 was higher in the T state. Proteasome activity and 20S proteasome protein expression were upregulated from Pre to 24 h in both the UT and T. However, proteasome activity levels were lower in the T state. The expression of poly-ubiquitinated proteins was unchanged. MMP activity was downregulated, and MMP-9 protein expression was elevated from Pre to 24 h in UT and T. Although MMP-14 protein expression was acutely unchanged, this marker was lower in T state. TIMP-1 protein levels were reduced Pre to 24 h in UT and T, while TIMP-2 protein levels were unchanged.
Conclusion
Our results are the first to show that RT does not attenuate the acute-induced response of proteolysis and ECM remodeling-related biomarkers.
... Moreover, HIIT augments phosphorylation levels of the mechanistic target of rapamycin (mTOR) signals, p70 S6 kinase (p70S6 K), ribosomal protein S6 (S6) 19 in young and old mice. In addition, HIIT can induce substantial muscle damage, which is a profound stimulus to activate muscle satellite cells 20,21 . Mechanical damage associated with HIIT also causes a progressive increase in myonuclei, increasing muscle fiber size 22,23 . ...
We tested the hypothesis that improper myonuclei arrangement and morphology are involved in diabetes-induced myofiber atrophy and whether and how high-intensity interval training (HIIT) affects these impairments in isolated skeletal muscle myofibers. STZ-induced diabetes decreased muscle fiber cross-sectional area (CSA) mediated by reduced myonuclear number, enhanced nuclear apoptotic, and failed nuclear accretion from satellite cells. STZ-induced muscle atrophy was accompanied by improper nuclear positioning (sinus of the maximum diameter angles and distance between adjacent myonuclei) and morphology (maximum diameter, area, and volume of the nuclei), which was mediated by suppressed expression of proteins involved in nuclear positioning including KIF5B, dynein, and Nesprin1. Disturbing nuclear positioning by inhibition of Kinsein1 activity reduced CSA to a greater extent than in diabetes alone, suggesting STZ-induced muscle atrophy is mediated by changes in nuclear positioning. HIIT alleviated the STZ-induced decline in muscle CSA and myonuclei per fiber by restoring myonuclear morphometry impairments and improper nuclear positioning to the normal level. HIIT-induced increase in muscle CSA deterred by inhibition of Kinesin1 activity, suggesting its effect is mediated by proper nuclear positioning. These findings suggest that normal nuclear positioning are required for the changes in fiber size properties associated with HIIT in diabetic skeletal muscle fibers.
... Thus, training strategies that emphasize high-load eccentric contractions, to target high mechani-cal tension, may be effective to induce hypertrophy, but the observed muscle damage is not the primary driver of this adaptation. The initial increases in protein synthesis after such protocols likely reflect muscle repair and remodeling processes and should not be mistaken as hypertrophic responses [10]. This notion is supported by the fact that the amount of muscle damage significantly decreases with chronic resistance training and poorly predicts protein synthesis and muscle hypertrophy [24]. ...
... Many patients are affected by unilateral upper limb sports injuries, such as pitcher's shoulder or tennis elbow 1,2) . Physiotherapists recommend performing strength training to treat these disorders; however, excessive strength training can cause muscle damage [3][4][5] . Therefore, it is important to understand muscle fatigue and training programs. ...
Purpose] To evaluate the validity of measurement sites for assessing blood lactic acid levels following unilateral upper-limb exercises. [Participants and Methods] Blood lactic acid levels were measured at the fingertips of both hands in 40 healthy young men (mean age 20.9 ± 2.5 years). Measurements were taken before, immediately after, and at 90-s intervals following unilateral upper-limb exercises involving palmar flexion and dorsiflexion of the non-dominant hand. Exercise load was determined through maximum voluntary contraction testing. [Results] No significant differences were found in the average blood lactic acid levels between the fingers at any measurement time point. The peak blood lactic acid level occurred approximately 90 s earlier in the motor limb than in the non-motor limb. [Conclusion] This study found no significant difference in blood lactic acid levels between the motor and non-motor limbs when using fingertip measurements during unilateral upper-limb exercises. Therefore, either fingertip may be a suitable measurement site. However, because the peak lactic acid level in the non-motor limb was delayed by around 90 s, the timing of peak muscle fatigue evaluation in the non-motor limb should be considered.
... Despite EIMD being associated with increased MPS rates under various RET modalities (130), the increased MPS observed in the early stages of resistance exercise appears primarily directed toward tissue repair/remodeling subsequent to muscle damage rather than contributing to skeletal muscle hypertrophy (143). Therefore, although EIMD following a novel bout of RET increases MPS, this increase is unlikely to significantly contribute to increases in muscle mass, especially in exercise-naive individuals. ...
High-load resistance exercise (>60% of 1-repetition maximum) is a well-known stimulus to enhance skeletal muscle hypertrophy with chronic training. However, studies have intriguingly shown that low-load resistance exercise training (RET) (≤60% of 1-repetition maximum) can lead to similar increases in skeletal muscle hypertrophy as compared to high-load RET. This has raised questions about the underlying mechanisms for eliciting the hypertrophic response with low-load RET. A key characteristic of low-load RET is performing resistance exercise to, or close to, task failure, thereby inducing muscle fatigue. The primary aim of this evidence-based narrative review is to explore whether muscle fatigue may act as an indirect or direct mechanism contributing to skeletal muscle hypertrophy during low-load RET. It has been proposed that muscle fatigue could indirectly stimulate muscle hypertrophy through increased muscle fibre recruitment, mechanical tension, ultrastructural muscle damage, the secretion of anabolic hormones, and/or alterations in the expression of specific proteins involved in muscle mass regulation (e.g., myostatin). Alternatively, it has been proposed that fatigue could directly stimulate muscle hypertrophy through the accumulation of metabolic by-products (e.g., lactate), and/or inflammation and oxidative stress. This review summarizes the existing literature eluding to the role of muscle fatigue as a stimulus for low-load RET-induced muscle hypertrophy and provides suggested avenues for future research to elucidate how muscle fatigue could mediate skeletal muscle hypertrophy.
... To ensure that swelling in the muscles from training did not obscure MT results, images were obtained at least 72 hours after exercise/training sessions both in the pre-and postintervention assessment. This is consistent with research showing that acute increases in MT return to baseline within 48 hours following a RT session (18) (19) and that muscle damage is minimal after repeated exposure to the same exercise stimulus over time (20) (21). To further ensure accuracy of measurements, 3 successive images were obtained for each site and then averaged to obtain a final value. ...
... Notably, 60.5% of respondents cited increasing muscular volume as the primary reason, consistent with the belief that muscle hypertrophy is crucial for athletic performance (Schoenfeld, 2010). Another 28.9% relied on supplements due to difficulty preparing healthy food at home, using them to enhance muscular strength, a critical component of many sports (Rawson & Volek, 2003;Damas et al., 2016). A oneway ANOVA revealed significant differences in reasons for supplement usage [F(3, 34) = 7.12, p = 0.001], with increasing muscular volume and strength being the most frequently cited reasons. ...
Background: The indiscriminate use of dietary supplements among athletes poses significant risks, highlighting the need for awareness and education on the potential dangers associated with supplement misuse. Objective: To emphasize the importance of providing athletes with in-depth information on the risks of supplement misuse, including potential side effects, medication interactions, and the lack of regulation in supplement production. Method: This cross-sectional study employed stratified random sampling to recruit 204 athletes from Damascus, Syria. A pilot-tested online survey instrument captured demographic characteristics, athletic background, supplement use habits, and motivations. A standardized physical fitness assessment protocol evaluated cardiovascular endurance, muscular strength, and flexibility. Descriptive statistics, inferential statistics, and multivariate analysis examined relationships between physical fitness, nutritional practices, and athletic performance. Rigorous quality control measures ensured data reliability, including pilot testing, data cleaning, and strategies to minimize response bias and errors. Results: Through evidence-driven education, athletes and the general public can cultivate a discerning understanding of dietary supplements, thereby empowering informed decision-making amidst the vast and complex landscape of available products. Conclusion: The dissemination of technical information through educational campaigns is crucial in fostering a culture of informed decision-making within the sports community. By integrating evidence-based research with practical guidance, governmental and non-governmental organizations can empower individuals with the critical competencies required to make informed decisions about dietary supplement use in sports, ultimately promoting safe and effective athletic performance.
... Metabolic stress, resulting from prolonged time under tension and higher repetitions, leads to muscle growth through the accumulation of metabolites, cellular swelling, hypoxia, and hormonal responses [9,10]. Muscle damage, caused by repetitive stretching and shortening during training, played a minor role in early adaptation [11]. ...
This study aimed to investigate the regional hypertrophic effects of two different once-weekly resistance training programs on the quadriceps muscle. Eighteen untrained men (Age: 21.1±0.5 years, Height: 174.1±5.3 cm, Body weight: 68.8±11.3 kg) with no prior resistance training experience were recruited. Participants were randomly assigned to one of two once-weekly training programs: a Mechanical Tension program (TN) or a Mechanical Tension with Metabolic Stress program (TS), both progressively designed over 6 weeks. Quadriceps muscle cross-sectional areas (QCSA) were measured using magnetic resonance imaging (MRI) at three regions—proximal, middle, and distal—before and after training. The finding demonstrated QCSA significantly increased in the proximal region (∆9.97%, ES = Moderate, and ∆8.9%, ES = Moderate), middle region (∆8.19%, ES = Moderate, and ∆8.42%, ES = Moderate), and distal region (∆7.73%, ES = Moderate, and ∆7.76%, ES = Moderate) for the TN and TS groups, respectively. Maximum strength also significantly increased in both group (∆26.83% in TS and ∆19.82% in TN with ES = Large). Additionally, strong to very strong positive correlations were found among the different regions (r = 0.82–0.94, p = 0.000), which may suggest that measuring a single region could be sufficient for those with budgetary constraints. In conclusion, both training programs effectively induced quadriceps hypertrophy, as well as resulting in increased maximum strength, in untrained participants, highlighting the effectiveness of one-weekly training in promoting muscle growth. Additionally, the knee extension exercise demonstrated the ability to induce relatively uniform hypertrophy across all quadriceps regions.
... We included the studies that met the following criteria in the analysis: (1) examined the effect of R T under intermittent terrestrial or simulated hypoxia for at least 3 weeks (Damas et al., 2016) on strength development (via 1RM) in healthy individuals between 18 and 65 years of age using a randomised design; (2) included a normoxic control group; (3) were published in English-language peerreviewed journals; and (4) provided information about outcomes both at baseline and post-study. Research studies were excluded if they (1) were not original investigations published in full; (2) did not specify the evaluation procedure of the variable selected for analysis (1RM); (3) applied hypoxia via local techniques, such as blood flow restriction; (4) did not provide or specify numerical or graphic data; and (5) examined only the acute effects of interventions. ...
A systematic review and meta-analysis were conducted focused on the impact of specific methodological prescription variables in resistance training (RT) programming on muscle strength under hypoxic conditions. Searches of Pubmed-Medline, Web of Science, Sport Discuss and the Cochrane Library compared the effect of RT on strength development under hypoxic (RTH) vs. Normoxic (RTN) conditions through the 1-repetition maximum (1RM) test. Apart from the overall meta-analysis, several RT methodological prescription variables available in the included studies (set end point, total weekly training volume, type of exercise, region of the body measured or type of routine) were analysed. Thirteen studies met the inclusion criteria. The overall analyses showed trivial differences in 1RM favouring RTH over RTN (SMD = 0.18 [CI: 0.04; 0.31]; p = 0.030). Sub-analyses revealed that a RT programme of a non-full-body routine, including 9 or more sets per exercise/week of multi-joint exercises performed to non-failure, favoured RTH for enhancing 1RM (p < 0.10). In conclusion, the evidence ratified a trivial benefit of RTH
over RTN for muscle strength gains after a RT period. However, the handling of specific RT methodological prescription variables can slightly improve strength development outcomes in hypoxia.
... The exercise stimulus may not have sufficiently stimulated muscle protein catabolism given that we studied a trained population , and/or alternative mass spectrometry-based assessments of 3MH may be more appropriate to detect subtle differences in this outcome (Cegielski et al., 2021). Regardless, changes in myofibrillar protein synthesis are generally more predictive of muscle hypertrophy particularly when assessed under free-living conditions (Abou Sawan et al., 2022;Damas et al., 2016) and therefore targeting nutrition strategies to attenuate myofibrillar protein catabolism may be of lower practical relevance for athletes aiming to enhance gains in lean body mass with resistance exercise training. ...
Marine-derived proteins, such as blue whiting-derived protein hydrolysates (BWPH), represent high-quality sources of dietary protein, but their ability to support postexercise anabolism is not established. The impact of BWPH on whole-body anabolism was compared with an isonitrogenous whey protein isolate (WPI) and nonessential amino acid (NEAA) control in 10 trained young males (31 ± 4 years) who, on three separate visits, performed a session of whole-body resistance exercise and then consumed, in randomized crossover fashion, BWPH, WPI, or NEAA (0.33 g/kg; 19, 33, and 0 mg/kg leucine, respectively) with L-[1-13 C]leucine. Breath, blood, and urine samples were collected for 6-hr postprandial to assess dietary leucine oxidation, amino acid (AA) concentrations, and 3-methylhistidine: creatinine ratio. Peak and area under the curve concentrations for leucine, branched-chain amino acids, and essential amino acids were greater in WPI compared with BWPH (all p < .05) but with no differences in time to peak concentration. Total oxidation reflected leucine intake (WPI > BWPH > NEAA; p < .01), whereas relative oxidation was greater (p < .01) in WPI (28.6 ± 3.6%) compared with NEAA (21.3 ± 4.2%), but not BWPH (28.6 ± 8.8%). Leucine retention, a proxy for whole-body protein synthesis, was greater in WPI (185.6 ± 9.5 μmol/kg) compared with BWPH (109.3 ± 14.1 μmol/kg) and NEAA (5.74 ± 0.30 μmol/kg; both p < .01), with BWPH being greater than NEAA (p < .01). Urinary 3-methylhistidine: creatinine ratio did not differ between conditions. Both WPI and BWPH produced essential aminoacidemia and supported whole-body anabolism after resistance exercise, but a higher intake of BWPH to better approximate the leucine and EAA content of WPI may be needed to produce an equivalent anabolic response.
... Just 1 session of resistance training can attenuate disuse muscle atrophy during bed rest in older adults [24]. Moreover, A single bout of progressive resistance training can increase the muscle protein anabolic response in older adults [25,26], and muscle protein synthesis has been shown to correlate with increased skeletal muscle thickness [24] and myofiber CSA [27]. Exercise, particularly progressive strength training, appears to mitigate disuse-induced muscle atrophy and may delay the onset or progression of sarcopenia, potentially reducing healthcare costs and enhancing the quality of life for the older population [24]. ...
Background
Hospitalization exacerbates sarcopenia and physical dysfunction in older adults. Whether tailored inpatient exercise prevents acute sarcopenia is unknown. This study aimed to examine the effect of a multicomponent exercise programme on muscle and physical function in hospitalized older adults. We hypothesized that participation in a brief tailored exercise regimen (i.e., 3–5 days) would attenuate muscle function and structure changes compared with usual hospital care alone.
Methods
This randomized clinical trial with blinded outcome assessment was conducted from May 2018 to April 2021 at Hospital Universitario de Navarra, Spain. Participants were 130 patients aged 75 years and older admitted to an acute care geriatric unit. Patients were randomized to a tailored 3‐ to 5‐day exercise programme (n = 64) or usual hospital care (control, n = 66) consisting of physical therapy if needed. The coprimary endpoints were between‐group differences in changes in short physical performance battery (SPPB) score and usual gait velocity from hospital admission to discharge. Secondary endpoints included changes in rectus femoris echo intensity, cross‐sectional area, thickness and subcutaneous and intramuscular fat by ultrasound.
Results
Among 130 randomized patients (mean [SD] age, 87.7 [4.6] years; 57 [44%] women), the exercise group increased their mean SPPB score by 0.98 points (95% CI, 0.28–1.69 points) and gait velocity by 0.09 m/s (95% CI, 0.03–0.15 m/s) more than controls (both p < 0.01). No between‐group differences were observed in any ultrasound muscle outcomes. There were no study‐related adverse events.
Conclusions
Three to 5 days of tailored multicomponent exercise provided functional benefits but did not alter muscle or fat architecture compared with usual hospital care alone among vulnerable older patients. Brief exercise may help prevent acute sarcopenia during hospitalization.
Trial Registration
ClinicalTrials.gov identifier: NCT04600453
... When paired conceptually with the lack of a consistent, independent effect of frequency in the present meta-analysis, multiple potential explanations exist. These include: i) the MPS timelines reported in acute research do not necessarily represent hypertrophic effects, perhaps in part or entirely related to muscle damage repair confounding MPS elevations (115); ii) the collective training status of the included participants was not sufficiently advanced, resulting in an extended anabolism period post-training, which may have obscured the beneficial effects of higher frequency; ...
Background: Weekly set volume and frequency are used to manipulate resistance training (RT) dosage. Previous research has identified higher weekly set volume as enhancing muscle hypertrophy and strength gains, but the nature of the dose-response relationship still needs to be investigated. Mixed evidence exists regarding the effects of higher weekly frequency. Objective: Before meta-analyzing the volume and frequency research, all contributing RT sets were classified as direct or indirect, depending on their specificity to the hypertrophy/strength measurement. Then, weekly set volume/frequency for indirect sets was quantified as 1 for 'total,' 0.5 for 'fractional,' and 0 for 'direct.' A series of multi-level meta-regressions were performed for muscle hypertrophy and strength, utilizing 67 total studies of 2,058 participants. All models were adjusted for the duration of the intervention and training status. Results: The relative evidence for the 'fractional' quantification method was strongest; therefore, this quantification method was used for the primary meta-regression models. The posterior probability of the marginal slope exceeding zero for the effect of volume on both hypertrophy and strength was 100%, indicating that gains in muscle size and strength increase as volume increases. However, both best fit models suggest diminishing returns, with the diminishing returns for strength being considerably more pronounced. The posterior probability of the marginal slope exceeding zero for frequency's effect on hypertrophy was less than 100%, indicating compatibility with negligible effects. In contrast, the posterior probability for strength was 100%, suggesting strength gains increase with increasing frequency, albeit with diminishing returns. Conclusions: Distinguishing between direct and indirect sets appears essential for predicting adaptations to a given RT protocol, such as using the 'fractional' quantification method. This method's dose-response models revealed that volume and frequency have unique dose-response relationships with each hypertrophy and strength gain. The dose-response relationship between volume and hypertrophy appears to differ from that with strength, with the latter exhibiting more pronounced diminishing returns. The dose-response relationship between frequency and hypertrophy appears to differ from that with strength, as only the latter exhibits consistently identifiable effects.
... At the end of each workout, the training supervisor personally handed out the supplement, instructing participants to dissolve the whey powder in about 0.5 L of water and consume it within 30 min. Standardization of protein intake during early post-workout recovery was deemed important because consuming protein in this period influences muscle protein synthesis [59,60], and post-workout changes in muscle protein synthesis are linked to the degree of muscle hypertrophy that manifests as a result of several weeks RT [61]. ...
Background: This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM), and influencing cardiorespiratory fitness (VO2max) in Vit-D-deficient middle-aged healthy men. Methods: Participants (n = 28) were quasi-randomly assigned to one of two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) during participation in a 12-week supervised RT program. Results: During the intervention, serum Vit-D concentrations increased 2.6-fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. Conclusions: In conclusion, in healthy Vit-D-insufficient middle-aged men engaged in resistance training, Vit-D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM, or decreases in fat mass and fat percentage, and does not affect cardiorespiratory fitness.
... At the end of each workout, the training supervisor personally handed out the supplement, instructing participants to dissolve the whey powder in about 0.5 L of water and consume it within 30 min. Standardization of protein intake during early post-workout recovery was deemed important because consuming protein in this period influences muscle protein synthesis [56,57], and postworkout changes in muscle protein synthesis are linked to the degree of muscle hypertrophy that manifests as a result of several weeks RT [58]. ...
This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM) and influencing cardiorespiratory fitness (VO2max) in Vit-D insufficient middle-aged healthy men. Participants (n = 28) were quasi‐randomly assigned to one of the two groups, which, in a double‐blind manner, supplemented their diet daily with either Vit‐D (8000 IU; VD) or placebo (PLC) during participation in a 12‐week supervised RT program. During the intervention, serum Vit‐D concentrations increased 2.6‐fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. In conclusion, in healthy Vit‐D insufficient middle-aged men engaged in resistance training, Vit‐D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM or decreases in fat mass and fat percentage and does not affect cardiorespiratory fitness.
... This is likely caused by the increased demand for AAs following whole body compared to isolated leg-based training, with the 20 g protein dose potentially not supplying enough AAs to meet the demands of the greater number of muscles utilised in whole body RE. It should also be noted that the adults recruited were untrained, which may also contribute to the observed anabolic response, which is known to be attenuated in trained individuals (100). However, these explanations are speculative, and there is currently no study directly comparing MPS responses to different protein doses following different types of RE. ...
Protein nutrition is critical for the maintenance of skeletal muscle mass across the lifecourse and for the growth of muscle in response to resistance exercise – both acting via the stimulation of protein synthesis. The transient anabolic response to protein feeding may vary in magnitude and duration, depending on, e.g., timing, dose, amino acid composition and delivery mode, which are in turn influenced by physical activity and age. This review aims to: (i) summarise the fundamental metabolic responses of muscle to protein feeding, (ii) discuss key variables regulating muscle anabolic responses to protein feeding, and (iii) explore how these variables can be optimised for muscle anabolism in response to physical activity and ageing.
... When amino acids are consumed, MPS can exceed MPB [10]. While MPS is associated with hypertrophy, it also aids in the remodeling of contractile and structural proteins [11]. MPS could be affected by a vegetarian diet due to the lower protein bioavailability and lower protein intake that are typically seen in vegetarian diets [8,9]. ...
It is unclear if following a vegetarian diet affects muscle recovery after exercise-induced muscle damage (EIMD). Sixteen vegetarians (VEG) and sixteen mixed dieters (MIX) performed a vertical jump, quadriceps femoris maximal isometric, and isokinetic concentric strength tests prior to and five days following the EIMD protocol. The quadriceps muscle was injured by performing eccentric contractions. Diet: MIX consumed more g/kg of animal protein (p < 0.001) and EAA (p < 0.05) except for isoleucine. VEG consumed more plant protein (p = 0.001). Isometric strength: MIX recovered post-day 2, VEG recovered post-day 4 (group (p = 0.07), time (p < 0.001)). Concentric contractions at 60 degrees per second: Both recovered post-day 1 (group (p = 0.27), time (p = 0.05)); 180 degrees per second: MIX recovered post-day 2, VEG recovered post-day 5 (group (p = 0.10), time (p < 0.001)); and 240 degrees per second: MIX recovered post-day 1, VEG did not recover by post-day 5 (group (p = 0.01), time (p < 0.001)). Vertical jump: Both recovered post-day 3 (group (p = 0.45), time (p < 0.001)). MIX recovered isometric strength 2 days faster, concentric strength was up to 5 days faster, and soreness was 1–4 days faster when compared to VEG. Both groups had similar recovery time for power.
... RT also serves as a robust stimulus to increase MPS, which works additively with protein feeding to stimulate MPS beyond either stimulus alone (Biolo et al., 1995(Biolo et al., , 1997. It can be problematic to infer changes in muscle mass from acute MPS studies (Witard et al., 2021); however, Damas and colleagues have elegantly shown a time course-dependent relationship between the acute response of MPS to RT and chronic changes in muscle mass during RT (Damas et al., 2016), which is modified by training status. However, the muscles of older individuals gradually become less sensitive to anabolic stimuli (e.g., exercise and protein nutrition) (Brook et al., 2016;Kumar et al., 2009;Moore et al., 2015), which is an age-related phenomenon known as anabolic resistance and can make maintaining skeletal muscle mass with ageing especially challenging. ...
The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due to the presence of ‘anabolic resistance’, resulting in muscle loss. Sarcopenia can be transiently but markedly accelerated through periods of muscle disuse‐induced (i.e., unloading) atrophy due to reduced physical activity, sickness, immobilisation or hospitalisation. Periods of disuse are detrimental to older adults' overall quality of life and substantially increase their risk of falls, physical and social dependence, and early mortality. Disuse events induce skeletal muscle atrophy through various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis and mitochondrial dysfunction, all of which tip the scales in favour of a negative net protein balance and subsequent muscle loss. Concerningly, recovery from disuse atrophy is more difficult for older adults than their younger counterparts. Resistance training (RT) is a potent anabolic stimulus that can robustly stimulate muscle protein synthesis and mitigate muscle losses in older adults when implemented before, during and following unloading. RT may take the form of traditional weightlifting‐focused RT, bodyweight training and lower‐ and higher‐load RT. When combined with sufficient dietary protein, RT can accelerate older adults' recovery from a disuse event, mitigate frailty and improve mobility; however, few older adults regularly participate in RT. A feasible and practical approach to improving the accessibility and acceptability of RT is through the use of resistance bands. Moving forward, RT must be prescribed to older adults to mitigate the negative consequences of disuse atrophy.
... From a physiological point of view, the micro-injuries in the Z band induced by resistance training occur in the first week of training, and protein synthesis initially serves to repair these damages. However, from the third week of training, the microlesions are attenuated, however, with protein synthesis causing an increase in sarcomeres in series (muscle hypertrophy) (Damas et al., 2016). Perhaps, this adaptation explains why DOMS is usually caused in the first few sessions. ...
The aim of the study was to investigate four treatments for the recovery of delayed onset muscle soreness (DOMS). DOMS was induced in 56 women forced by the "Drop Set" system and they were divided into four treatment groups: home, massage, proprioceptive neuromuscular facilitation (PNF) and passive stretching. The volunteers answered two pain scales: a numerical scale and a visual analogue scale (VAS) in five stages: 0 h, 24 h, 48 h, 72 h, 96 h and 120 h, before each treatment session. The statistical analysis between the scales and at the different times was carried out using one-way analysis of variance; and the comparison between the groups at the same time was carried out using repeated measures analysis of variance, followed by the Tukey-Kramer post-test. There was no significant difference between the pain measures of the scales. Massage had the lowest pain intensity at 24 and 48 hours compared to the other treatments. Massage is the best method for treating DOMS and passive stretching is the worst. The pain scales are equivalent to each other and could be relevant tools for monitoring recovery from intense physical training.
... This adaptive response, e.g. reflected in reduced symptoms of exercise-induced muscle damage and soreness [84,85], underscores the increased resilience and likely enhanced repair and regenerative capacity of trained muscle. This phenomenon is known as the "repeated bout effect" [86]. ...
Skeletal muscle plasticity enables an enormous potential to adapt to various internal and external stimuli and perturbations. Most notably, changes in contractile activity evoke a massive remodeling of biochemical, metabolic and force-generating properties. In recent years, a large number of signals, sensors, regulators and effectors have been implicated in these adaptive processes. Nevertheless, our understanding of the molecular underpinnings of training adaptation remains rudimentary. Specifically, the mechanisms that underlie signal integration, output coordination, functional redundancy and other complex traits of muscle adaptation are unknown. In fact, it is even unclear how stimulus-dependent specification is brought about in endurance or resistance exercise. In this review, we will provide an overview on the events that describe the acute perturbations in single endurance and resistance exercise bouts. Furthermore, we will provide insights into the molecular principles of long-term training adaptation. Finally, current gaps in knowledge will be identified, and strategies for a multi-omic and -cellular analyses of the molecular mechanisms of skeletal muscle plasticity that are engaged in individual, acute exercise bouts and chronic training adaptation discussed.
... A second factor that determines the accumulation of myofibrillar proteins within muscle is the rate of protein degradation [56]. Proteoasomal degradation of myofibrillar proteins is rapidly activated after acute RT [57] and is increased when myofibrillar damage is more extensive, such as at the beginning of a RT period [58,59]. Lastly, calf muscles have a higher atrophy potential compared to other muscles of the lower limb, and it has been argued that calf muscles have a higher proteasomal capacity [13]. ...
Objectives
Whether low-load resistance training (RT) without muscle failure, with or without blood flow restriction (BFR), is sufficient to increase strength and muscle growth of calf muscles in trained individuals is still unclear. This study aimed to compare the effects of low-intensity BFR RT vs. traditional low-intensity RT (noBFR) with moderate training volume on strength and circumference.
Methods
We designed a parallel, randomized controlled trial including 36 RT-trained participants (BFR: 7 females, 32.9 ± 8.8 years, 11 males, 28.4 ± 3.6 years; noBFR; 8 females, 29.6 ± 3.4 years; 10 males, 28.6 ± 4.9 years) who underwent eight weeks of twice-weekly low-load RT with a total of 16 RT sets (30 % of one-repetition maximum [1RM]). RT consisted of bilateral calf raises and seated unilateral calf raises, each conducted with 4 sets (30, 15, 15, 15 repetitions not to failure) of either BFR or noBFR. Outcome measures included calf circumference (CC), leg stiffness (LS), and various strength tests (seated and standing calf raise 1RM, isokinetic strength of plantar- and dorsiflexion).
Results
There were no significant interactions or group effects for most measures. Both groups showed significant improvements in seated calf raise strength (p=0.046, η ² p=0.17). Pairwise comparisons indicated moderate to large effect sizes for strength improvements (standardized mean differences: 0.35–1.11), but no changes in calf circumference were observed in either group.
Conclusions
Low-load RT with and without BFR are useful to increase strength without necessarily affecting hypertrophy. Low-intensity BFR training did not confer additional benefits over traditional low-intensity RT for calf muscle strength or circumference, questioning its general advantage under such conditions.
... S-BIS and ultrasound are useful in assessing the immediate effectiveness of resistance training. MT exhibits a temporary increase following resistance training (Fig. 7) because of "edema-induced muscle swelling," a phenomenon that occurs due to swelling both inside and outside the muscle fibers resulting from muscle damage with resistance training 29,30) . Muscle swelling is an important effect index observed at the beginning of the training session and served as an indirect marker of myofibrillar protein synthesis 31) . ...
A decline in muscle strength is a key factor responsible for physical dysfunction in older individuals. Both loss of muscle quantity and quality are associated with muscle strength decline. While the gold standard method for evaluating muscle mass and quality is magnetic resonance imaging, it is not suitable for clinical settings because of the measurement and analysis costs. Bioelectrical impedance analysis (BIA) and B-mode ultrasonography are clinically useful alternatives for skeletal muscle assessment owing to their feasibility and noninvasiveness. The recent advancements in the techniques for BIA and ultrasonography have improved their accuracy in assessing skeletal muscle quantity and quality, making them useful in detecting age-related and disease-specific alterations. This review comprehensively analyzes the advantages of using BIA and ultrasound imaging for assessing skeletal muscle quantity and quality and detecting muscle degeneration. We summarize the recent findings regarding age-related changes in muscle characteristics and the associations of muscle degeneration with physical dysfunction in patients with knee osteoarthritis. Furthermore, we discuss the clinical application of skeletal muscle assessment using BIA and ultrasound for evaluating training effects and exercise prescription.
... This reason may be explained by neural coordination or some kinds of change in muscle contraction properties. Muscle morphological adaptation such as muscle hypertrophy is observable after 6-wk resistance training intervention because protein synthesis would be required to repair and attenuate muscle damage during the early phase of training (25,26). Since resistance training was not performed in the current study, muscle damage, repair, and hypertrophy did not occur. ...
Alaska pollack protein (APP), has been reported as a protein source that can enhance muscle hypertrophy more than other protein sources in animal studies. This study aimed to examine the effects of APP ingestion on muscle quantity and quality in young adults. Fifty-five young college students were assigned to two groups: APP and placebo (whey protein: WP) groups, and instructed to ingest 4.5 g of each protein in addition to daily meals, and to maintain their usual daily physical activities for 3 mo. Twenty-one and 23 students completed the intervention and were analyzed in APP and WP groups, respectively. The maximum knee extension torque significantly increased in both groups during the intervention. The motor unit discharge rate, which is an indicator of activation, for a given force level significantly decreased in both groups during the intervention, but its decrease in the APP group was significantly greater than in the WP group. Echo intensity of the vastus lateralis evaluated by ultrasound images significantly decreased in both groups. The muscle thickness and skeletal muscle mass did not change. Small amount of additional APP intake induces greater effects on neural activation than WP, suggesting the greater neural economy of generation of force.
... As previously described (17) To help ensure that swelling in the muscles from training did not obscure muscle thickness results, images were obtained at least 48 hours after the training sessions in both the pre-and post-study assessments. This is consistent with research showing that acute increases in muscle thickness return to baseline within 48 hours following a RT session (20,21) and that muscle damage is minimal after repeated exposure to the same exercise stimulus over time (22,23). To further ensure accuracy of measurements, three successive images were obtained for each site and then averaged to obtain a final value. ...
... Since, EIMD causes elevated inflammatory response, increase in insulin -like growth factor-1, causing intracellular water content to rise which is suggestive of hypertrophy of skeletal muscles. Also, there is muscle damage which results in a significant reduction in the performance of skeletal muscle (Byrne et al., 2004) and prolonged decrease in DOMS, MVIC strength, ROM and inflation of creatine kinase and other muscle proteins in the blood (Damas et al., 2016). Unaccustomed exercise is closely associated with a significant strength loss that ameliorates slowly over 2-3 weeks (Souron et al., 2018). ...
... However, tracking the temporal pattern of change in muscle ultrastructure after a bout of EIMD would require multiple muscle biopsies, a highly invasive procedure. As a proxy for EIMD, MVC is regarded as a reliable technique to track muscle recovery from damaging exercise (Chalchat et al. 2022;Damas et al. 2016;Morton et al. 2005;Nosaka and Clarkson 1995;Peake et al. 2017). However, we found that the level of thiol-oxidised albumin remained elevated for longer than the duration of the MVC impairment and for this reason thiol-oxidised albumin may better track recovery from EIMD. ...
Purpose
Exercise-induced muscle damage (EIMD) results in the generation of reactive oxygen species (ROS), but little is known about the temporal profile of change in ROS post-EIMD and how ROS levels relate to the onset of and recovery from EIMD. Our primary aim was to examine the effect of EIMD on the pattern of change in the blood level of thiol-oxidised albumin, a marker of oxidative stress.
Methods
Seven male participants were subjected on separate days to eccentric muscle contraction to cause EIMD or a no-exercise condition. After each session, the participants collected daily dried blood spots to measure thiol-oxidised albumin and returned to the laboratory every 2 days for the assessment of indirect markers of EIMD, namely maximal voluntary contraction (MVC), delayed onset muscle soreness (DOMS), creatine kinase (CK), and myoglobin.
Results
Eccentric exercise resulted in a significant decrease in MVC and increase in DOMS, CK, myoglobin, and thiol-oxidised albumin with the latter reaching above baseline level within 24–48 h post-exercise. All the markers of EIMD returned to baseline level within 6 days post-exercise, but not the level of thiol-oxidised albumin which remained elevated for 10 days after exercise. There was a moderate correlation between changes in thiol-oxidised albumin and DOMS, but no significant relationship between any other markers of muscle damage.
Conclusion
The levels of thiol-oxidised albumin increase in response to EIMD and remain elevated for several days post-exercise. The temporal pattern of change in the level of thiol-oxidised albumin suggests that this may be a useful biomarker of muscle repair post-EIMD.
... Finally, the limited 18 training sessions warrants further discussion. Indeed, evidence from past shorter-term interventions suggests that 14-21 training sessions is minimally needed to reliably detect myofiber hypertrophy (Goreham et al., 1999;Damas et al., 2016;Mesquita et al., 2023), and this certainly warrants a longer-term intervention with the current training protocols. However, despite the limited training duration, interesting differences between protocols were Changes in the cross-sectional area (fCSA), myofibrillar and non-myofibrillar area of type I + II fibers [(A-C), respectively], ratio of the myofibrillar and non-myofibrillar area of fibers type I + II (D) and extracellular space of type I + II fibers (E). ...
Blood flow restriction applied during low-load resistance training (LL-BFR) induces a similar increase in the cross-sectional area of muscle fibers (fCSA) compared to traditional high-load resistance training (HL-RT). However, it is unclear whether LL-BFR leads to differential changes in myofibrillar spacing in muscle fibers and/or extracellular area compared to HL-RT. Therefore, this study aimed to investigate whether the hypertrophy of type I and II fibers induced by LL-BFR or HL-RT is accompanied by differential changes in myofibrillar and non-myofibrillar areas. In addition, we examined if extracellular spacing was differentially affected between these two training protocols. Twenty recreationally active participants were assigned to LL-BFR or HL-RT groups and underwent a 6-week training program. Muscle biopsies were taken before and after the training period. The fCSA of type I and II fibers, the area occupied by myofibrillar and non-myofibrillar components, and extracellular spacing were analyzed using immunohistochemistry techniques. Despite the significant increase in type II and mean (type I + II) fCSA (p < 0.05), there were no significant changes in the proportionality of the myofibrillar and non-myofibrillar areas [∼86% and ∼14%, respectively (p > 0.05)], indicating that initial adaptations to LL-BFR are primarily characterized by conventional hypertrophy rather than disproportionate non-myofibrillar expansion. Additionally, extracellular spacing was not significantly altered between protocols. In summary, our study reveals that LL-BFR, like HL-RT, induces skeletal muscle hypertrophy with proportional changes in the areas occupied by myofibrillar, non-myofibrillar, and extracellular components.
... Similarly, Di Donato et al. [44] demonstrated a significant increase in mitochondrial and myofibrillar protein synthesis 24-28 h postexercise following a higher intensity continuous exercise bout (60% Watt max ) compared to a lower intensity bout (30% Watt max ). Damas et al. [45] observed a significant correlation between myofibrillar protein synthesis and hypertrophy in the early stages of resistance training. However, at 3 weeks, following five resistance-training bouts, muscle hypertrophy was no longer correlated with muscle damage but with protein synthesis. ...
Sarcopenia is a significant health concern primarily affecting old adult individuals, characterized by age-related muscle loss, and decreased strength, power, and endurance. It has profound negative effects on overall health and quality of life, including reduced independence, mobility, and daily activity performance, osteoporosis, increased fall and fracture risks, metabolic issues, and chronic diseases like diabetes and cardiovascular conditions. Preventive strategies typically involve a combination of proper nutrition and regular physical activity. Among strength training exercises, high-intensity interval training (HIIT) stands out as the most effective approach for improving muscle function in older adults with sarcopenia. The current review identifies and summarizes the studies that have examined the effects of HIIT on muscle strength in older adults as an element of the prevention and treatment of sarcopenia. A systematic search using several computerized databases, namely, MEDLINE/PubMed, Scopus, SPORTDiscus, and Web of Science, was performed on 12 January 2023, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 224 studies were initially retrieved. A total of five studies met the selection criteria. HIIT training shows improvements in body composition and functional and cardiorespi-ratory capacity, has benefits on muscle strength, increases muscle quality and architecture, and is associated with muscle hypertrophy in healthy older adults. Nonetheless, given the shortcomings affecting primary research in terms of the limited number of studies and the high risk of bias, further research is warranted.
... Whether closer proximities-to-failure during RT always promote greater muscle hypertrophy, however, is contentious. For example, RT sets to momentary muscular failure may incur high levels of i) neuromuscular fatigue that impairs the stimulus acheived within a RT session , and ii) muscle damage that compromises protein synthesis directed towards muscle hypertrophy (Damas et al., 2016). Therefore, prescribing RT with a repetitions-in-reserve (RIR) scale to terminate sets close to, but not at momentary muscular failure has become common Zourdos et al., 2016). ...
This study examined the influence of resistance training (RT) proximity-to-failure, determined by repeti- tions-in-reserve (RIR), on quadriceps hypertrophy and neuromuscular fatigue. Resistance-trained males (n = 12) and females (n = 6) completed an 8-week intervention involving two RT sessions per week. Lower limbs were randomised to perform the leg press and leg extension exercises either to i) momentary muscular failure (FAIL), or ii) a perceived 2-RIR and 1-RIR, respectively (RIR). Muscle thickness of the quadriceps [rectus femoris (RF) and vastus lateralis (VL)] and acute neuromuscular fatigue (i.e., repetition and lifting velocity loss) were assessed. Data was analysed with Bayesian linear mixed-effect models. Increases in quadriceps thickness (average of RF and VL) from pre- to post-intervention were similar for FAIL [0.181 cm (HDI: 0.119 to 0.243)] and RIR [0.182 cm (HDI: 0.115 to 0.247)]. Between-protocol differences in RF thickness slightly favoured RIR [−0.036 cm (HDI: −0.113 to 0.047)], but VL thickness slightly favoured FAIL [0.033 cm (HDI: −0.046 to 0.116)]. Mean volume was similar across the RT intervention between FAIL and RIR. Lifting velocity and repetition loss were consistently greater for FAIL versus RIR, with the magnitude of difference influenced by the exercise and the stage of the RT intervention.
... Interestingly, changes to MPS after an acute RE bout only poorly correlate with long-term gains in muscle mass [72]. This appears to be the case because the first exercise bouts are associated with a disproportionate amount of muscle damage, and after this muscle damage subsides, correlations between MPS and long-term hypertrophy become remarkably high [73]. It is likely that the early increase in MPS is repair-oriented, while MPS contributes to hypertrophy only in later stages. ...
Understanding the intricate mechanisms governing the cellular response to resistance exercise is paramount for promoting healthy aging. This narrative review explored the age-related alterations in recovery from resistance exercise, focusing on the nuanced aspects of exercise-induced muscle damage in older adults. Due to the limited number of studies in older adults that attempt to delineate age differences in muscle discovery, we delve into the multifaceted cellular influences of chronic low-grade inflammation, modifications in the extracellular matrix, and the role of lipid mediators in shaping the recovery landscape in aging skeletal muscle. From our literature search, it is evident that aged muscle displays delayed, prolonged, and inefficient recovery. These changes can be attributed to anabolic resistance, the stiffening of the extracellular matrix, mitochondrial dysfunction, and unresolved inflammation as well as alterations in satellite cell function. Collectively, these age-related impairments may impact subsequent adaptations to resistance exercise. Insights gleaned from this exploration may inform targeted interventions aimed at enhancing the efficacy of resistance training programs tailored to the specific needs of older adults, ultimately fostering healthy aging and preserving functional independence.
... The repeated bout effect states that with training progression, muscle damage and soreness is attenuated, indicative of training habituation and muscle adaptation to either prevent further damage and/or accelerate repair and regeneration (Damas et al., 2016;Deyhle et al., 2015). This could, for example, be achieved by structural remodeling conferring enhanced resilience against mechanical stress. ...
Skeletal muscle is a highly specialized tissue with pleiotropic functions including motor control and force generation, thermogenesis, storage of amino acids, glucose and lipids, as well as the detoxification of compounds such as kynurenines and ketone bodies. In response to intrinsic or extrinsic perturbations including mechanical and metabolic stress, nutrient composition and availability, or the prevailing hormonal milieu, skeletal muscle demonstrates enormous plasticity. These perturbations of cellular homeostasis (e.g., in response to exercise) elicit a highly coordinated response that involves a complex interplay between multiple signaling
pathways, transcriptional regulators, and effector proteins ultimately leading to muscle adaptation. Endurance training induces a wide range of molecular, cellular, morphological and functional adaptations characterized by increased oxidative capacity, and enhanced uptake, storage and utilization of energy substrates such as glucose and fatty acids, that collectively contribute to improved endurance capacity. The introduction of the Bergström needle to obtain skeletal muscle biopsies in the 1960s was the stimulus for a broader investigation of the cellular and molecular processes in both sedentary and trained humans, revealing substantial insights into the molecular underpinnings of training adaptation (Ekblom, 2017; Lavin et al., 2022). Here, we discuss our current knowledge of the molecular bases of endurance training adaptation.
... Another possibility is that excess swelling resulting from high volume protocols may be mis-interpreted for muscle growth. Although swelling does not appear to accumulate across a training week 19 and is suggested to dissipate 48-72 hours following a training bout, 20 it does seem possible that heightened swelling may be present with high volume training. For example, the study cited by Schoenfeld et al. 3 for their suggestion that acute increases in MT return to baseline within 48 h after an RT session is a paper that cites pilot data (data not presented) to suggest that acute muscle swelling from bench press exercise returns to baseline within 24 hours. ...
Within the resistance training and muscle growth research space, the importance of resistance training volume is often touted as one of, if not, the single most important variable to consider when designing a resistance training intervention, especially as it pertains to resistance trained individuals. Objectives: To examine the literature used to suggest that volume is the primary driver of skeletal muscle growth. Design and Methods: Non-systematic review. Research articles were collected using search terms such as resistance training OR resistance training volume. These terms were combined with AND: quadriceps muscle thickness, OR biceps muscle thickness, and other muscle-site related terms. Results: Studies in resistance trained individuals that suggest a dose-response relationship between resistance training volume and muscle growth have observed a magnitude of muscle growth that is greater than what is typically observed. For example, it may be common to observe a 0.1-0.25 cm increase in quadriceps muscle thickness following an intervention. However, studies have observed changes as high as 0.6-0.72 cm in quadriceps muscle thickness. In addition, there are several investigations demonstrating similar growth between lower and higher volume training protocols in resistance trained individuals. Conclusions: While resistance training volume may very well be one of the more important factors influencing the hyper trophic response in resistance trained individuals, we would suggest that the current evidence is much more ambiguous. Replication of the current findings may be necessary before strong conclusions are drawn. While some threshold of training volume is likely necessary for muscle growth, the current recommendations may exaggerate its importance.
Optimal adaptation to resistance exercise requires maximal rates of myofibrillar protein synthesis (MyoPS), which can be achieved by postexercise consumption of >20 g of protein or ~2 g of the essential amino acid (EAA) leucine. These nutritional recommendations are based on studies in males. The aim of the present study was to compare the postexercise MyoPS response to nutrition in young females. Twenty-eight healthy, females (age: 28±8 y; BMI: 24±3 kg⋅m ² ) received a primed-continuous infusion of L-[ ring- ² H 5 ]-phenylalanine and completed a bout of unilateral resistance exercise before ingesting a drink containing either 1.5 g EAA ( n=10), 15 g ( n=10) or 20 g ( n=8) whey protein, containing 0.6, 1.5, and 2.0 g leucine, respectively. Blood and muscle samples were collected pre- and post-exercise and drink ingestion to assess MyoPS and gene expression. Drink ingestion increased plasma leucine concentrations following 15 and 20 g whey protein compared with 1.5 g EAA ( P<0.0001). Exercise and drink ingestion increased basal (0.060±0.026, 0.063±0.034, 0.051±0.023%·h ⁻¹ ) MyoPS rates between 0-2 h to 0.117±0.028, 0.098±0.051 and 0.116±0.034%·h ⁻¹ ( P<0.0001) and between 2-4 h to 0.110±0.028, 0.074±0.038, and 0.082±0.061%·h ⁻¹ ( P=0.009) for 1.5, 15, and 20 g drinks, respectively, with no differences observed between drinks ( P=0.416). The postexercise changes in muscle mRNA expression of genes involved in protein turnover, substrate utilization, remodeling and inflammation, did not differ between drinks ( P>0.050). Post-exercise MyoPS did not differ following ingestion of 1.5, 15 and 20 g drinks, hence 0.6 g leucine may be sufficient to stimulate post-exercise MyoPS in young females.
Background and Study Aim. High-intensity interval training (HIIT) has become a popular exercise choice for people who have limited time but aim to maximize their workout results. This study aims to compare the impacts of high-intensity running interval training (HIRIT) and high-intensity progressive resistance training (HIPRT) on oxidative stress biomarkers and antioxidant levels in healthy young males. Material and Methods. The study included 30 healthy male adolescents aged 20–23 years who participated in HIRIT and HIPRT interventions over a four-week period. Data were collected by measuring levels of Malondialdehyde (MDA) and Superoxide Dismutase (SOD) as biomarkers of oxidative stress and antioxidants. These measurements were obtained before and after the intervention using Colorimetric Assay Kits. Data analysis was performed using paired sample t-tests and independent sample t-tests with a significance level set at 5%. Results. The results showed a significant decrease in MDA levels in both high-intensity training interventions. However, SOD levels increased significantly only in the high-intensity running interval training group (p ≤ 0.05). Additionally, comparisons between groups revealed a reduction in MDA levels and an increase in SOD levels (p ≤ 0.05). Conclusions. These findings suggest that both high-intensity running interval training and high-intensity progressive resistance training, conducted over a four-week period, are effective in reducing oxidative stress. Additionally, both types of training increase antioxidant levels in healthy young men. However, high-intensity running interval training proved to be more effective in reducing MDA levels and increasing SOD levels.
Skeletal muscle is a highly plastic tissue which can adapt relatively rapidly to a range of stimuli. In response to novel mechanical loading, e.g. unaccustomed resistance exercise, myofibers are disrupted and undergo a period of ultrastructural remodelling to regain full physiological function, normally within 7 days. The mechanisms which underpin this remodelling are believed to be a combination of cellular processes including UPS/Calpain-mediated degradation, immune cell infiltration and satellite cell proliferation/differentiation. A relatively understudied cellular system which has the potential to be a significant contributing mechanism to repair and recovery is autophagolysosomal system, a cellular process which degrades damaged and dysfunctional cellular components to provide constituent components for the resynthesis of new organelles and cellular structures. This review summarises our current understanding of the autophagolysosomal system in the context of skeletal muscle repair and recovery. In addition, we also provide hypothetical models of how this system may interact with other processes involved in skeletal muscle remodelling and provide avenues for future research to improve our understanding of autophagy in human skeletal muscle.
This study assessed a male competitive powerlifter over a 6-month period that encompassed his pre-contest preparation and post-contest recovery. We conducted the following monthly assessments: multi-frequency bioelectrical impedance analysis (MF-BIA), B-mode ultrasound evaluation of muscle thickness (MT), body circumferences, handgrip strength, vertical jump height, isometric lower body strength, and questionnaires for perceived mood and sleep. The athlete undertook a 3-month pre-contest preparatory period that included an extreme energy-restricted diet intended to sufficiently reduce body mass. This period also included an 8-week pre-contest training regimen with a 10-day taper intended to promote peak strength increases in the target lifts for competition. During the pre-competition period, the athlete experienced rapid and substantial losses of body mass (10.3%), body fat (6.5%) and lean mass (3.3%), the majority of which was regained in the 2-month post-competition recovery phase. The athlete's isometric knee extension strength rose sharply during the initial month of the pre-competition phase (336.4 Nm), followed by consistent declines (299 to 262.2 to 283 Nm) over the next 3 months, eventually returning close to baseline values 2 months post- competition Jump height remained steady in the 3 months in the pre-contest phase but increased (+1.4 cm) in the 2 months post-competition while handgrip strength increased during the months preceding the competition (47.5 kg to 49 kg) but decreased to 42.3 cm post-competition. Overall, the athlete did not seem to have any marked sleep disturbances. The most notable changes in mood parameters were increased tension, anger, and depression immediately preceding the competition.
The present chapter delves into the topic of muscle hypertrophy in detail, focusing on defining what muscle hypertrophy is, the types of hypertrophy, the mechanisms, and the relationship with resistance training, as well as the variables affecting hypertrophy such as nutrition, rest, exercise selection, training volume, and training frequency, among others. The importance of mechanical tension, metabolic stress, and muscle damage as triggers for muscle hypertrophy is emphasized. Various types of muscle hypertrophy are explored, including connective tissue hypertrophy and sarcoplasmic and myofibrillar hypertrophy. The text also delves into how hypertrophy mechanisms relate to resistance training, highlighting the significance of mechanical tension and metabolic stress as stimuli for muscle hypertrophy. In a practical point of view, the text also discusses factors like nutrition and recovery, highlighting the importance of maintaining a positive energy balance and adequate protein intake to promote muscle growth optimally. Training variables such as exercise selection, exercise order, intensity, volume, frequency, and tempo of execution are discussed in detail, outlining their impact on muscle hypertrophy. The text provides a comprehensive overview of muscle hypertrophy, analyzing various factors that influence the ability to increase muscle mass. It offers detailed information on the biological mechanisms, types of hypertrophy, training strategies, and nutritional and recovery considerations necessary to achieve optimal results in terms of muscle hypertrophy.
We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease‐associated muscle atrophy affect these outcomes is needed.
Highlights
What is the central question of this study?
How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation.
What is the main finding and its importance?
This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.
Exercise-induced muscle damage (EIMD) and repeated bout effect (RBE) are widely researched across various populations and at various intensities. Despite the existence of vast literature, there is lack of comparison of low versus submaximal versus maximal intensity required for preconditioning. The aim of the study was to compare the muscle damage and RBE at various intensities of eccentric exercise in active young men. Thirty-six healthy, physically active men were recruited and randomly assigned to three different groups low-high (L-H, n = 12), submaximal-high (M-H, n = 12) and maximal-high (H-H, n = 12). All participants performed 2 exercise bouts separated by 14 days. L-H, M-H and H-H groups performed low (10% of 1RM), moderate (50% of 1RM) and high (90% of 1RM) intensity eccentric exercise for knee extensors, respectively, in the 1st bout followed by high (100% of 1RM) intensity in the second bout. Muscle soreness (SOR), thigh circumference (CIR), maximal voluntary isometric contraction (MVIC), range of motion (ROM) and blood lactate (Bl Lac) were measured before, immediately, at 24 h, at 48 h and at 72 h after exercise. A significant effect of time appeared for MVIC ( ), CIR ( ), ROM ( ) and Bl Lac ( ). The bout × time interaction, as well as bout × time × group interaction was also found significant indicating changes in muscle strength and ROM. Circumference changed significantly with a significant bout × group interaction effect . SOR ( ) was significant between the bouts. Therefore, exhibiting attenuation of muscle damage markers after the second bout. Findings of the present study showed that muscle damage was evident at all three intensities. Moreover, it was greater after moderate and high intensity as compared to low intensity eccentric exercise. RBE was elicited after three intensities indicating their role in preconditioning the muscles of active men.
No studies have reported ground reaction force (GRF) profiles of the repeated depth jump (DJ) protocols commonly used to study exercise-induced muscle damage. Furthermore, while compression garments (CG) may accelerate recovery from exercise-induced muscle damage, any effects on the repeated bout effect are unknown. Therefore, we investigated the GRF profiles of 2 repeated bouts of damage-inducing DJs and the effects of wearing CG for recovery. Nonresistance-trained males randomly received CG (n = 9) or placebo (n = 8) for 72 hours recovery, following 20 × 20 m sprints and 10 × 10 DJs from 0.6 m. Exercise was repeated after 14 days. Using a 3-way (set × bout × group) design, changes in GRF were assessed with analysis of variance and statistical parametric mapping. Jump height, reactive strength, peak, and mean propulsive forces declined between sets ( P < .001). Vertical stiffness, contact time, force at zero velocity, and propulsive duration increased ( P < .05). According to statistical parametric mapping, braking (17%–25% of the movement) and propulsive forces (58%–81%) declined ( P < .05). During the repeated bout, peak propulsive force and duration increased ( P < .05), while mean propulsive force ( P < .05) and GRF from 59% to 73% declined ( P < .001). A repeated bout of DJs differed in propulsive GRF, without changes to the eccentric phase, or effects from CG.
Background
Based on emerging evidence that brief periods of cessation from resistance training (RT) may re-sensitize muscle to anabolic stimuli, we aimed to investigate the effects of a 1-week deload interval at the midpoint of a 9-week RT program on muscular adaptations in resistance-trained individuals.
Methods
Thirty-nine young men ( n = 29) and women ( n = 10) were randomly assigned to 1 of 2 experimental, parallel groups: An experimental group that abstained from RT for 1 week at the midpoint of a 9-week, high-volume RT program (DELOAD) or a traditional training group that performed the same RT program continuously over the study period (TRAD). The lower body routines were directly supervised by the research staff while upper body training was carried out in an unsupervised fashion. Muscle growth outcomes included assessments of muscle thickness along proximal, mid and distal regions of the middle and lateral quadriceps femoris as well as the mid-region of the triceps surae. Adaptions in lower body isometric and dynamic strength, local muscular endurance of the quadriceps, and lower body muscle power were also assessed.
Results
Results indicated no appreciable differences in increases of lower body muscle size, local endurance, and power between groups. Alternatively, TRAD showed greater improvements in both isometric and dynamic lower body strength compared to DELOAD. Additionally, TRAD showed some slight psychological benefits as assessed by the readiness to train questionnaire over DELOAD.
Conclusion
In conclusion, our findings suggest that a 1-week deload period at the midpoint of a 9-week RT program appears to negatively influence measures of lower body muscle strength but has no effect on lower body hypertrophy, power or local muscular endurance.
It has been proposed that skeletal muscle shows signs of resistance training (RT)-induced muscle hypertrophy much earlier (i.e., ~3-4 weeks of RT) than previously thought. We determined if early increases in whole muscle cross-sectional area (CSA) during a period of RT were concomitant with edematous muscle swelling and thus not completely attributable to hypertrophy.
We analyzed vastus lateralis muscle ultrasound CSA images and their respective echo intensities (CSA-USecho) at the beginning (T1), in the 3rd week of RT (T2) and at the end (T3) of a 10-week RT period in ten untrained young men. Functional parameters [training volume (TV = load × reps × sets) and maximal voluntary contraction (MVC)] and muscle damage markers (myoglobin and interleukin-6) were also assessed.
Muscle CSA increased significantly at T2 (~2.7 %) and T3 (~10.4 %) versus T1. Similarly, CSA-USecho increased at T2 (~17.2 %) and T3 (~13.7 %). However, when CSA-USecho was normalized to the increase in muscle CSA, only T2 showed a significantly higher USecho versus T1. Additionally, TV increased at T2 and T3 versus T1, but MVC increased only at T3. Myoglobin and Interleukin-6 were elevated at T2 versus T1, and myoglobin was also higher at T2 versus T3.
We propose that early RT-induced increases in muscle CSA in untrained young individuals are not purely hypertrophy, since there is concomitant edema-induced muscle swelling, probably due to muscle damage, which may account for a large proportion of the increase. Therefore, muscle CSA increases (particularly early in an RT program) should not be labeled as hypertrophy without some concomitant measure of muscle edema/damage.
Resistance exercise training (RET) is widely used to increase muscle mass in athletes and also aged/cachectic populations. However, the time course and metabolic and molecular control of hypertrophy remain poorly defined. Using newly developed deuterium oxide (D2O)-tracer techniques, we investigated the relationship between long-term muscle protein synthesis (MPS) and hypertrophic responses to RET. A total of 10 men (2361 yr) undertook 6 wk of unilateral (1-legged) RET [6 x 8 repetitions, 75% 1 repetition maximum (1-RM) 3/wk], rendering 1 leg untrained (UT) and the contralateral, trained (T). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom percentage; thereafter 50 ml/wk) with regular body water monitoring in saliva via high-temperature conversion elemental analyzer:isotope ratio mass spectrometer. Further bilateral VL muscle biopsies were taken at 3 and 6 wk to temporally quantify MPS via gas chromatography: pyrolysis: isotope ratio mass spectrometer. Expectedly, only the T leg exhibited marked increases in function [i.e., 1-RM/maximal voluntary contraction (60 degrees)] and VL thickness (peaking at 3 wk). Critically, whereas MPS remained unchanged in the UT leg (e.g., similar to 1.35 +/- 0.08%/d), the T leg exhibited increased MPS at 0-3wk(1.6 +/- 0.01%/d), but not at3-6wk(1.29 +/- 0.11%/d); this was reflected by dampened acute mechanistic target of rapamycin complex 1 signaling responses to RET, beyond 3 wk. Therefore, hypertrophic remodeling is most active during the early stages of RET, reflecting longer-term MPS. Moreover, D2O heralds promise for coupling MPS and muscle mass and providing insight into the control of hypertrophy and efficacy of anabolic interventions.
Muscle hypertrophy following resistance training (RT) involves activation of myofibrillar protein synthesis (MPS) to expand the myofibrillar protein pool. The degree of hypertrophy following RT is, however, highly variable and thus we sought to determine the relationship between the acute activation of MPS and RT-induced hypertrophy. We measured MPS and signalling protein activation after the first session of resistance exercise (RE) in untrained men (n = 23) and then examined the relation between MPS with magnetic resonance image determined hypertrophy. To measure MPS, young men (24±1 yr; body mass index = 26.4±0.9 kg•m(2)) underwent a primed constant infusion of L-[ring-(13)C6] phenylalanine to measure MPS at rest, and acutely following their first bout of RE prior to 16 wk of RT. Rates of MPS were increased 235±38% (P<0.001) above rest 60-180 min post-exercise and 184±28% (P = 0.037) 180-360 min post exercise. Quadriceps volume increased 7.9±1.6% (-1.9-24.7%) (P<0.001) after training. There was no correlation between changes in quadriceps muscle volume and acute rates of MPS measured over 1-3 h (r = 0.02), 3-6 h (r = 0.16) or the aggregate 1-6 h post-exercise period (r = 0.10). Hypertrophy after chronic RT was correlated (r = 0.42, P = 0.05) with phosphorylation of 4E-BP1(Thr37/46) at 1 hour post RE. We conclude that acute measures of MPS following an initial exposure to RE in novices are not correlated with muscle hypertrophy following chronic RT.
Quantification of muscle protein synthesis (MPS) remains a cornerstone to understanding the control of muscle mass. Traditional (13)C-amino-acid tracer methodologies necessitate sustained bed-rest and intravenous cannulation(s), restricting studies to ~12h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, ageing and disease while querying the utility of tracer-techniques to predict the long-term efficacy of anabolic/anti-catabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with (13)C tracers and too short to quantify changes in mass. Eight men (22±3.5y) undertook one-legged resistance-exercise over 8-d (4×8-10 repetitions: 80%-1RM every second-day, to yield 'non-exercised' vs. 'exercise' leg-comparisons) with Vastus Lateralis biopsies taken bi-laterally: 0, 2, 4 and 8-days. After day-0 biopsies, participants consumed a D2O bolus (150ml; 70-Atom%); saliva was collected daily. Fractional synthetic rates (FSR) of myofibrillar (MyoPS), sarcoplasmic (SPS) and collagen (CPS) protein-fractions were measured by GC-Pyrolysis-IRMS and TC/EA-IRMS. Body-water initially enriched at 0.16-0.24 APE, decayed at ~0.009%.d-1. In the non-exercised-leg, MyoPS was: 1.45±0.10%.d-1, 1.47±0.06%.d(-1), 1.35±0.07%.d-1 at 0-2, 0-4 and 0-8d respectively (~0.05-0.06%.h-1). MyoPS was greater in the exercised-leg (0-2d 1.97±0.13%.d(-1), 0-4d 1.96±0.15%.d-1; P<0.01, 0-8d 1.79±0.12%.d(-1); P<0.05). CPS was slower than MyoPS, but followed a similar pattern, with the exercised-leg tending to yield greater FSR's (0-2d; 1.14±0.13%.d-1 vs. 1.45±0.15%.d(-1), 0-4d; 1.13±0.07%.d(-1) vs. 1.47±0.18%.d(-1), 0-8d; 1.03±0.09%.d(-1) vs. 1.40±0.11%.d(-1)). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism, and presumably, catabolism alike.
This study investigated the time wise protective effect conferred by two maximal voluntary isometric contractions (2MVCs) at 20° elbow flexion on muscle damage induced by 30 maximal isokinetic (60° s(-1)) eccentric contractions of the elbow flexors (MaxECC). Sixty-five young untrained men were randomly assigned to a control group that did not perform 2MVCs, or one of four experimental groups (n = 13 per group) who performed 2MVCs either immediately (0d), 2 (2d), 4 (4d) or 7 days (7d) before MaxECC. Changes in maximal isokinetic (60° s(-1)) concentric torque (MVC-CON), optimum angle (OA), range of motion, upper arm circumference, muscle soreness, plasma creatine kinase activity and myoglobin concentration, and ultrasound echo-intensity following MaxECC were compared among the groups by a two-way repeated measures ANOVA. No significant changes in any variables were evident following 2MVCs. The 2d and 4d groups showed 16-62 % smaller (P < 0.05) changes in all variables following MaxECC than the control, 0d and 7d groups. The 2d group showed 14-34 % smaller (P < 0.05) changes in all variables except for OA compared with the 4d group. The changes in the variables were similar among the control, 0d and 7d groups. These results show that 2MVCs that were performed between 2 and 4 days before MaxECC attenuated the magnitude of muscle damage, but no such effect was evident if the 2MVCs were performed immediately or 7 days before MaxECC. It is concluded that the protective effect conferred by 2MVCs is relatively short-lived, and there is a window for the effect to be conferred.
Key points
If skeletal muscle fibres are subjected to excessive activation, or stretched whilst contracting, they subsequently display long‐term reductions in their force response, apparently due in part to structural or molecular changes at the triad junction, where excitation of the surface membrane triggers Ca ²⁺ release from the internal Ca ²⁺ store.
The changes appear to be due to excessive or prolonged increases in intracellular Ca ²⁺ levels, which activate Ca ²⁺ ‐dependent proteases known as calpains, but their target proteins are currently unknown.
This study shows that excessive muscle stimulation, or directly raising intracellular Ca ²⁺ levels, causes calpain activation in tandem with proteolysis of junctophilin, a key protein thought to hold the triad junction together.
Proteolysis of junctophilin is also seen in muscle of mice with muscular dystrophy and in cardiac muscle following ischaemic damage.
Proteolysis of junctophilin may be a major factor causing muscle weakness and cardiac dysfunction in a range of circumstances.
Abstract Excessive increases in intracellular [Ca ²⁺ ] in skeletal muscle fibres cause failure of excitation–contraction coupling by disrupting communication between the dihydropyridine receptors in the transverse tubular system and the Ca ²⁺ release channels (RyRs) in the sarcoplasmic reticulum (SR), but the exact mechanism is unknown. Previous work suggested a possible role of Ca ²⁺ ‐dependent proteolysis in this uncoupling process but found no proteolysis of the dihydropyridine receptors, RyRs or triadin. Junctophilin‐1 (JP1; ∼90 kDa) stabilizes close apposition of the transverse tubular system and SR membranes in adult skeletal muscle; its C‐terminal end is embedded in the SR and its N‐terminal associates with the transverse tubular system membrane. Exposure of skeletal muscle homogenates to precisely set [Ca ²⁺ ] revealed that JP1 undergoes Ca ²⁺ ‐dependent proteolysis over the physiological [Ca ²⁺ ] range in tandem with autolytic activation of endogenous μ‐calpain. Cleavage of JP1 occurs close to the C‐terminal, yielding a ∼75 kDa diffusible fragment and a fixed ∼15 kDa fragment. Depolarization‐induced force responses in rat skinned fibres were abolished following 1 min exposure to 40 μ m Ca ²⁺ , with accompanying loss of full‐length JP1. Supraphysiological stimulation of rat skeletal muscle in vitro by repeated tetanic stimulation in 30 m m caffeine also produced marked proteolysis of JP1 (and not RyR1). In dystrophic mdx mice, JP1 proteolysis is seen in limb muscles at 4 and not at 10 weeks of age. Junctophilin‐2 in cardiac and skeletal muscle also undergoes Ca ²⁺ ‐dependent proteolysis, and junctophilin‐2 levels are reduced following cardiac ischaemia–reperfusion. Junctophilin proteolysis may contribute to skeletal muscle weakness and cardiac dysfunction in a range of circumstances.
Exercise-induced muscle damage is an important topic in exercise physiology. However several aspects of our understanding of how muscles respond to highly stressful exercise remain unclear In the first section of this review we address the evidence that exercise can cause muscle damage and inflammation in otherwise healthy human skeletal muscles. We approach this concept by comparing changes in muscle function (i.e., the force-generating capacity) with the degree of leucocyte accumulation in muscle following exercise. In the second section, we explore the cytokine response to 'muscle-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role of the cyclooxygenase enzymes (COX1 and 2). In summary, we propose that muscle damage as evaluated by changes in muscle function is related to leucocyte accumulation in the exercised muscles. 'Extreme' exercise protocols, encompassing unaccustomed maximal eccentric exercise across a large range of motion, generally inflict severe muscle damage, inflammation and prolonged recovery (> 1 week). By contrast, exercise resembling regular athletic training (resistance exercise and downhill running) typically causes mild muscle damage (myofibrillar disruptions) and full recovery normally occurs within a few days. Large variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes in and recovery of muscle force-generating capacity.
This study compared the effect of an initial exercise consisting of either low-intensity eccentric or maximal isometric contractions (ISOs) on protective effect against maximal eccentric contraction (MaxECC)-induced muscle damage.
Untrained young men were placed into one of five groups (n = 13 per group): MaxECC, 10% ECC, 20% ECC, 90° ISO, and 20° ISO. The MaxECC, 10% ECC, and 20% ECC groups performed 30 ECCs of the elbow flexors using a dumbbell equivalent to 100%, 10%, and 20% of maximal voluntary isometric contraction strength, respectively. The 90° ISO and 20° ISO groups performed 30 ISOs at 90° and 20° of elbow flexion, respectively. Three weeks later, all subjects performed 30 MaxECCs with the arm used for the first bout. Changes in maximal voluntary isometric and concentric contraction strength, range of motion, upper arm circumference, plasma creatine kinase and myoglobin concentration, and muscle soreness before and for 5 d after the first and second exercise bouts were compared among groups by a two-way repeated-measure ANOVA.
Changes in all measures after the first bout were smaller (P < 0.05) for 10% ECC, 20% ECC, 90° ISO, and 20° ISO groups compared with MaxECC group, and the changes were smaller (P < 0.05) for 10% ECC and 90° ISO than 20° ISO and 20% ECC groups. When compared with the first bout of MaxECC group, changes in the measures after the second bout were smaller for 20% ECC and 20° ISO groups with greater protective effect evident for 20° ISO group, but the protective effect conferred by these was smaller (P < 0.05) compared with MaxECCs.
These results suggest that there is threshold intensity for ECCs to confer protective effect, and ISOs at a long muscle length provide preconditioning effect.
Cited By (since 1996): 68
Export Date: 10 April 2012
Source: Scopus
Exercise-induced muscle damage (EIMD) occurs primarily from the performance of unaccustomed exercise, and its severity is modulated by the type, intensity, and duration of training. Although concentric and isometric actions contribute to EIMD, the greatest damage to muscle tissue is seen with eccentric exercise, where muscles are forcibly lengthened. Damage can be specific to just a few macromolecules of tissue or result in large tears in the sarcolemma, basal lamina, and supportive connective tissue, and inducing injury to contractile elements and the cytoskeleton. Although EIMD can have detrimental short-term effects on markers of performance and pain, it has been hypothesized that the associated skeletal muscle inflammation and increased protein turnover are necessary for long-term hypertrophic adaptations. A theoretical basis for this belief has been proposed, whereby the structural changes associated with EIMD influence gene expression, resulting in a strengthening of the tissue and thus protection of the muscle against further injury. Other researchers, however, have questioned this hypothesis, noting that hypertrophy can occur in the relative absence of muscle damage. Therefore, the purpose of this article will be twofold: (a) to extensively review the literature and attempt to determine what, if any, role EIMD plays in promoting skeletal muscle hypertrophy and (b) to make applicable recommendations for resistance training program design.
The present study aimed to analyze the magnitude of muscle damage and inflammatory responses induced by eccentric exercise in young (YW) and postmenopausal women (PMW). Seventeen healthy women (nine YW, 23.89 ± 2.03 years; and eight PMW, 51.13 ± 5.08 years) performed five sets of six maximal eccentric actions of the elbow flexors. Changes in isometric strength, range of motion, muscle soreness, and upper-arm circumference were evaluated pre, post, 24, 48, and 72 h following eccentric exercise. Changes in creatine kinase activity, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and prostaglandin E(2) (PGE(2)) were measured pre, 24, 48, and 72 h following eccentric exercise. For intra and inter-group analysis, a two-way repeated measures ANOVA was applied followed by a Tukey's post hoc test. Pearson's correlation was used to analyze the correlations between variables. It was observed no differences between groups for the markers of muscle damage, although significant modifications (p < 0.05) occurred within groups throughout time for all variables. Post menopausal women showed significantly higher values for TNF-α (p < 0.05). Also, IL-6 presented superior pre value for PMW. For YW, IL-6 and IL-10 values increased 72 h post-eccentric exercise compared to pre. Further, IL-10 was higher for YW than PMW 72 h post-eccentric exercise. Significant correlations (p < 0.05) were found between age and soreness, and between age and PGE(2). In conclusion, YW do not have attenuated muscle damage compared to PMW who do not make use of hormonal replacement therapy. In addition, YW have a greater anti-inflammatory response after eccentric exercise compared to PMW.
The purpose of this study was to determine whether an acute bout of high-intensity resistance exercise (RE) would augment integrative mixed muscle and myofibrillar protein fractional synthesis rates (FSRs) when total energy and macronutrient intake was controlled. Twelve healthy young men were studied over 24 hours and performed an acute bout of exhaustive (5 sets until volitional failure of their 85% 1-repetition maximum) unilateral leg press and knee extension exercise, such that one leg was exercised (EX) and the other served as a control (CON). (2)H(2)O (70%) was provided to measure mixed muscle and myofibrillar FSR, and muscle biopsies (vastus lateralis) were collected from the EX and CON legs 16 hours following the RE session. (2)H-labeling of body water over the course of the experiment was 0.32 ± 0.01 mole percent excess. Interestingly, integrative mixed muscle FSR (percent per hour) was similar between the CON (0.76% ± 0.08%) and EX (0.69% ± 0.06%) legs. In contrast, upon determination of myofibrillar FSR, there was an RE effect (EX, 0.94% ± 0.16% vs CON, 0.75% ± 0.08%; P < .05). High-intensity RE without prior training impacts integrative myofibrillar 24-hour FSR, perhaps without altering total responses.
We examined whether a prior bout of eccentric exercise in the elbow flexors provided protection against exercise-induced muscle damage in the contralateral arm. Fifteen males (age 22.7 ± 2.1 years; height 178.6 ± 6.8 cm, mass 75.8 ± 9.3 kg) were randomly assigned to two groups who performed two bouts of 60 eccentric contractions (30°/s) separated by 2 weeks: ipsilateral (n = 7, both bouts performed in the same arm), contralateral (n = 8, one bout performed in each arm). Strength, muscle soreness and resting arm angle (RAA) were measured at baseline and at 1, 24 and 48 h post exercise. Surface electromyography was recorded during both bouts of exercise. The degree of strength loss was attenuated (p < 0.05) in the ipsilateral group after the second bout of eccentric exercise (-22 cf. -3% for bout 1 and 2 at 24 h, respectively). Strength loss following eccentric exercise was also attenuated (p < 0.05) at 24 h in the contralateral group (-30 cf. 13% for bout 1 and 2, respectively). Muscle soreness (≈34 cf 19 mm) and change in RAA (≈5 cf. 3%) were also lower following the second bout of eccentric exercise (p < 0.05), although there was no difference in the overall change in these values between groups. Median frequency (MF) was decreased by 31% between bouts, with no difference between groups. Data support observations that the repeated bout effect transfers to the opposite (untrained) limb. The similar reduction in MF between bouts for the two groups provides evidence for a centrally mediated, neural adaptation.
This study investigated biceps brachii oxygenation and myoelectrical activity during and following maximal eccentric exercise to better understand the repeated-bout effect. Ten men performed two bouts of eccentric exercise (ECC1, ECC2), consisting of 10 sets of 6 maximal lengthening contractions of the elbow flexors separated by 4 wk. Tissue oxygenation index minimum amplitude (TOI(min)), mean and maximum total hemoglobin volume by near-infrared spectroscopy, torque, and surface electromyography root mean square (EMG(RMS)) during exercise were compared between ECC1 and ECC2. Changes in maximal voluntary isometric contraction (MVC) torque, range of motion, plasma creatine kinase activity, muscle soreness, TOI(min), and EMG(RMS) during sustained (10-s) and 30-repeated isometric contraction tasks at 30% (same absolute force) and 100% MVC (same relative force) for 4 days postexercise were compared between ECC1 and ECC2. No significant differences between ECC1 and ECC2 were evident for changes in torque, TOI(min), mean total hemoglobin volume, maximum total hemoglobin volume, and EMG(RMS) during exercise. Smaller (P < 0.05) changes and faster recovery of muscle damage markers were evident following ECC2 than ECC1. During 30% MVC tasks, TOI(min) did not change, but EMG(RMS) increased 1-4 days following ECC1 and ECC2. During 100% MVC tasks, EMG(RMS) did not change, but torque and TOI(min) decreased 1-4 days following ECC1 and ECC2. TOI(min) during 100% MVC tasks and EMG(RMS) during 30% MVC tasks recovered faster (P < 0.05) following ECC2 than ECC1. We conclude that the repeated-bout effect cannot be explained by altered muscle activation or metabolic/hemodynamic changes, and the faster recovery in muscle oxygenation and activation was mainly due to faster recovery of force.
We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression.
Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition.
These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.
While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23-199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age x time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT.
Since little is known about the repeated bout effect of more than two eccentric exercise bouts, this study compared muscle damage responses among four exercise bouts. Fifteen young (21.8 +/- 1.9 years) men performed four bouts of 30 maximal isokinetic eccentric contractions of the elbow flexors every 4 weeks. Maximal voluntary elbow flexion isometric and concentric strength, range of motion at the elbow joint (ROM), upper arm circumference, blood markers of muscle damage, and muscle soreness were measured before and up to 120 h following each bout. Changes in all measures following the second to fourth bouts were significantly (P < 0.05) smaller than those after the first bout. The decreases in strength and ROM immediately after the fourth bout were significantly (P < 0.05) smaller than other bouts. It is concluded that the first bout confers the greatest adaptation, but further adaptation is induced when the exercise is repeated more than three times.
Muscle ultrastructure and contractile properties were examined before and after a single bout of resistance exercise (8 sets of 8 repetitions at 80% of 1 repetition maximum). Eight untrained males performed the concentric (Con) phase of arm-curl exercise with one arm and the eccentric (Ecc) phase with the other arm. Needle biopsies were obtained from biceps brachii before exercise (Base), immediately postexercise from each arm (post-Con and post-Ecc), and 48 h postexercise from each arm (48 h-Con and 48 h-Ecc). Electron microscopy was used to quantify the presence of disrupted fibers in each sample. Analysis of variance revealed a greater (P < or = 0.05) proportion of disrupted fibers in post-Con, post-Ecc, 48 h-Con, and 48 h-Ecc samples compared with Base. Significantly more fibers were disrupted in post-Ecc (82%) and 48 h-Ecc (80%) samples compared with post-Con (33%) and 48 h-Con (37%), respectively. Voluntary and evoked strength measurements recovered to Base values within 24 h in the Con arm but remained depressed (P < or = 0.05) for 72-96 h in the Ecc arm. These data indicate that both the raising and lowering phases of weightlifting produced myofibrillar disruption, with the greatest disruption occurring during the lowering phase.
We have previously quantified the extent of myofibrillar disruption which occurs following an acute bout of resistance exercise in untrained men, however the response of well-trained subjects is not known. We therefore recruited six strength-trained men, who ceased training for 5 days and then performed 8 sets of 8 uni-lateral repetitions, using a load equivalent to 80% of their concentric (Con) 1-repetition maximum. One arm performed only Con actions by lifting the weight and the other arm performed only eccentric actions (Ecc) by lowering it. Needle biopsy samples were obtained from biceps brachii of each arm approximately 21 h following exercise, and at baseline (i.e., after 5 days without training), and subsequently analyzed using electron microscopy to quantify myofibrillar disruption. A greater (P < or = 0.05) proportion of disrupted fibres was found in the Ecc arm (45 +/- 11%) compared with baseline values (4 +/- 2%), whereas fibre disruption in the Con arm (27 +/- 4%) was not different (P > 0.05) from baseline values. The proportion of disrupted fibres and the magnitude of disruption (quantified by sarcomere counting) was considerably less severe than previously observed in untrained subjects after an identical exercise bout. Mixed muscle protein synthesis, assessed from approximately 21-29 h post-exercise, was not different between the Con- and Ecc-exercised arms. We conclude that the Ecc phase of resistance exercise is most disruptive to skeletal muscle and that training attenuates the severity of this effect. Moreover, it appears that fibre disruption induced by habitual weightlifting exercise is essentially repaired after 5 days of inactivity in trained men.
Lack of staining for desmin in muscles in animal models of eccentric exercise has been suggested to reflect disruption of the desmin intermediate filament network and proposed to cause disruption of the myofibrillar apparatus and deterioration of muscle fibers. In a recent study, we examined muscle biopsies from persons who had performed different eccentric exercise protocols, which induced delayed onset muscle soreness (DOMS). We were unable to verify that loss of staining for desmin was a feature of sore muscles. Nevertheless, we observed changes in the desmin cytoskeleton, but the meaning of the observations was not conclusive. In the present study, a high resolution immunocytochemical method was used to investigate the changes of desmin and actin in human muscles following a bout of eccentric exercise that lead to DOMS 2-3 days post-exercise. Biopsies were taken before exercise and 1 h and 2-3 and 7-8 days after exercise. Phalloidin, a ligand that labels filamentous actin, and anti-desmin antibodies were used to stain semithin (approximately 0.5 micro m) cryosections. At 1 h post-exercise, the staining of actin and desmin did not differ from the controls, whereas in biopsies taken 2-3 and 7-8 days after exercise, 12.5% (SD 5.8%) and 6.1% (SD 2.3%) fibers showed areas of increased staining for actin. Corresponding values for fibers with increased staining for both actin and desmin were 8.7% (SD 3.9%) and 11.4% (SD 4.6%), respectively. We suggest that the increased staining of actin and desmin reflects an increased synthesis of these proteins as part of an adaptation process following the unaccustomed eccentric exercise.
Following contraction-induced damage of skeletal muscle there is a loss of calcium homeostasis. Attenuating the damage-induced rise in myocellular calcium concentration may reduce proteolytic activation and attenuate other indices of damage; calcium channel blockers have been shown to be effective in this regard. The effect of administration of a calcium channel blocker (CCB), amlodipine, on indices of muscle damage following a unilateral 'damage protocol', during which subjects performed 300 maximal isokinetic (0.52 rad s(-1)) eccentric contractions with the knee extensors was investigated. The design was a randomized, double-blind crossover. On one occasion, prior to the damage protocol, subjects consumed CCB for 7 days prior to and for 7 days following the damage protocol. Biopsies were taken from the vastus lateralis prior to (baseline) and following the damage protocol at 4 h and 24 h post-damage. Isometric peak knee extensor torque was reduced (P < 0.05) immediately post-, 24 h post- and 48 h post-damage protocol compared to pre-exercise values with no effect of treatment. Desmin disruption was attenuated (P < 0.05) with CCB versus placebo at 4 h post-damage. Z-band streaming was significantly (P < 0.05) elevated compared to baseline at both times post-damage, but was lower with CCB at 4 h (P < 0.05). Damage resulted in increased inflammatory cell (macrophage) infiltration into skeletal muscle at both 4 h and 24 h post-damage, with no effect of CCB. Neutrophil number was elevated by the damage protocol, but was higher at 24 h post-damage in the CCB condition (P < 0.05). Creatine kinase (CK) activity was higher (P < 0.05) at 24 h and 48 h following the damage protocol compared to baseline, with no effect of treatment. In conclusion, the reduction in desmin disruption and Z-band streaming indicates that CCB attenuated, or delayed, the contraction-induced damage to sarcomeric proteins.
The purpose of the present investigation was to determine how fasted-state protein synthesis was affected, acutely, by resistance training. Eight men (24.8+/-1.7 years, body mass index=23.2+/-1.0 kg m-2; means+/-s.e.m.) undertook an 8 week programme of unilateral resistance exercise training (3 sessions week-1, progression from two to four sets; intensity was 80% of the subjects' single repetition maximum (1RM): knee extension and leg press). Following training, subjects underwent two primed constant infusions of l-[ring-13C6]phenylalanine to determine mixed and myofibrillar muscle protein synthesis (MPS) at rest and 12 h after an acute bout of resistance exercise at the same exercise intensity--each leg 80% of 1RM. Biopsies (vastus lateralis) were taken to measure incorporation of labelled phenylalanine into mixed and myofibrillar skeletal muscle proteins and yield fractional MPS. Training resulted in significant dynamic strength gains that were greater (P<0.001) in the trained leg. Hypertrophy of type IIa and IIx fibres (P<0.05) was observed following training. After training, resting mixed MPS rate was elevated (+48%; P<0.05). Acutely, resistance exercise stimulated mixed MPS only in the untrained leg (P<0.05). Myofibrillar MPS was unchanged at rest following training (P=0.61). Myofibrillar MPS increased after resistance exercise (P<0.05), but was not different between the trained and untrained legs (P=0.36). We observed divergent changes in resting mixed versus myofibrillar protein synthesis with training. In addition, resistance training modified the acute response of MPS to resistance exercise by dampening the increased synthesis of non-myofibrillar proteins while maintaining the synthesis of myofibrillar proteins.
Muscle protein synthesis (MPS) is stimulated by resistance exercise (RE) and is further stimulated by protein ingestion. The summation of periods of RE-induced increases in MPS can induce hypertrophy chronically. As such, studying the response of MPS with resistance training (RT) is informative, as adaptations in this process can modulate muscle mass gain. Previous studies have shown that the amplitude and duration of increases in MPS after an acute bout of RE are modulated by an individual's training status. Nevertheless, it has been shown that the initial responses of MPS to RE and nutrition are not correlated with subsequent hypertrophy. Thus, early acute responses of MPS in the hours after RE, in an untrained state, do not capture how MPS can affect RE-induced muscle hypertrophy. The purpose of this review is provide an in-depth understanding of the dynamic process of muscle hypertrophy throughout RT by examining all of the available data on MPS after RE and in different phases of an RT programme. Analysis of the time course and the overall response of MPS is critical to determine the potential protein accretion after an RE bout. Exercise-induced increases in MPS are shorter lived and peak earlier in the trained state than in the untrained state, resulting in a smaller overall muscle protein synthetic response in the trained state. Thus, RT induces a dampening of the MPS response, potentially limiting protein accretion, but when this occurs remains unknown.
Resistance exercise (RE) and aerobic exercise are recommended for older adults for fitness and strength. High-intensity interval exercise (HIIT) is an understudied but potent potential alternative to aerobic exercise. This study aimed to determine how each mode of exercise affected the integrated day-to-day response of muscle protein synthesis.
Sedentary men (n = 22; 67±4 years; body mass index: 27.0±2.6 kg m(-) (2) [mean ± SEM]) were randomly assigned to perform RE, aerobic exercise, or HIIT. Participants consumed a stable isotope tracer (D2O) for 9 days. Daily saliva samples were taken to measure tracer incorporation in body water. Muscle biopsies were obtained on Days 5-8 of D2O consumption to measure tracer incorporation into muscle at rest, 24 hours, and 48 hours following each exercise bout: RE (3 × 10 repetitions: leg extensor and press, 95% 10RM), HIIT (10 × 1 minute, 95% maximal heart rate [HRmax]), or aerobic exercise (30 minutes, 55%-60% HRmax).
Myofibrillar protein fractional synthetic rate was elevated, relative to rest, at 24 and 48 hours following RE and HIIT. The increase in myofibrillar fractional synthetic rate was greater following RE versus HIIT at both time points. HIIT was the only mode of exercise to increase sarcoplasmic protein fractional synthetic rate 24-hour postexercise (2.30±0.34% d(-) (1) vs 1.83±0.21% d(-) (1)).
This study shows that in older men, changes in muscle protein synthesis in response to certain exercises are long lasting and that HIIT significantly increases myofibrillar and sarcoplasmic fractional synthetic rate in this population.
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Conventionally, myofibrillar protein synthesis is measured over time periods of hours. In clinical studies, interventions occur over weeks. Functional measures over such periods may be more representative. We aimed to develop a novel method to determine myofibrillar protein fractional synthetic rate (FSR) to estimate habitual rates, while avoiding intravenous tracer infusions.
Four healthy males were given 100 g water enriched to 70 Atom % with (2) H2 O as a single oral bolus. Vastus-lateralis needle biopsies were performed and plasma samples collected, 3-13 days post-dose. (2) H enrichment in body water was measured in plasma using continuous flow isotope ratio mass spectrometry (IRMS). Myofibrillar protein was isolated from muscle biopsies and acid hydrolysed. (2) H enrichment of protein-bound and plasma-free alanine was measured by gas chromatography (GC)/pyrolysis/IRMS. Myofibrillar protein FSR was calculated (% day(-1) ).
The tracer bolus raised the initial enrichment of body water to 1514 ppm (2) H excess. Water elimination followed a simple exponential. The average elimination half-time was 8.3 days. Plasma alanine, labelled during de novo synthesis, followed the same elimination kinetics as water. The weighted average myofibrillar protein FSR from the four subjects was 1.38 % day(-1) (range, 1.0-1.9 % day(-1) ).
Myofibrillar protein FSR was measured in free-living healthy individuals over 3-13 days. Using a single oral (2) H2 O bolus, endogenous labelling of alanine occurred in a predictable manner giving estimates of synthesis comparable with published values. Furthermore, the protocol does not compromise the ability to measure other important metabolic processes such as total energy expenditure. Copyright © 2013 John Wiley & Sons, Ltd.
Objectives:
To compare the susceptibility of elbow flexors (EF) and knee extensors (KE) to eccentric exercise-induced muscle damage in older individuals, since ageing could modulate the difference in the susceptibility to muscle damage between muscles.
Design:
Cross-sectional and cross-over study design.
Methods:
Eight older (61.6 ± 1.8 years) adults performed 5 sets of 6 maximal isokinetic (90° s(-1)) eccentric contractions of the EF (range of motion: 80-20°) and KE (30-90°) with the non-dominant limb in a randomised, counterbalanced order with 2 weeks between bouts. Maximal voluntary isometric (MVC-ISO) and concentric contraction torque, optimum angle, range of motion (ROM), muscle soreness and serum creatine kinase (CK) activity were measured before, immediately after (except CK), and 24, 48, 72 and 96 h following exercise. Normalised changes in the variables following exercise were compared between EF and KE by a mixed model analysis of variance.
Results:
Only MVC-ISO and ROM demonstrated significant group effects (p<0.05) for the comparison between EF and KE. Additionally, no significant group vs. time interactions (p>0.05) were found between EF and KE for any of the dependent variables changes.
Conclusions:
These results suggest that the KE of older adults are relatively as susceptible to muscle damage as their EF, or at the very least, the difference between EF and KE are small for older adults.
Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations.
Objective: The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations.
Design: A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training.
Results: Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects.
Conclusion: Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects.
We have reported that the acute postexercise increases in muscle protein synthesis rates, with differing nutritional support, are predictive of longer-term training-induced muscle hypertrophy. Here, we aimed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis. Eighteen men (21 ± 1 yr, 22.6 ± 2.1 kg/m(2); means ± SE) had their legs randomly assigned to two of three training conditions that differed in contraction intensity [% of maximal strength (1 repetition maximum)] or contraction volume (1 or 3 sets of repetitions): 30%-3, 80%-1, and 80%-3. Subjects trained each leg with their assigned regime for a period of 10 wk, 3 times/wk. We made pre- and posttraining measures of strength, muscle volume by magnetic resonance (MR) scans, as well as pre- and posttraining biopsies of the vastus lateralis, and a single postexercise (1 h) biopsy following the first bout of exercise, to measure signaling proteins. Training-induced increases in MR-measured muscle volume were significant (P < 0.01), with no difference between groups: 30%-3 = 6.8 ± 1.8%, 80%-1 = 3.2 ± 0.8%, and 80%-3= 7.2 ± 1.9%, P = 0.18. Isotonic maximal strength gains were not different between 80%-1 and 80%-3, but were greater than 30%-3 (P = 0.04), whereas training-induced isometric strength gains were significant but not different between conditions (P = 0.92). Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation (P < 0.05) of p70S6K only in the 80%-1 and 80%-3 conditions. There was no correlation between phosphorylation of any signaling protein and hypertrophy. In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure resulted in similar hypertrophy as a heavy load lifted to failure.
We aimed to determine if the time that muscle is under loaded tension during low intensity resistance exercise affects the synthesis of specific muscle protein fractions or phosphorylation of anabolic signalling proteins. Eight men (24 ± 1 years (sem), BMI = 26.5 ± 1.0 kg m(-2)) performed three sets of unilateral knee extension exercise at 30% of one-repetition maximum strength involving concentric and eccentric actions that were 6 s in duration to failure (SLOW) or a work-matched bout that consisted of concentric and eccentric actions that were 1 s in duration (CTL). Participants ingested 20 g of whey protein immediately after exercise and again at 24 h recovery. Needle biopsies (vastus lateralis) were obtained while fasted at rest and after 6, 24 and 30 h post-exercise in the fed-state following a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine. Myofibrillar protein synthetic rate was higher in the SLOW condition versus CTL after 24-30 h recovery (P < 0.001) and correlated to p70S6K phosphorylation (r = 0.42, P = 0.02). Exercise-induced rates of mitochondrial and sarcoplasmic protein synthesis were elevated by 114% and 77%, respectively, above rest at 0-6 h post-exercise only in the SLOW condition (both P < 0.05). Mitochondrial protein synthesis rates were elevated above rest during 24-30 h recovery in the SLOW (175%) and CTL (126%) conditions (both P < 0.05). Lastly, muscle PGC-1α expression was increased at 6 h post-exercise compared to rest with no difference between conditions (main effect for time, P < 0.001). These data show that greater muscle time under tension increased the acute amplitude of mitochondrial and sarcoplasmic protein synthesis and also resulted in a robust, but delayed stimulation of myofibrillar protein synthesis 24-30 h after resistance exercise.
The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.
Junctophilins (JP1 and JP2) are expressed in skeletal muscle and are the primary proteins involved in transverse (T)-tubule and sarcoplasmic reticulum (SR) membrane apposition. During the performance of eccentric contractions, the apposition of T-tubule and SR membranes may be disrupted, resulting in excitation-contraction (EC) coupling failure and thus reduced force-producing capacity. In this study, we made three primary observations: 1) through the first 3 days after the performance of 50 eccentric contractions in vivo by the left hindlimb anterior crural muscles of female mice, both JP1 and JP2 were significantly reduced by approximately 50% and 35%, respectively, while no reductions were observed after the performance of nonfatiguing concentric contractions; 2) following the performance of a repeated bout of 50 eccentric contractions in vivo, only JP1 was immediately reduced ( approximately 30%) but recovered by 3-day postinjury in tandem with the recovery of strength and EC coupling; and 3) following the performance of 10 eccentric contractions at either 15 degrees or 35 degrees C by isolated mouse extensor digitorum longus (EDL) muscle, isometric force, EC coupling, and JP1 and JP2 were only reduced after the eccentric contractions performed at 35 degrees C. Regression analysis of JP1 and JP2 content in tibialis anterior and EDL muscles from each set of experiments indicated that JP damage is significantly associated with early (0-3 days) strength deficits after performance of eccentric contractions (R = 0.49; P < 0.001). As a whole, the results of this study indicate that JP damage plays a role in early force deficits due to EC coupling failure following the performance of eccentric contractions.
The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 yr, body mass index = 23.1 +/- 0.6 kg/m(2)) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men.
We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 +/- 1.1 years, BMI = 26 +/- 3.5 kg m(-2)) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF-1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 +/- 0.007, LH = 0.071 +/- 0.008, HH = 0.064 +/- 0.014% h(-1); P < 0.05) with no effect of elevated hormones (P = 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post-exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS.
We aimed to determine whether there is a differential stimulation of the contractile myofibrillar and the cellular sarcoplasmic proteins after ingestion of protein and how this is affected by resistance exercise. Fasted (FAST) muscle protein synthesis was measured in seven healthy young men with a primed constant infusion of L-[ring-(13)C(6)]phenylalanine. Participants then performed an intense bout of unilateral resistance exercise followed by the consumption of 25 g of whey protein to maximally stimulate protein synthesis. In the rested (FED) leg myofibrillar (MYO) protein synthesis was elevated (P < 0.01) above FAST at 3 h (approximately 163%) but not at 1 and 5 h (P > 0.05). In contrast, MYO protein synthesis in the exercised (FED-EX) leg was stimulated above FAST at 1, 3 and 5 h (approximately 100, 216, and 229%, respectively; P < 0.01) with the increase at 5 h being greater than FED (P < 0.01). Thus, the synthesis of muscle contractile proteins is stimulated by both feeding and resistance exercise early (1 h) but has a greater duration and amplitude after resistance exercise. Sarcoplasmic (SARC) protein synthesis was similarly elevated (P < 0.01) above FAST by approximately 104% at 3 h in both FED and FED-EX suggesting SARC protein synthesis is stimulated by feeding but that this response is not augmented by resistance exercise. In conclusion, myofibrillar and sarcoplasmic protein synthesis are similarly, but transiently, stimulated with protein feeding. In contrast, resistance exercise rapidly stimulates and sustains the synthesis of only the myofibrillar protein fraction after protein ingestion. These data highlight the importance of measuring the synthetic response of specific muscle protein fractions when examining the effects of exercise and nutrition.
The anabolic effect of resistance exercise is enhanced by the provision of dietary protein.
We aimed to determine the ingested protein dose response of muscle (MPS) and albumin protein synthesis (APS) after resistance exercise. In addition, we measured the phosphorylation of candidate signaling proteins thought to regulate acute changes in MPS.
Six healthy young men reported to the laboratory on 5 separate occasions to perform an intense bout of leg-based resistance exercise. After exercise, participants consumed, in a randomized order, drinks containing 0, 5, 10, 20, or 40 g whole egg protein. Protein synthesis and whole-body leucine oxidation were measured over 4 h after exercise by a primed constant infusion of [1-(13)C]leucine.
MPS displayed a dose response to dietary protein ingestion and was maximally stimulated at 20 g. The phosphorylation of ribosomal protein S6 kinase (Thr(389)), ribosomal protein S6 (Ser(240/244)), and the epsilon-subunit of eukaryotic initiation factor 2B (Ser(539)) were unaffected by protein ingestion. APS increased in a dose-dependent manner and also reached a plateau at 20 g ingested protein. Leucine oxidation was significantly increased after 20 and 40 g protein were ingested.
Ingestion of 20 g intact protein is sufficient to maximally stimulate MPS and APS after resistance exercise. Phosphorylation of candidate signaling proteins was not enhanced with any dose of protein ingested, which suggested that the stimulation of MPS after resistance exercise may be related to amino acid availability. Finally, dietary protein consumed after exercise in excess of the rate at which it can be incorporated into tissue protein stimulates irreversible oxidation.
Muscle regeneration following injury is dependent on the ability of muscle satellite cells to activate, proliferate and fuse with damaged fibres. This process is controlled by the myogenic regulatory factors (MRF). Little is known about the temporal relation of the MRF with the expression of known myogenic growth factors (i.e. IGF-1) in humans following muscle damage. Eight subjects (20.6 +/- 2.1 years; 81.4 +/- 9.8 kg) performed 300 lengthening contractions (180 deg s(-1)) of their knee extensors in one leg on a dynamometer. Blood and muscle samples were collected before and at 4 (T4), 24 (T24), 72 (T72) and 120 h (T120) post-exercise. Mechano growth factor (MGF), IGF-1Ea and IGF-1Eb mRNA were quantified. Serum IGF-1 did not change over the post-exercise time course. IGF-1Ea and IGF-1Eb mRNA increased approximately 4- to 6-fold by T72 (P < 0.01) and MGF mRNA expression peaked at T24 (P = 0.005). MyoD mRNA expression increased approximately 2-fold at T4 (P < 0.05). Myf5 expression peaked at T24 (P < 0.05), while MRF4 and myogenin mRNA expression peaked at T72 (P < 0.05). Myf5 expression strongly correlated with the increase in MGF mRNA (r(2) = 0.83; P = 0.03), while MRF4 was correlated with both IGF-1Ea and -Eb (r(2) = 0.90; r(2) = 0.81, respectively; P < 0.05). Immunofluorescence analysis showed IGF-1 protein expression localized to satellite cells at T24, and to satellite cells and the myofibre at T72 and T120; IGF-1 was not detected at T0 or T4. These results suggest that the temporal response of MGF is probably related to the activation/proliferation phase of the myogenic programme as marked by an increase in both Myf5 and MyoD, while IGF-1Ea and -Eb may be temporally related to differentiation as marked by an increase in MRF4 and myogenin expression following acute muscle damage.
This brief review focuses on the time course of changes in muscle function and other correlates of muscle damage following maximal effort eccentric actions of the forearm flexor muscles. Data on 109 subjects are presented to describe an accurate time course of these changes and attempt to establish relationships among the measures. Peak soreness is experienced 2-3 d postexercise while peak swelling occurs 5 d postexercise. Maximal strength and the ability to fully flex the arm show the greatest decrements immediately after exercise with a linear restoration of these functions over the next 10 d. Blood creatine kinase (CK) levels increase precipitously at 2 d after exercise which is also the time when spontaneous muscle shortening is most pronounced. Whether the similarity in the time courses of some of these responses implies that they are caused by similar factors remains to be determined. Performance of one bout of eccentric exercise produces an adaptation such that the muscle is more resistant to damage from a subsequent bout of exercise. The length of the adaptation differs among the measures such that when the exercise regimens are separated by 6 wk, all measures show a reduction in response on the second, compared with the first, bout. After 10 wk, only CK and muscle shortening show a reduction in response. After 6 months only the CK response is reduced. A combination of cellular factors and neurological factors may be involved in the adaptation process.
Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown rate (FBR) were examined after an isolated bout of either concentric or eccentric resistance exercise. Subjects were eight untrained volunteers (4 males, 4 females). Mixed muscle protein FSR and FBR were determined using primed constant infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively. Subjects were studied in the fasted state on four occasions: at rest and 3, 24, and 48 h after a resistance exercise bout. Exercise was eight sets of eight concentric or eccentric repetitions at 80% of each subject's concentric 1 repetition maximum. There was no significant difference between contraction types for either FSR, FBR, or net balance (FSR minus FBR). Exercise resulted in significant increases above rest in muscle FSR at all times: 3 h = 112%, 24 h = 65%, 48 h = 34% (P < 0.01). Muscle FBR was also increased by exercise at 3 h (31%; P < 0.05) and 24 h (18%; P < 0.05) postexercise but returned to resting levels by 48 h. Muscle net balance was significantly increased after exercise at all time points [(in %/h) rest = -0.0573 +/- 0.003 (SE), 3 h = -0.0298 +/- 0.003, 24 h = -0.0413 +/- 0.004, and 48 h = -0.0440 +/- 0.005], and was significantly different from zero at all time points (P < 0.05). There was also a significant correlation between FSR and FBR (r = 0.88, P < 0.001). We conclude that exercise resulted in an increase in muscle net protein balance that persisted for up to 48 h after the exercise bout and was unrelated to the type of muscle contraction performed.
We examined the effect of resistance training on the response of mixed muscle protein fractional synthesis (FSR) and breakdown rates (FBR) by use of primed constant infusions of [2H5]phenylalanine and [15N]phenylalanine, respectively, to an isolated bout of pleiometric resistance exercise. Trained subjects, who were performing regular resistance exercise (trained, T; n = 6), were compared with sedentary, untrained controls (untrained, UT; n = 6). The exercise test consisted of 10 sets (8 repetitions per set) of single-leg knee flexion (i.e., pleiometric muscle contraction during lowering) at 120% of the subjects' predetermined single-leg 1 repetition maximum. Subjects exercised one leg while their contralateral leg acted as a nonexercised (resting) control. Exercise resulted in an increase, above resting, in mixed muscle FSR in both groups (UT: rest, 0.036 +/- 0.002; exercise, 0.0802 +/- 0.01; T: rest, 0.045 +/- 0.004; exercise, 0.067 +/- 0.01; all values in %/h; P < 0.01). In addition, exercise resulted in an increase in mixed muscle FBR of 37 +/- 5% (rest, 0.076 +/- 0.005; exercise, 0.105 +/- 0.01; all values in %/h; P < 0.01) in the UT group but did not significantly affect FBR in the T group. The resulting muscle net balance (FSR - FBR) was negative throughout the protocol (P < 0.05) but was increased in the exercised leg in both groups (P < 0.05). We conclude that pleiometric muscle contractions induce an increase in mixed muscle protein synthetic rate within 4 h of completion of an exercise bout but that resistance training attenuates this increase. A single bout of pleiometric muscle contractions also increased the FBR of mixed muscle protein in UT but not in T subjects.
We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion of L-[ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased approximately 150-640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (-50 +/- 23 nmol. min-1. 100 ml leg volume-1) to positive during MAA ingestion (17 +/- 13 nmol. min-1. 100 ml leg volume-1) and EAA (29 +/- 14 nmol. min-1. 100 ml leg volume-1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused.
It is generally accepted that the primary mechanisms governing skeletal muscle hypertrophy are satellite cell activation, proliferation, and differentiation. Specific growth factors and hormones modulate satellite cell activity during normal muscle growth, but as a consequence of resistance exercise additional regulators may stimulate satellite cells to contribute to gains in myofiber size and number. Present knowledge of the regulation of the cellular, biochemical and molecular events accompanying skeletal muscle hypertrophy after resistance exercise is incomplete. We propose that resistance exercise may induce satellite cells to become responsive to cytokines from the immune system and to circulating hormones and growth factors. The purpose of this paper is to review the role of satellite cells and growth factors in skeletal muscle hypertrophy that follows resistance exercise.
Eccentrically biased exercise results in skeletal muscle damage and stimulates adaptations in muscle, whereby indexes of damage are attenuated when the exercise is repeated. We hypothesized that changes in ultrastructural damage, inflammatory cell infiltration, and markers of proteolysis in skeletal muscle would come about as a result of repeated eccentric exercise and that gender may affect this adaptive response. Untrained male (n = 8) and female (n = 8) subjects performed two bouts (bout 1 and bout 2), separated by 5.5 wk, of 36 repetitions of unilateral, eccentric leg press and 100 repetitions of unilateral, eccentric knee extension exercises (at 120% of their concentric single repetition maximum), the subjects' contralateral nonexercised leg served as a control (rest). Biopsies were taken from the vastus lateralis from each leg 24 h postexercise. After bout 2, the postexercise force deficit and the rise in serum creatine kinase (CK) activity were attenuated. Women had lower serum CK activity compared with men at all times (P < 0.05), but there were no gender differences in the relative magnitude of the force deficit. Muscle Z-disk streaming, quantified by using light microscopy, was elevated vs. rest only after bout 1 (P < 0.05), with no gender difference. Muscle neutrophil counts were significantly greater in women 24 h after bout 2 vs. rest and bout 1 (P < 0.05) but were unchanged in men. Muscle macrophages were elevated in men and women after bout 1 and bout 2 (P < 0.05). Muscle protein content of the regulatory calpain subunit remained unchanged whereas ubiquitin-conjugated protein content was increased after both bouts (P < 0.05), with a greater increase after bout 2. We conclude that adaptations to eccentric exercise are associated with attenuated serum CK activity and, potentially, an increase in the activity of the ubiquitin proteosome proteolytic pathway.
Vitamin E supplementation may confer a protective effect against eccentrically biased exercise-induced muscle damage through stabilization of the cell membrane and possibly via inhibition of free radical formation. Evidence supporting a protective role of vitamin E after contraction-induced muscle injury in humans is, however, inconsistent. The present study sought to determine the effect of vitamin E supplementation on indices of exercise-induced muscle damage and the postexercise inflammatory response after performance of repeated eccentric muscle contractions.
Young healthy men performed a bout of 240 maximal isokinetic eccentric muscle contractions (0.52 rad.s-1) after being supplemented for 30 d with either vitamin E (N = 9; 1200 IU.d-1) or placebo (N = 7; safflower oil).
Measurements of torque (isometric and concentric) decreased (P < 0.05) below preexercise values immediately post- and at 48 h post-exercise. Biopsies taken 24 h postexercise showed a significant increase in the amount of extensive Z-band disruption (P < 0.01); however, neither the torque deficit nor the extent of Z-band disruption were affected by vitamin E. Exercise resulted in increased macrophage cell infiltration (P = 0.05) into muscle, which was also unaffected by vitamin E. Serum CK also increased as a result of the exercise (P < 0.05) with no effect of vitamin E.
We conclude that vitamin E supplementation (30 d at 1200 IU.d-1), which resulted in a 2.8-fold higher serum vitamin E concentration (P < 0.01), had no affect on indices of contraction-induced muscle damage nor inflammation (macrophage infiltration) as a result of eccentrically biased muscle contractions.
Exercise-induced muscle injury in humans frequently occurs after unaccustomed exercise, particularly if the exercise involves a large amount of eccentric (muscle lengthening) contractions. Direct measures of exercise-induced muscle damage include cellular and subcellular disturbances, particularly Z-line streaming. Several indirectly assessed markers of muscle damage after exercise include increases in T2 signal intensity via magnetic resonance imaging techniques, prolonged decreases in force production measured during both voluntary and electrically stimulated contractions (particularly at low stimulation frequencies), increases in inflammatory markers both within the injured muscle and in the blood, increased appearance of muscle proteins in the blood, and muscular soreness. Although the exact mechanisms to explain these changes have not been delineated, the initial injury is ascribed to mechanical disruption of the fiber, and subsequent damage is linked to inflammatory processes and to changes in excitation-contraction coupling within the muscle. Performance of one bout of eccentric exercise induces an adaptation such that the muscle is less vulnerable to a subsequent bout of eccentric exercise. Although several theories have been proposed to explain this "repeated bout effect," including altered motor unit recruitment, an increase in sarcomeres in series, a blunted inflammatory response, and a reduction in stress-susceptible fibers, there is no general agreement as to its cause. In addition, there is controversy concerning the presence of sex differences in the response of muscle to damage-inducing exercise. In contrast to the animal literature, which clearly shows that females experience less damage than males, research using human studies suggests that there is either no difference between men and women or that women are more prone to exercise-induced muscle damage than are men.
Resistance training changes the balance of muscle protein turnover, leading to gains in muscle mass. A longitudinal design was employed to assess the effect that resistance training had on muscle protein turnover in the fed state. A secondary goal was investigation of the potential interactive effects of creatine (Cr) monohydrate supplementation on resistance-training-induced adaptations. Young (N = 19, 23.7 +/- 3.2 year), untrained (UT), healthy male subjects completed an 8-week resistance-training program (6 d/week). Supplementation with Cr had no impact on any of the variables studied; hence, all subsequent data were pooled. In the UT and trained (T) state, subjects performed an acute bout of resistance exercise with a single leg (exercised, EX), while their contralateral leg acted as a nonexercised (NE) control. Following exercise, subjects were fed while receiving a primed constant infusion of [d5]- and [15N]-phenylalanine to determine the fractional synthetic and breakdown rates (FSR and FBR), respectively, of skeletal muscle proteins. Acute exercise increased FSR (UT-NE, 0.065 +/- 0.025 %/h; UT-EX, 0.088 +/- 0.032 %/h; P < 0.01) and FBR (UT-NE, 0.047 +/- 0.023 %/h; UT-EX, 0.058 +/- 0.026 %/h; P < 0.05). Net balance (BAL = FSR - FBR) was positive in both legs (P < 0.05) but was significantly greater (+65%) in the EX versus the NE leg (P < 0.05). Muscle protein FSR and FBR were greater at rest following T (FSR for T-NE vs. UT-NE, +46%, P < 0.01; FBR for T-NE vs. UT-NE, +81%, P < 0.05). Resistance training attenuated the acute exercise-induced rise in FSR (T-NE vs. T-EX, +20%, P = 0.65). The present results demonstrate that resistance training resulted in an elevated resting muscle protein turnover but an attenuation of the acute response of muscle protein turnover to a single bout of resistance exercise.
No studies to date have reported activation of satellite cells in vivo in human muscle after a single bout of high intensity exercise. In this investigation, eight individuals performed a single bout of high intensity exercise with one leg, the contralateral leg being the control. A significant increase in mononuclear cells staining for the neural cell adhesion molecule (N-CAM) and fetal antigen 1 (FA1) were observed within the exercised human vastus lateralis muscle on days 4 and 8 post exercise. In addition, a significant increase in the concentration of the FA1 protein was determined in intramuscular dialysate samples taken from the vastus lateralis muscle of the exercising leg (day 0: 1.89 +/- 0.82 ng ml(-1); day 2: 1.68 +/- 0.37 ng ml(-1); day 4: 3.26 +/- 1.29 ng ml(-1), P < 0.05 versus basal; day 8: 4.68 +/- 2.06 ng ml(-1), P < 0.05 versus basal and control). No change was noted in the control leg. Despite this increase in N-CAM- and FA1-positive mononuclear cells, an increased expression of myogenin and the neonatal isoform of the myosin heavy chain (MHCn) was not observed. Interestingly, myofibre lesions resulting from extensive damage to the proteins within the myofibre, particularly desmin or dystrophin, were not observed, and hence did not appear to induce the expression of either N-CAM or FA1. We therefore propose that satellite cells can be induced to re-enter the cell growth cycle after a single bout of unaccustomed high intensity exercise. However, a single bout of exercise is not sufficient for the satellite cell to undergo terminal differentiation.
We aimed to determine whether there were differences in the extent and time course of skeletal muscle myofibrillar protein synthesis (MPS) and muscle collagen protein synthesis (CPS) in human skeletal muscle in an 8.5-h period after bouts of maximal muscle shortening (SC; average peak torque = 225 +/- 7 N.m, means +/- SE) or lengthening contractions (LC; average peak torque = 299 +/- 18 N.m) with equivalent work performed in each mode. Eight healthy young men (21.9 +/- 0.6 yr, body mass index 24.9 +/- 1.3 kg/m2) performed 6 sets of 10 maximal unilateral LC of the knee extensors on an isokinetic dynamometer. With the contralateral leg, they then performed 6 sets of maximal unilateral SC with work matched to the total work performed during LC (10.9 +/- 0.7 vs. 10.9 +/- 0.8 kJ, P = 0.83). After exercise, the participants consumed small intermittent meals to provide 0.1 g.kg(-1).h(-1) of protein and carbohydrate. Prior exercise elevated MPS above rest in both conditions, but there was a more rapid rise after LC (P < 0.01). The increases (P < 0.001) in CPS above rest were identical for both SC and LC and likely represent a remodeling of the myofibrillar basement membrane. Therefore, a more rapid rise in MPS after maximal LC could translate into greater protein accretion and muscle hypertrophy during chronic resistance training utilizing maximal LC.
We performed two studies to determine the effect of a resistive training program comprised of fast vs. slow isokinetic lengthening contractions on muscle fiber hypertrophy. In study I, we investigated the effect of fast (3.66 rad/s; Fast) or slow (0.35 rad/s; Slow) isokinetic high-resistance muscle lengthening contractions on muscle fiber and whole muscle cross-sectional area (CSA) of the elbow flexors was investigated in young men. Twelve subjects (23.8 +/- 2.4 yr; means +/- SD) performed maximal resistive lengthening isokinetic exercise with both arms for 8 wk (3 days/wk), during which they trained one arm at a Fast velocity while the contralateral arm performed an equivalent number of contractions at a Slow velocity. Before (Pre) and after (Post) the training, percutaneous muscle biopsies were taken from the midbelly of the biceps brachii and analyzed for fiber type and CSA. Type I muscle fiber size increased Pre to Post (P < 0.05) in both Fast and Slow arms. Type IIa and IIx muscle fiber CSA increased in both arms, but the increases were greater in the Fast- vs. the Slow-trained arm (P < 0.05). Elbow flexor CSA increased in Fast and Slow arms, with the increase in the Fast arm showing a trend toward being greater (P = 0.06). Maximum torque-generating capacity also increased to a greater degree (P < 0.05) in the Fast arm, regardless of testing velocity. In study II, we attempted to provide some explanation of the greater hypertrophy observed in study I by examining an indicator of protein remodeling (Z-line streaming), which we hypothesized would be greater in the Fast condition. Nine men (21.7 +/- 2.4 yr) performed an acute bout (n = 30, 3 sets x 10 repetitions/set) of maximal lengthening contractions at Fast and Slow velocities used in the training study. Biopsies revealed that Fast lengthening contractions resulted in more (185 +/- 1 7%; P < 0.01) Z-band streaming per millimeter squared muscle vs. the Slow arm. In conclusion, training using Fast (3.66 rad/s) lengthening contractions leads to greater hypertrophy and strength gains than Slow (0.35 rad/s) lengthening contractions. The greater hypertrophy seen in the Fast-trained arm (study I) may be related to a greater amount of protein remodeling (Z-band streaming; study II).