Article

Survival of the fittest: VO2max, a key predictor of longevity?

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Abstract

Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), is related to functional capacity and human performance and has been shown to be a strong and independent predictor of all-cause and disease-specific mortality. The purpose of this review is to emphasize age-related physiological adaptations occurring with regular exercise training, with specific reference to the main organs (lung, heart, skeletal muscles) involved in oxygen delivery and utilization as well as the importance of exercise training for promoting life expectancy in clinically referred populations. As yet, it is not possible to extend the genetically fixed lifespan with regular exercise training, but to give the years more life. This is where physical fitness plays an important role

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... [8,9] Cardiorespiratory fitness is arguably the strongest predictor of all-cause mortality secondary to age, with plenty of evidence emphasising its analytical and clinical validity. [10,11,12] The physiological factors that were most often associated with maximum oxygen consumption (VO2max) include stroke volume (SV), cardiac output (CO), maximum heart rate (HRmax), central adiposity and muscular strength. [13] Thus, we believe VO2max could be an appropriate marker of an individual's physical health when testing for functions that perhaps interfere with physical activity. ...
... Besides, cardiac growth and reduced total peripheral resistance led to improved cardiac compliance, potentially enhancing stroke volume. [10,49,50] Few ageing studies revealed over 15% reduction in maximum SV accounted for a 30% lower VO2max in master athletes, reinforcing the relationship. [51] Moreover, CO was reported proportional to VO2 in master athletes [52] , Wagner [53] highlighted the majority of variance in absolute VO2max was attributed to the decline of CO due to the fall in VO2max with ageing being related to a reduced blood flow. ...
... The buildup of norepinephrine enhanced the inotropic effect and caused the contractility of the heart to increase. [10,57] These mechanisms likely result in the association between HRmax and VO2max. ...
Experiment Findings
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This is the first study to examine the relationship between maximal oxygen consumption (VO2max) and a wide range of physiological variables covering central mechanisms, body fat and muscle. Given that using age information to group participants in research is somewhat oversimplistic, with ages typically grouped into arbitrary ranges, it is questioned whether this reflects the stages of ageing and level of body functions. Here, we investigate whether VO2max is a good predictor of physiological functions and, therefore the possibility of grouping participants based on VO2max. Each participant performed a cardiopulmonary exercise test on a cycle ergometer, knee extensor strength test on a custom-built dynamometer and grip strength tested with a handgrip dynamometer. Significant correlations were observed with indices including resting systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), maximal heart rate (HRmax), body percentage of fat and high-density lipoprotein (HDL). Interestingly, no association was found with resting stroke volume (SV) and cardiac output (CO). Even if HRmax showed the closest relationship with VO2max (r = 0.349, P = 0.025), most of the indexes showed only slight or no association with VO2max, precluding the recognition of physiological functions of any individuals. Hence, our hypothesis was rejected, suggesting VO2max is not a suitable hallmark for grouping participants in studies.
... Aged-related decreases in aerobic capacity are smaller in highly trained individuals (~0.5% per annum) than those who are moderately trained or sedentary (~1.0% per annum) (Tanaka, 2017;Trappe, 2007). Despite the similar relative decreases in aerobic capacity in trained and sedentary ageing populations, the absolute values of those who are trained remain higher than those who are sedentary (Strasser & Burtscher, 2018;Valenzuela et al., 2020), thus enhancing successful ageing in physically active older individuals. Indeed, research has shown that aerobic capacity has a positive relationship with endurance exercise performance (Midgley et al., 2007), and is related to positive health outcomes and enhanced longevity in older individuals (Strasser & Burtscher, 2018;Valenzuela et al., 2020). ...
... Despite the similar relative decreases in aerobic capacity in trained and sedentary ageing populations, the absolute values of those who are trained remain higher than those who are sedentary (Strasser & Burtscher, 2018;Valenzuela et al., 2020), thus enhancing successful ageing in physically active older individuals. Indeed, research has shown that aerobic capacity has a positive relationship with endurance exercise performance (Midgley et al., 2007), and is related to positive health outcomes and enhanced longevity in older individuals (Strasser & Burtscher, 2018;Valenzuela et al., 2020). For example, every increase of 1 ml.kg.min -1 of VO 2max has been shown to be associated with a 9% reduction in relative risk of all-cause mortality (Laukkanen et al., 2016). ...
... Cardiorespiratory fitness (CRF) is an intrinsic physiological trait that is also associated with longevity [13]. CRF, defined as the ability of the circulatory and respiratory systems to supply oxygen to skeletal muscles during sustained exercise, is routinely measured by maximal oxygen uptake (VO 2 max) during a graded exercise test. ...
... CRF, defined as the ability of the circulatory and respiratory systems to supply oxygen to skeletal muscles during sustained exercise, is routinely measured by maximal oxygen uptake (VO 2 max) during a graded exercise test. CRF is a highly heritable trait in humans [10] and, importantly, inherited high CRF phenotypes mirror the CR-induced phenotypes, including lower adiposity [11], higher cardiometabolic health [12], and greater longevity [13]. As such, a key question in the field is whether CR "phenocopies" the intrinsic high-CRF characteristics via similar, overlapping, or distinct mechanisms. 1 We have been characterizing an established rat model selectively bred from a genetically heterogeneous stock (N:NIH) to generate a high capacity runner (HCR) line and low capacity runner (LCR) line in a manner that maintains genetic heterogeneity [14e16]. ...
Article
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Objective Caloric restriction (CR) is one extrinsic intervention that can improve metabolic health, and it shares many phenotypical parallels with intrinsic high cardiorespiratory fitness (CRF), including reduced adiposity, increased cardiometabolic health, and increased longevity. CRF is a highly heritable trait in humans and has been established in a genetic rat model selectively bred for high (HCR) and low (LCR) CRF, in which the HCR live longer and have reduced body weight compared to LCR. This study addresses whether the inherited high CRF phenotype occurs through similar mechanisms by which CR promotes health and longevity. Methods We compared HCR and LCR male rats fed ad libitum (AL) or calorically restricted (CR) for multiple physiological, metabolic, and molecular traits, including running capacity at 2, 8, and 12 months; per-hour metabolic cage activity over daily cycles at 6 and 12 months; and plasma lipidomics, liver and muscle transcriptomics, and body composition after 12 months of treatment. Results LCR-CR developed a physiological profile that mirrors the high-CRF phenotype in HCR-AL, including reduced adiposity and increased insulin sensitivity. HCR show higher spontaneous activity than LCR. Temporal modeling of hourly energy expenditure (EE) dynamics during the day, adjusted for body weight and hourly activity levels, suggest that CR has an EE-suppressing effect, and high-CRF has an EE-enhancing effect. Pathway analysis of gene transcripts indicates that HCR and LCR both show a response to CR that is similar in the muscle and different in the liver. Conclusions CR provides LCR a health-associated positive effect on physiological parameters that strongly resemble HCR. Analysis of whole-body EE and transcriptomics suggests that HCR and LCR show line-dependent responses to CR that may be accreditable to difference in genetic makeup. The results do not preclude the possibility that CRF and CR pathways may converge.
... The VO 2max is widely regarded as the gold standard measure of cardiorespiratory fitness and is typically determined using a cardiopulmonary exercise test (CPET) in clinical, applied physiology, and sport and exercise science settings [1,[3][4][5][6]. The VO 2max is often used to diagnose cardiovascular disease [7], predict all-cause mortality [8][9][10], develop exercise prescriptions [3,11,12], and evaluate the efficacy of exercise programmes [13][14][15]. Consequently, the validity of VO 2max values obtained during CPETs has widespread importance in clinical, sporting, and research-related contexts. ...
... The total number of participants recruited across all included studies was 1,680 (1,077 men, 473 women, and the sex of 130 participants was not specified). Included studies had a median (interquartile range [IQR]) sample size of 13 [10] participants. Participants were aged between 19 and 68 yr, all apparently healthy, and with a physical activity status ranging from sedentary to highly-trained endurance athletes. ...
Article
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Background The ‘verification phase’ has emerged as a supplementary procedure to traditional maximal oxygen uptake (VO 2max ) criteria to confirm that the highest possible VO 2 has been attained during a cardiopulmonary exercise test (CPET). Objective To compare the highest VO 2 responses observed in different verification phase procedures with their preceding CPET for confirmation that VO 2max was likely attained. Methods MEDLINE (accessed through PubMed), Web of Science, SPORTDiscus, and Cochrane (accessed through Wiley) were searched for relevant studies that involved apparently healthy adults, VO 2max determination by indirect calorimetry, and a CPET on a cycle ergometer or treadmill that incorporated an appended verification phase. RevMan 5.3 software was used to analyze the pooled effect of the CPET and verification phase on the highest mean VO 2 . Meta-analysis effect size calculations incorporated random-effects assumptions due to the diversity of experimental protocols employed. I ² was calculated to determine the heterogeneity of VO 2 responses, and a funnel plot was used to check the risk of bias, within the mean VO 2 responses from the primary studies. Subgroup analyses were used to test the moderator effects of sex, cardiorespiratory fitness, exercise modality, CPET protocol, and verification phase protocol. Results Eighty studies were included in the systematic review (total sample of 1,680 participants; 473 women; age 19–68 yr.; VO 2max 3.3 ± 1.4 L/min or 46.9 ± 12.1 mL·kg ⁻¹ ·min ⁻¹ ). The highest mean VO 2 values attained in the CPET and verification phase were similar in the 54 studies that were meta-analyzed (mean difference = 0.03 [95% CI = -0.01 to 0.06] L/min, P = 0.15). Furthermore, the difference between the CPET and verification phase was not affected by any of the potential moderators such as verification phase intensity ( P = 0.11), type of recovery utilized ( P = 0.36), VO 2max verification criterion adoption ( P = 0.29), same or alternate day verification procedure ( P = 0.21), verification-phase duration ( P = 0.35), or even according to sex, cardiorespiratory fitness level, exercise modality, and CPET protocol ( P = 0.18 to P = 0.71). The funnel plot indicated that there was no significant publication bias. Conclusions The verification phase seems a robust procedure to confirm that the highest possible VO 2 has been attained during a ramp or continuous step-incremented CPET. However, given the high concordance between the highest mean VO 2 achieved in the CPET and verification phase, findings from the current study would question its necessity in all testing circumstances. PROSPERO Registration ID CRD42019123540.
... This is because cardiorespiratory fitness is related to functional capacity and has been shown to be a strong and independent predictor of all-cause and disease-specific mortality. This association is so strong that cardiorespiratory fitness is considered one of the key predictors of longevity [45]. The present programme's improvements in cardiorespiratory are supported by those of O'Brien et al. [33] whose 6-month, thrice-weekly, 90 min multimodal (aerobic, strength, balance, and flexibility training) programme using middle-aged participants was found to have increased their mean peak oxygen consumption (VO2peak) by a median of 0.56 mL.kg −1 .min ...
Article
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Non-communicable diseases (NCDs) are the leading cause of death globally, particularly impacting low-and middle-income countries and rural dwellers. Therefore, this programme aimed to investigate if a community-based mind-body PA programme implemented in a low-resource setting could improve health-related physical fitness outcomes. Black overweight or obese adult women (25 ± 4.7 years) with a body mass index (BMI) >25 kg.m −2 recruited from a rural settlement in South Africa with manifest risk factors for multimorbidity were assigned to a 10-week waiting-to-treat non-exercising control group (n = 65) or a community-based mind-body programme (n = 60) consisting of 45-60 min, thrice-weekly Tae-Bo. The intervention resulted in significant (p ≤ 0.05) improvements in body weight (p = 0.043), BMI (p = 0.037), and waist (p = 0.031) and hip circumferences (p = 0.040). Flexibility was found to be significantly increased at mid-and post-programme (p = 0.033 and p = 0.025, respectively) as was static balance (mid: p = 0.022; post: p = 0.019), hand grip strength (mid: p = 0.034; post: p = 0.029), sit-up performance (mid: p = 0.021; post: p = 0.018), and cardiorespiratory endurance (mid: p = 0.017; post: p = 0.011). No significant change was found in sum of skinfolds following the programme (p = 0.057). Such a community-based mind-body programme presents an opportunity to level health inequalities and positively improve health-related physical fitness in low-resource communities irrespective of the underlying barriers to participation .
... The result shows a mean increase of 12.9% in VO 2 peak with a clinical benefit of all-cause and disease-specific mortality. 6 Regarding 6 MWT, the field walk test documented a mean of 38.69% change. The increased 6 MWT distance postrehabilitation has been established objectively, as evidenced by the significant outcome. ...
Article
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Patients with post-acute COVID-19 symptoms (PACS) can present with significant sequela due to the complex systemic effects of COVID-19 infection. Most affected patients have persistent symptoms for 3-12 months after recovery from the acute phase of COVID-19. Dyspnea affecting activities of daily living is one of the most challenging symptoms and has led to an influx of pulmonary rehabilitation (PR) demand. Here we report the outcome of nine subjects with PACS who underwent 24 sessions of supervised pulmonary telerehabilitation. An improvised telerehabilitation PR was formulated to accommodate home confinement during the pandemic. Exercise capacity and pulmonary function were assessed using a cardiopulmonary exercise test, pulmonary function test, and St. George Respiratory Questionnaire (SGRQ). The clinical outcome shows improved exercise capacity on the 6-minute walk test for all patients, and most had improvement in VO2 peak and SGRQ. Seven patients improved in forced vital capacity and six in forced expiratory volume. PR is a comprehensive intervention for patients with chronic obstructive disease aimed at alleviating pulmonary symptoms and improving functional capacity. In this case series, we report its usefulness in patients with PACS and its feasibility when delivered as a supervised telerehabilitation program. Further support for the effectiveness of PR patients with PACS is mandated.
... Although VȮ 2 max is measured in liters per minute, it can be expressed as a weight-adjusted rate (ml·kg −1 ·min −1 ), which is more adequate to compare individuals with different body masses [7]. This measure is also influenced by body composition, which becomes worse with increasing fat mass and decreasing lean mass during the aging process [8]. ...
Article
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Performance in endurance sports decreases with aging, which has been primarily attributed to cardiovascular and musculoskeletal aging; however, there is still no clear information on the factors that are most affected by aging. The aim of this study was to compare two groups of runners (< 50 and > 50 years of age) according to their absolute, weight-adjusted maximal oxygen uptake (V̇O2max), lower limb lean mass-adjusted V̇O2max, ventilatory threshold, and respiratory compensation point (RCP). A total of 78 male recreational long-distance runners were divided into Group 1 (38.12 ± 6.87 years) and Group 2 (57.55 ± 6.14 years). Participants were evaluated for body composition, V̇O2max, VT, and RCP. Group 1 showed higher absolute and body mass-adjusted V̇O2max (4.60 ± 0.57 l·min-1 and 61.95 ± 8.25 ml·kg-1·min-1, respectively) than Group 2 (3.77 ± 0.56 l·min-1 and 51.50 ± 10.22 ml·kg-1·min-1, respectively), indicating a significant difference (p < 0.001, d = - 1.46 and p < 0.001, d = - 1.16). Correspondingly, Group 1 showed a significantly higher lower limb lean mass-adjusted V̇O2max (251.72 ± 29.60 ml·kgLM-1·min-1) than Group 2 (226.36 ± 43.94 ml·kgLM-1·min-1) (p = 0.008, d = - 0.71). VT (%V̇O2max) (p = 0.19, d = 0.19) and RCP (%V̇O2max) (p = 0.24, d = 0.22) did not differ between the groups. These findings suggest that both variables that are limited by central or peripheral conditions are negatively affected by aging, but the magnitude of the effect is higher in variables limited by central conditions. These results contribute to our understanding of how aging affects master runners.
... [12][13][14] Training strategies that are most effective in enhancing VȮ 2max are clinically relevant, as VȮ 2max is predictive of long-term survival. 15,16 However, substantially less is known regarding the effects of HIIT in cardiac rehabilitation on submaximal variables of exercise capacity. These variables are relevant, as their measurement does not rely on maximal effort and motivation of patients, and allow conclusions about the physiological and metabolic strain during exercise at a given intensity 17 and can be used to prescribe exercise intensities. ...
Article
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Here, we present evidence that replacement of half of the usually prescribed continuous exercise training sessions in cardiac rehabilitation with high-intensity interval training sessions affects these trajectories. High-intensity interval training shifts the nadirs of ventilatory equivalents for O2 and CO2 and the subsequent rise to load termination in cardiopulmonary exercise tests toward higher wattages. Surprisingly, however, the difference between training types does not show up in the trajectories of blood lactate concentrations, although they are thought to be based, at least in part, at least in part, on common physiological mechanisms. Thus, cardiopulmonary exercise tests (CPET) allow to detect adaptations to exercise training that are not detectable by measuring blood lactate concentrations. This underlines their importance in cardiac rehabilitation to detect training responses independent of maximally achieved values. In addition, we present a novel statistical approach of analyzing CPET and BLa data for scientific studies. In contrast to many previous studies, it does not rely on the determination of thresholds. The underlying idea was to circumvent the arbitrary application of any of the multiple (lactate) threshold concepts, which, as pointed out by Poole et al. (Poole DC, Rossiter HB, Brooks GA, Gladden LB. The anaerobic threshold: 50+ years of controversy. The Journal of physiology. 2021;599(3):737-67), “... attempt to describe a curve with a single data point” and therefore, in our view, constitute practical, yet overly simplistic summary measures. Instead, we statistically modelled the entire shape of the trajectories defining the relationship between both blood lactate concentrations and CPET parameters with power output. This allowed us to estimate and visualize how the entire curves changed due to training and allows to estimate group difference for any relative intensity.
... Most patients with NASH have a poor or very poor fitness level, independent of age, body mass index (BMI), and sex [11]. Cardiorespiratory fitness is predictive of mortality in the general population and in those with chronic disease, including NAFLD [12][13][14][15]. The HUNT study found all-cause mortality was increased 52% in NAFLD patients with low cardiorespiratory fitness compared to participants with high cardiorespiratory fitness [15]. ...
Article
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Background & Aims Cardiorespiratory fitness and liver fibrosis are independently associated with poor outcomes in patients with nonalcoholic steatohepatitis (NASH), however, conflicting reports exist about their relationship. We aimed to better characterize the relationship between cardiorespiratory fitness and liver histology in a cross-sectional study of patients with biopsy-proven NASH. Methods Participants aged 18–75 years completed VO2peak fitness assessment using symptom-limited graded exercise testing. Participants were compared by liver fibrosis stage and NAFLD Activity Score (NAS). Multivariable models were constructed to assess factors related to relative VO2peak, including liver fibrosis and NAS. Results Thirty-five participants with mean age 48 ± 12 years and body mass index 33.5 ± 7.6 kg/m² were enrolled. Seventy-four percent of participants were female and 49% had diabetes. A dose-dependent relationship was found between relative VO2peak and liver fibrosis. Relative VO2peak was significantly lower in participants with advanced fibrosis (F3 disease- 15.7 ± 5.3 vs. ≤ F2 disease- 20.7 ± 5.9 mL/kg/min, p = 0.027). NAS > 5 was also associated with lower relative VO2peak (22.6 ± 5.7 vs. 16.5 ± 5.1 mL/kg/min, p = 0.012) compared to NAS ≤ 5. With multivariable modeling, advanced fibrosis remained independently predictive of relative VO2peak while NAS trended towards significance. Discussion and Conclusions Advanced liver fibrosis is independently associated with cardiorespiratory fitness in patients with NASH. This may explain the incremental increase in mortality as liver fibrosis stage increases. Further research is needed to determine if exercise training can improve cardiorespiratory fitness across multiple stages of liver fibrosis and directly reduce morbidity and mortality in patients with NASH.
... In the current state, most molecular clocks are inferior to functional parameters to predict morbidity and mortality in humans (Fig. 4). Endurance and cardiovascular function (for exampleV O 2 max (Strasser & Burtscher, 2018), maximal endurance (Kodama et al., 2009) or daily steps (Paluch et al., 2022)), skeletal muscle function (for example muscle and grip strength (Sayer & Kirkwood, 2015), muscle power (Losa-Reyna et al., 2022) or muscle mass (Liu et al., 2022)) and neuromuscular function (for example gait speed (White et al., 2013)) all show strong prospective correlation with health. Importantly, these parameters represent at least part of the main decline in functional capacity with age that strongly contributes to loss of independence, hospitalization and admission to nursing homes (Nwagwu et al., 2020). ...
Article
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Ageing is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of major diseases, respectively. The genetic and molecular mechanisms that are involved in the regulation of the ageing process, and those that render age the main risk factor for many diseases are still poorly understood. Nevertheless, a growing number of compounds have been put forward to affect this process. However, for scientists and laypeople alike, it is difficult to separate fact from fiction, and hype from hope. In this review, we discuss the currently pursued pharmacological anti-ageing approaches. These are compared to non-pharmacological interventions, some of which confer powerful effects on health and well-being, in particular an active lifestyle and exercise. Moreover, functional parameters and biological clocks as well as other molecular marks are compared in terms of predictive power of morbidity and mortality. Then, conceptual aspects and roadblocks in the development of anti-ageing drugs are outlined. Finally, an overview on current and future strategies to mitigate age-related pathologies and the extension of life- and healthspan is provided.
... Good CRF protects people's health by reducing the development of noncommunicable diseases and decreasing associated risk factors (Tikkanen et al., 2018). In the cardiovascular system, it reduces cardiac stiffness, contributing to better blood distribution (Howden et al., 2018), which is associated with a lower incidence of heart failure (Kokkinos et al., 2019), in addition to maximizing mitochondrial respiration and increasing the eddectivity of blood distribution in the vascular system (Strasser & Burtscher, 2018). Furthermore, good CRF is directly related to the amount of time (minutes) spent in weekly physical activities/exercise. ...
Article
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Objective: To associate and compare the level of physical activity with cardiovascular health (CVH), quality of life, cardiorespiratory fitness, anthropometric variables and workload of active and sedentary women working in a university environment. Methods: Cross-sectional study, carried out with employees of a higher education institution. The sample was for convenience and 51 healthy adult women participated. Seven metrics were evaluated for CVH, using the international physical activity questionnaire and the Mediterranean diet questionnaire. Quality of life was assessed using the Short Form-36 instrument and cardiorespiratory fitness using the shuttle run test. The Student-t test and Mann-Whitney U test were used to analyze the data, and a multiple linear regression was performed with data adjusted for age and the climacteric period. Results: Active women had lower values for waist-hip ratio (WHR) (p=0.001) and diastolic blood pressure (DBP) (p<0.001), and higher results for maximal oxygen consumption (VO2max) (p<0.001), CVH score (p<0.001), functional capacity (p=0.004), and general health (p=0.009). There was a direct relationship with the CVH score (p= 0.018) and VO2max (p= 0.012), and an inverse relationship for workload (p=0.013). Conclusion: The level of physical activity contributes to lower values of risk factors for cardiovascular diseases (WHR and DBP) and higher values of VO2max, SCV scores and quality of life in active women.
... Low cardiorespiratory fitness (CRF) quantified as low maximal oxygen uptake (VO2max) is one of the most important risk factors for CVD and premature death, and suggested to be a stronger predictor of morbidity and mortality than established CVD risk factors like obesity, diabetes, smoking, and hypercholesterolemia (2). VO2max is also shown to a be strong and independent predictor of allcause and diseases-specific mortality (3). Low VO2max is shown to increase risk of dementia, cancer, and other lifestyle-related diseases (4,5). ...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Central Norway Regional Health Authority Norwegian Health Association Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide. Several studies have shown that low cardiorespiratory fitness (CRF) is a major risk factor for CVD and is suggested to be a stronger predictor of CVD morbidity and mortality than established cardiovascular risk factors. CRF quantified as maximal oxygen uptake (VO2max) has a strong genetic component, estimated to be ~50%. Unfortunately, current studies on genetic markers for CRF are limited by small sample sizes. In addition, there are few studies on directly measured VO2max, as most of the previous studies are based on estimated CRF. To overcome these limitations, we performed a large-scale systematic screening for genetic variants associated with VO2max aiming to provide awaited insight to this complex trait and discover possible links between VO2max and CVD. Purpose To identify and validate genetic factors associated with VO2max. Methods The genotypes of 70,000 participants from the Trøndelag Health study (HUNT) were imputed providing information on 25 million single-nucleotide polymorphisms (SNPs). We conducted a genome-wide association study (GWAS) including 4,525 participants with directly measured VO2max from the HUNT3 Fitness study. The GWAS was performed using BOLT-LMM, adjusted for age, gender, physical activity, principal components, and genotyping batch. In addition, we ran a GWAS with the same covariates except physical activity. Further, gender specific analyses were conducted. For validation, similar analyses were performed in the United Kingdom Biobank (UKBB). In the UKBB, CRF was assessed through a submaximal bicycle test. The analyses of UKBB included ~60,000 participants and over 90 million SNPs. Functional analyses of the GWAS results were examined by functional mapping and annotation (FUMA). Results Two GWAS-significant (p < 5×10-8) SNPs associated with VO2max were identified in the total population, two in the male population, and 24 in the female population in HUNT. Two of the 24 SNPs found in the female population were nominally significant in the UKBB. One of the validated SNPs in the female population is located inside PIK3R5, that is shown to be of importance in cardiac function and CVD. In addition, the functional analyses in the total- and male population revealed candidate SNPs in a gene previously found to be associated with endurance, PPP3CA. Conclusions We have identified 28 novel SNPs associated with VO2max in the HUNT cohort. Two of these SNPs were nominally validated in females in UKBB. One of the validated SNPs resides within a gene previously reported to be related to heart function and CVD. In addition, the functional analyses in the total- and male population revealed candidate SNPs in a gene previously found to be associated with endurance. Further functional analyses using bioinformatic approaches may provide more information on the physiological importance of these findings and their relation to CVD.
... Low cardiorespiratory fitness (CRF) quantified as low maximal oxygen uptake (VO2max) is one of the most important risk factors for CVD and premature death, and suggested to be a stronger predictor of morbidity and mortality than established CVD risk factors like obesity, diabetes, smoking, and hypercholesterolemia (2). VO2max is also shown to a be strong and independent predictor of allcause and diseases-specific mortality (3). Low VO2max is shown to increase risk of dementia, cancer, and other lifestyle-related diseases (4,5). ...
Article
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Central Norway Regional Health AuthorityNorwegian Health Association Introduction Cardiovascular disease (CVD) is the leading cause of death worldwide. Several studies have shown that low cardiorespiratory fitness (CRF) is a major risk factor for CVD. Low CRF is suggested to be a stronger predictor of CVD morbidity and mortality than established cardiovascular risk factors like obesity, diabetes, and cholesterol. Several studies suggest that CRF quantified as maximal oxygen uptake (VO2max) has a strong genetic component, estimated to be ~50%. Unfortunately, current studies on genetic markers for CRF are limited by small sample sizes. In addition, there are few studies on directly measured VO2max, as most of the previous studies are based on estimated CRF. Directly measured VO2max is considered as the gold standard for measuring CRF. Thus, a large-scale systematic screening for genetic variants associated with VO2max may provide awaited insight to this complex trait and discover possible links between VO2max and CVD. Purpose To identify and validate genetic factors associated with VO2max. Methods The genotypes of 70.000 participants from the Trøndelag Health study (HUNT) were imputed providing information on 25 million SNPs. We conducted a genome-wide association study (GWAS) including 4525 participants with directly measured VO2max from the HUNT3 Fitness study. The GWAS was performed using BOLT-LMM, adjusted for age, gender, physical activity, principal components, and genotyping batch. In addition, we ran a GWAS with the same covariates except physical activity. Further, gender specific analyses were conducted. For validation, similar analyses were performed in the United Kingdom Biobank (UKBB). In the UKBB, CRF was assessed through a submaximal bicycle test. The analyses of UKBB included ~60.000 participants and over 90 million SNPs. Results Two GWAS-significant (p < 5x10-8) SNPs associated with VO2max were identified in the total population in HUNT. Further, 24 GWAS-significant SNPs associated with VO2max in females, and two GWAS-significant SNPs associated with VO2max in males were discovered. Two of the 24 SNPs found in the female population were nominally significant in the UKBB. The validated SNPs are rs376927175, an intergenic SNP downstream of APBA1, and rs551942830 (proxy for rs190675254 with LD = 1.0), a 3 Prime UTR variant inside PIK3R5. PIK3R5 encodes the regulatory subunit of one class of PI3Ks, that is shown to be of importance in cardiac function and CVD. None of the SNPs found in the total population nor the male population were validated in UKBB. Conclusions We have identified 28 novel SNPs associated with VO2max in the HUNT cohort. Two of these SNPs were nominally validated in females in UKBB. One of the validated SNPs resides within a gene previously reported to be related to heart function and CVD. Further functional analyses using bioinformatic approaches may provide more information on the physiological importance of these findings and their relation to CVD.
... Low cardiorespiratory fitness (CRF) quantified as low maximal oxygen uptake (VO 2max ) is one of the most important risk factors for CVD and premature death, and is suggested to be a stronger predictor of morbidity and mortality than established CVD risk factors like obesity, diabetes, smoking, and hypercholesterolemia (2). TheVO 2max is also shown to a be strong and independent predictor of allcause and diseases-specific mortality (3). LowVO 2max is shown to increase risk of dementia, cancer, and other lifestyle-related diseases (4,5). ...
Article
Purpose: Low cardiorespiratory fitness (CRF) is a major risk factor for CVD and a stronger predictor of CVD morbidity and mortality than established risk factors. The genetic component of CRF, quantified as peak oxygen uptake (VO2peak), is estimated to be ~60%. Unfortunately, current studies on genetic markers for CRF have been limited by small sample sizes and using estimated CRF. To overcome these limitations, we performed a large-scale systematic screening for genetic variants associated with VO2peak. Methods: A genome-wide association study (GWAS) was performed with BOLT-LMM including directly measured VO2peak from 4,525 participants in the HUNT3 Fitness study and 14 million single-nucleotide polymorphisms (SNPs). For validation, similar analyses were performed in the United Kingdom Biobank (UKB), where CRF was assessed through a submaximal bicycle test, including ~60,000 participants and ~ 60 million SNPs. Functional mapping and annotation of the GWAS results was conducted using FUMA. Results: In HUNT, two genome-wide significant SNPs associated with VO2peak were identified in the total population, two in males, and 35 in females. Two SNPs in the female population showed nominally significant association in the UKB. One of the replicated SNPs is located in PIK3R5, shown to be of importance for cardiac function and CVD. Bioinformatic analyses of the total and male population revealed candidate SNPs in PPP3CA, previously associated with CRF. Conclusions: We identified 38 novel SNPs associated with VO2peak in HUNT. Two SNPs were nominally replicated in UKB. Several interesting genes emerged from the functional analyses, among them one previously reported to be associated with CVD and another with CRF.
... The Cooper test was performed by running on a treadmill (Precor 966i, USA) for 12 min, and VO2max was calculated from the distance covered by running in this period of time (Tanaka et al 2000). According to the calculated VO2max expressed as ml/kg/min, the subjects were assigned to one of 5 categories of physical fitness (Strasser 2018): ...
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Purpose The effects of aerobic exercise on bone metabolism are still unclear. Thus, the main goal of this study was to explore if there was an effect of the short-term aerobic exercise program on the bone remodeling process and if there were sex differences in the effect of the training program on bone metabolism. Methods Twenty-one participants (men and women) aged 20–23 performed an 8-week aerobic exercise program three times per week in 1-h sessions with increases in the exercise load every 2 weeks. Bone density, bone mineral content and concentration of markers of bone metabolism: osteocalcin, C-terminal procollagen type I peptide, pyridinoline, parathyroid hormone, osteoprotegerin, and the receptor activator of nuclear kappa B ligand by ELISA were measured at the start and at the end of the study, while changes in body composition were assessed by a bioelectric impedance analysis method 6 times during the study. Results The aerobic exercise program increased the concentration of osteocalcin (11.34 vs 14.24 ng/ml), pyridinoline (67.51 vs 73.99 nmol/l), and the receptor activator of nuclear kappa B ligand (95.122 vs 158.15 pg/ml). A statistically significant increase in bone density at neck mean (1.122 vs 1.176 g/cm³) and in bone mineral content at dual femur (33.485 vs 33.700 g) was found in women, while there was no statistically significant change at any site in men. Conclusion 8 weeks of the aerobic exercise program with increment in intensity increased some of bone remodeling biomarkers and showed different effects for men and women.
... It is important to recognise the integrative pathophysiological processes following COVID-19 infection and subsequent long-COVID. Cardiorespiratory fitness is a key predictor of functional capacity, quality of life, and a strong predictor of mortality [73,74]. Aerobic capacity, quantified by maximal oxygen consumption (VO 2peak ), and ventilatory efficiency, is quantified by the minute ventilation/carbon dioxide production (VE/VCO 2 ) slope, are two established measures obtained through cardio-pulmonary exercise testing and several initial studies to date have reported the impact of COVID-19 on both [75]. ...
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Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) transmission continues to impact people globally. Whilst the acute symptoms and management strategies are well documented, millions of people globally are experiencing a prolonged and debilitating symptom profile that is reported to last months and even years. COVID-19 is a multi-system disease however the magnitude of the effects and its associated legacy is presently not well understood. Early reports indicate that multidisciplinary approaches between clinical and non-clinical entities are needed to provide effective and rehabilitative patient support pathways and restore pre-COVID-19 quality of life and functional status. Accordingly, this review provides a summary of the impact on cardiovascular, inflammatory, respiratory, and musculoskeletal function following an acute COVID-19 infection along with the prolonged effects of long-COVID.
... Aerobic training improves body composition, the functioning of the cardiovascular system, the cardiovascular lipid profile and insulin sensitivity 3 . Importantly, aerobic training increases aerobic fitness (VO2max) 3 , which is an independent predictor of health and protects against a range of chronic conditions including type 2 diabetes and cardiovascular disease 4 . Resistance training increases total muscle mass, muscle strength and power, neuromuscular firing rate 5 and recruitment and functioning of the fast twitch type 2 fibers which deteriorate with age 6 . ...
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Middle-aged (50-64yrs) and older adults (65-90yrs) in Laois predominantly undertook sufficient aerobic activities to improve health, but most did not meet the guidelines for resistance, balance or flexibility training. Thus, educating middle-aged and older adults on the benefits of multimodal PA and providing enjoyable opportunities for both populations within the community that focus on social inclusion is required.
... Indeed, even short distance travel by walking and cycling (less than 3 km) [20], shows little evidence to the effectiveness of active transport interventions for reducing obesity [21]. Higher relative VO2max values are associated with greater life expectancy [22]. ...
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Marathon running leaves a significant carbon footprint regarding CO2 emissions; for example, 37 percent of New York Marathon participants travel internationally to New York. The aim of this study is to estimate the CO2 footprint of a person training and competing in a marathon; we will also propose methods to minimize the CO2 footprint because of transportation. In addition, we also examine the influence of food practices and hygiene on training and racing a marathon. Methods: We estimated the annual carbon footprint of one person taking part in a marathon. We considered all training, racing, and travelling (local and international) for one person (we are going to give him the first name of "Henri"), and then compared his CO2 footprint with his colleagues playing tennis and soccer. The excess CO2 footprint whilst running and for shoes, clothing, books, magazines, insurance, travel, hygiene, laundry, and resources for electronics and additional food consumed were calculated. For competitions, we estimated and compared the CO2 emission from transportation to national vs. international marathon (New York). Results: We estimated that our runner emitted 4.3 tons of CO2 equivalent (CO2e), including all greenhouse gases. A transatlantic flight to New York corresponded to 3.5 tons CO2, which is 83% of the annual carbon footprint of an average French citizen which is about 11 tons CO2e/year. This leads to a sudden 40% increase in Henri's annual carbon footprint. Conclusions: By focusing on the additional carbon footprint from one year of marathon training and racing, and traveling locally versus internationally, this sport still has a potentially significant carbon footprint that runners and race organizers ought to consider. We wanted to answer a growing question of marathon runners who are wondering about the carbon footprint of their sports practice in following with a new environmentalist trend that considers not traveling anymore to participate in marathons and to stay local. However, the representativeness in the selection of calculation objectives is very low. There is no need for statistics since this study is a theoretical simulation of traditional training and competition practices of marathon runners.
... In the exercise physiology literature, two objective measures include maximal aerobic capacity V O 2max and aerobic economy [26,27].V O 2max represents the maximal amount of oxygen that can be consumed during exhaustive exercise, where a higherV O 2max is indicative of greater cardiorespiratory fitness. Aerobic economy represents the steady-state energy requirement of exercise conducted at a constant exercise intensity (e.g., running at a constant velocity). ...
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Objectives: Researchers have begun delivering mindfulness and aerobic exercise training concurrently on the premise that a combination intervention will yield salutary outcomes over and above each intervention alone. An estimate of the effect of combination training on chronic psychosocial stress in a nonclinical population has not been established. The objective of this study was to establish protocol feasibility in preparation of a definitive RCT targeting healthy individuals, and to explore the preliminary effect of combination training on reducing chronic psychosocial stress in this population. Methods: Twenty-four participants were allocated to a single-arm pre-post study and subjected to 16 weeks of concurrent mindfulness psychoeducation and aerobic exercise training. Feasibility criteria were collected and evaluated. Within-group changes in chronic psychosocial stress, mindfulness, emotion regulation, and cardiorespiratory fitness were also assessed. Primary analyses were based on 17 participants. Results: Retention rate, response rate, recruitment rate, and sample size analyses indicate a definitive trial is feasible for detecting most effects with precision. There was also a decline in our primary dependent measure of chronic psychosocial stress (dpretest = -0.56, 95% CI [ -1.14,-0.06]). With regard to secondary measures, there was an increase in the use of cognitive reappraisal, and a reduction in use of maladaptive emotion regulation strategies. We are insufficiently confident to comment on changes in mindfulness and aerobic capacity [Formula: see text]. However, there were subgroup improvements in aerobic economy at submaximal exercise intensities. Conclusions: We recommend a definitive trial is feasible and should proceed. Trial registration: ANZCTR (ID: ACTRN12619001726145 ). Retrospectively registered December 9, 2019.
... For every 10% decrease in VO 2max , there is a 15% increase in overall mortality [24]. CRF also predicts mortality in persons with chronic disease, including NAFLD [5,25,26]. The HUNT study demonstrated a 52% increased risk of all-cause mortality over a mean follow-up of 9.4 years in 15,781 NAFLD subjects with low CRF [5•]. ...
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Purpose of Review Nonalcoholic fatty liver disease (NAFLD) is a leading cause of global liver disease. Because current pharmacologic treatments are ineffective, lifestyle change centered on exercise remains the most effective NAFLD treatment. The aim of this systematic review is to summarize and evaluate the current evidence supporting the use of exercise training as a medical treatment for adult patients with NAFLD. Recent Findings At least 150 min each week of moderate intensity exercise of any type can improve NAFLD, both with and without modest weight loss. Exercise training reduces hepatic steatosis and liver inflammation, favorably changes body composition, improves vascular endothelial function, increases cardiorespiratory fitness, and can lead to histologic response. To date, exercise-based NAFLD trials are limited by small sample size and significant heterogeneity. Summary While several key questions remain unanswered, exercise training will always be an important part of the medical management of patients with NAFLD.
... A greater physical fitness relates to a better prognosis and (disability-free) life expectancy in many different cohorts of patients and in healthy individuals [30]). The physical fitness actually is prognostically more important than adiposity in obese individuals [31]. ...
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Although there is growing evidence on the importance of physical activity and exercise intervention after bariatric surgery, it remains to be clarified as to why and how post-operative exercise intervention should be implemented. In this narrative and practically oriented review, it is explained why exercise interventions and physical activity are important after bariatric surgery, how to prescribe exercise and monitor physical activity and how and when physical fitness, muscle strength, fat (-free) mass and bone mineral density could be assessed during follow-up. It is suggested that the inclusion of physical activity and exercise training in the clinical follow-up trajectory could be of great benefit to bariatric surgery patients, since it leads to greater improvements in body composition, bone mineral density, muscle strength and physical fitness.
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Objective There is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake ( V ˙ O 2 m a x ) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and V ˙ O 2 m a x . Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and V ˙ O 2 m a x (absolute and relative V ˙ O 2 m a x ) among both observational and interventional studies. Methods A systematic search was performed on December 6 th , 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and V ˙ O 2 m a x values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and V ˙ O 2 m a x values. For interventional studies, meta-analysis models were performed to determine the change in V ˙ O 2 m a x values (standard paired difference) associated with interventions designed to modify hemoglobin levels or V ˙ O 2 m a x . Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in V ˙ O 2 m a x values. Results Data from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute V ˙ O 2 m a x and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit ( P <0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute V ˙ O 2 m a x (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration ( P <0.0001) and hemoglobin mass ( P = 0.006)). Conclusion These findings suggest that V ˙ O 2 m a x values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.
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Background: Oxygen consumption is an important index to evaluate in cardiac patients, particularly those with heart failure, and is measured in the setting of advanced cardiopulmonary exercise testing. However, technological advances now allow for the estimation of this parameter in many consumer and medical-grade wearable devices, making it available for the medical provider at the initial evaluation of patients. We report a case of an apparently healthy male aged 40 years who presented for evaluation due to an Apple Watch (Apple Inc) notification of low cardiac fitness. This alert triggered a thorough workup, revealing a diagnosis of familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. While the use of wearable devices for the measurement of oxygen consumption and related parameters is promising, further studies are needed for validation. Objective: The aim of this report is to investigate the potential utility of wearable devices as a screening and risk stratification tool for cardiac fitness for the general population and those with increased cardiovascular risk, particularly through the measurement of peak oxygen consumption (VO2). We discuss the possible advantages of measuring oxygen consumption using wearables and propose its integration into routine patient evaluation and follow-up processes. With the current evidence and limitations, we encourage researchers and clinicians to explore bringing wearable devices into clinical practice. Methods: The case was identified at Sheba Medical Center, and the patient's cardiac fitness was monitored through an Apple Watch Series 6. The patient underwent a comprehensive cardiac workup following his presentation. Subsequently, we searched the literature for articles relating to the clinical utility of peak VO2 monitoring and available wearable devices. Results: The Apple Watch data provided by the patient demonstrated reduced peak VO2, a surrogate index for cardiac fitness, which improved after treatment initiation. A cardiological workup confirmed familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. A review of the literature revealed the potential clinical benefit of peak VO2 monitoring in both cardiac and noncardiac scenarios. Additionally, several devices on the market were identified that could allow for accurate oxygen consumption measurement; however, future studies and approval by the Food and Drug Administration (FDA) are still necessary. Conclusions: This case report highlights the potential utility of peak VO2 measurements by wearable devices for early identification and screening of cardiac fitness for the general population and those at increased risk of cardiovascular disease. The integration of wearable devices into routine patient evaluation may allow for earlier presentation in the diagnostic workflow. Cardiac fitness can be serially measured using the wearable device, allowing for close monitoring of functional capacity parameters. Devices need to be used with caution, and further studies are warranted.
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This study aims to determine the effect of motivation, self-confidence, and maximum oxygen consumption on the basic skills of playing soccer. This research includes path analysis research (path analysis). Exogenous variables are motivation (x1), confidence (x2), and maximum oxygen consumption (x3), while endogenous variables are the basic skills of playing soccer. The sample of this research was 100 male students of class XI MAN 2 Bone. Data were analyzed by inferential statistical analysis, namely the regression test. The findings showed that motivation (MTV), self-confidence (PD), and maximum oxygen ability (VO2 max) affected the basic skills of playing soccer (KSB) (p<0.05). This study only involved a small sample, so the findings of this study can still be developed for further research using more methods or samples.
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Background and aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD. Approach and results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD.
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Background Maximal oxygen uptake and muscle strength are fundamental components of physical fitness. Improving these capacities is highly beneficial to health. The validity of maximal oxygen uptake and muscle strength has been widely emphasized in clinical, sports, and research-related settings. However, many of the previous tests required special equipment and space. Aim This study examined the effectiveness of field tests that do not require special equipment or space. Materials and methods The relationship between the 3-minute burpee test (3MBT) and estimated maximal oxygen uptake (Yo-Yo intermittent recovery test (Yo-Yo IRT)) using whole-body muscle groups was examined. The subjects were young men (n=127) with a history of exercising at least once a week. Results A strong relationship between 3MBT and Yo-YoIRT was shown (p<0.001). Conclusions The 3MBT is a field test that can be performed anytime and anywhere there is space for plank and standing postures. Because it is very brief, efficient, and uses muscle groups throughout the body, it is effective and potentially quite useful as a new field test.
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Physical activity (PA) is a key component for brain health and Reserve, and it is among the main dementia protective factors. Robertson proposed that the upregulation of Locus Coeruleus-noradrenergic (LC-NA) system might be a key aspects for building reserve and resilience to neurodegeneration. PA elicits an enhanced catecholamine response, in particular Noradrenaline (NA). By increasing physical commitment, greater amount NA is synthetised in response to higher oxygen demand. More trained individuals show greater capabilities to carry oxygen resulting in greater Vo2max (a measure of oxygen uptake and physical tness indicator). In the current study, we hypothesised that greater Vo2 max could be related to greater LC-NA MRI integrity. As hypothesised, greater Vo2max related to greater LC integrity across 41 healthy adults (age range 60-72). As a control procedure, when the analyses were repeated for the other neuromodulators' seeds (Serotonin, Dopamine and Acetylcholine) weaker associations emerged. The newly established link between Vo2max and LC-NA system offers further understanding of the neurobiology underpinning Reserve in relationship to PA. While this study supports Robertson's theory proposing the upregulation of the noradrenergic system as a possible key factor building Reserve, it also provide ground for increasing LC-NA system resilience to neurodegeneration via Vo2max enhancement.
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Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength, to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial and error" approach with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and inter-individual differences in exercise capacity and performance, with special considerations given to the ageing athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise, and how such adaptations translate from "molecules to medals".
Thesis
Cette thèse avait pour ambition de contribuer à la compréhension des effets des variables de contrôle sur la performance, que sont le temps, la vitesse, la perception de l'effort (article 1), la distance (article 2) ainsi que V̇O2 et la fréquence cardiaque (article 3). Nous avons pu réaliser ce travail en utilisant les nouvelles possibilités qu'offrent les nouvelles technologies affranchissant le physiologiste du tapis roulant tout en disposant de la possibilité de contrôler par Bluetooth® toutes les variables physiologiques. Nous avons mis en évidence que : 1) les athlètes étaient capables d'adapter et de reproduire des réponses physiologiques non seulement en intensité mais en durée (article 1), 2) lorsque la variable de contrôle est la distance avec une mise en situation de compétition, la contribution de l'énergie à V̇O2max était relativement identique en proportion de l'énergie aérobie et ce, du 100 au 10,000m (article 2). Il y aurait donc un continuum énergétique allant du sprint au 10 kilomètres qui pourrait être une information intégrée dans l'organisme de façon centrale (demi-fond et fond) ou métabolique (sprint), 3) Enfin, nous avons montré que même dans un effort assez long (12 minutes) et maximal, le coureur tirait bénéfice d'une aide de contrôle « physiologique » par la fréquence cardiaque ou V̇O2 pour parvenir à sa meilleure performance. En conclusion, ce travail de thèse propose une méthodologie dans laquelle le coureur devient autonome dans le choix de sa stratégie de vitesse en s'affranchissant des calculs de vitesse cible à partir des seuils physiologiques, V̇O2max et autres facteurs physiologiques rendus limitants en cela.
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The aim of this systematic review and meta-analysis was to evaluate the association between glycemic control (HbA1c) and functional capacity (VO2max) in individuals with type 1 diabetes (T1DM). A systematic literature search was conducted in EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and ISI Web of Knowledge for publications from January 1950 until July 2020. Randomized and observational controlled trials with a minimum number of three participants were included if cardio-pulmonary exercise tests to determine VO2maxand HbA1c measurement has been performed. Pooled mean values were estimated for VO2maxand HbA1c and weighted Pearson correlation and meta-regression were performed to assess the association between these parameters. We included 187 studies with a total of 3278 individuals with T1DM. The pooled mean HbA1c value was 8.1% (95%CI; 7.9–8.3%), and relative VO2maxwas 38.5 mL/min/kg (37.3–39.6). The pooled mean VO2maxwas significantly lower (36.9 vs. 40.7, p = 0.001) in studies reporting a mean HbA1c >7.5% compared to studies with a mean HbA1c ≤7.5%. Weighted Pearson correlation coefficient was r = −0.19 (p < 0.001) between VO2maxand HbA1c. Meta-regression adjusted for age and sex showed a significant decrease of −0.94 mL/min/kg in VO2maxper HbA1c increase of 1% (p = 0.024). In conclusion, we were able to determine a statistically significant correlation between HbA1c and VO2maxin individuals with T1DM. However, as the correlation was only weak, the association of HbA1c and VO2maxmight not be of clinical relevance in individuals with T1DM.
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Physical inactivity is the fourth leading global cause of death and is a major contributor to metabolic and endocrine diseases. In this review we provide a current update of the past 5 years in the field as it pertains to the most prevalent and deadly chronic diseases. Despite the prevalence of physical inactivity in modern society, it remains largely overlooked relative to other comparable risk factors such as obesity, and our molecular understanding of how physical inactivity impacts metabolism is still partially unknown. Therefore, we discuss current clinical inactivity models along with their most recent findings regarding health outcomes along with any discrepancies that are present in the field. Lastly, we discuss future directions and the need for translatable animal models of physical inactivity to discover novel molecular targets for the prevention of chronic disease.
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Elite masters endurance athletes are considered models of optimal healthy aging due to the maintenance of high cardiorespiratory fitness (CRF) until old age. Whereas a drop in VO2max in masters athletes has been broadly investigated, the modifying impact of training still remains a matter of debate. Longitudinal observations in masters endurance athletes demonstrated VO2max declines between −5% and −46% per decade that were closely related to changes in training volume. Here, using regression analyses, we show that 54% and 39% of the variance in observed VO2max decline in male and female athletes, respectively is explained by changes in training volume. An almost linear VO2max decrease was observed in studies on young and older athletes, as well as non-athletes, starting a few days after training cessation, with a decline of as much as −20% after 12 weeks. Besides a decline in stroke volume and cardiac output, training cessation was accompanied by considerable reductions in citrate synthase and succinate dehydrogenase activity (reduction in mitochondrial content and oxidative capacity). This reduction could largely be rescued within similar time periods of training (re)uptake. It is evident that training reduction or cessation leads to a considerably accelerated VO2max drop, as compared to the gradual aging-related VO2max decline, which can rapidly nullify many of the benefits of preceding long-term training efforts.
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Introduction: The genetic disorder causing Down syndrome (DS) affects the cardiorespiratory and hemodynamic parameters. When exercising, sufficient blood flow is necessary for active muscles. Cardiac output (Q) must be proportional to the peripheral requirements. In case the stroke volume (SV) is lower, the heart rate (HR) will increase further in order to maintain an adequate blood flow in the active territories (HR compensatory response). People with DS have a lower HR response to maximal exercise. Nevertheless, the response of the hemodynamic and cardiorespiratory parameters during the submaximal phases of maximal exercise was not well studied. Objective: to evaluate cardiorespiratory and hemodynamic parameters 1) during submaximal and 2) maximal metabolic treadmill test in individuals with and without DS. Methods: fifteen adults with DS (age = 27.33 ± 4.98 years old; n = 12 males/3 females) and 15 adults without disabilities, matched by age and sex, participated in this cross-sectional study. Peak and submaximal cardiorespiratory and hemodynamic parameters were measured during a treadmill test. Linear mixed-effects models were used to analyse interactions between the variables. Post-hoc analyses were employed to assess within and between-group differences. Results: The DS group showed lower peak values for ventilation (VE), respiratory exchange ratio (RER), tidal volume (V T ), ventilatory equivalent for O 2 (VEqO 2 ), end-tidal partial pressure for O 2 (P ET O 2 ), O 2 uptake (VO 2 ) and CO 2 production (all p < 0 .050), Q, SV, systolic and diastolic blood pressure (SBP, DBP), and HR (all p < 0 .050). There were group-by-time interactions (all p < 0 .050) for all ventilatory submaximal values. Significant group and time differences were observed for VE; RER; respiratory rate (RR); VEqO 2 ; P ET O 2 ; VO 2, and V T (all p < 0 .050). There were also group-by-time interactions (all p < 0 .050) and group and time differences for SBP, mean arterial blood pressure (MAP) and HR (all p < 0.010). Conclusion: During submaximal exercise, we verified a compensatory response of HR, and greater VE and VO 2 in the individuals with DS. In addition, we were able to observe that the DS group had a reduced SBP and MAP response to submaximal exercise. On the other hand, we found that adults with DS have lower peak hemodynamic and cardiorespiratory values, and a lower cardiac reserve. Further research is warranted to investigate the effects of these results on the general health of adults with DS and the impact of long-term exercise programs on these parameters.
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Introdução: A prática de corrida é uma importante estratégia para o indivíduo tornar-se fisicamente ativo, entretanto muitos praticam de forma recreacional e sem supervisão profissional, neste sentido a literatura carece de estudos sobre os efeitos sobre esta prática de exercícios para a saúde cardiovascular. Objetivo: Avaliar a influência da corrida recreativa na capacidade cardiorrespiratória em mulheres adultas. Materiais e Métodos: Neste estudo descritivo, comparativo e quase-experimental, a amostra foi composta por 60 mulheres adultas distribuídas em dois grupos: Grupo Não Praticantes (n=29), com idade de (33,17 ± 11,58 anos) e Grupo Praticantes (n=31), com idade de (40,1 ± 10,5 anos). Após avaliação da massa corporal e estatura, foi calculado o índice de massa corporal das participantes. Em seguida, ambos os grupos foram submetidos ao teste de esteira para avaliar a capacidade cardiorrespiratória. A frequência cardíaca e a percepção subjetiva de esforço (0 a 10) foram monitoradas durante todo o teste. Resultados: Em relação ao índice de massa corporal não foram encontradas diferenças significativas entre os grupos. Quanto ao teste de capacidade cardiorrespiratória os resultados foram estatisticamente maiores no grupo praticantes em relação ao grupo não praticantes. Conclusão: A corrida recreativa melhora capacidade cardiorrespiratória contribuindo para prevenção de doenças e proteção a saúde de mulheres de meia idade.
Article
Mechanosensors control muscle integrity as demonstrated in mice. However, no information is available in human muscle about the distribution of mechanosensors and their adaptations to mechanical loading and environmental conditions (hypoxia). Here, we hypothesized that mechanosensors show fiber‐type‐specific distributions and that loading and environmental conditions specifically regulate mechanosensors. We randomly subjected 28 healthy males to one of the following groups (n = 7 each) consisting of nine loading sessions within 3 weeks: normoxia moderate (NM), normoxia intensive (NI), hypoxia moderate (HM), and hypoxia intensive (HI). We took six biopsies: pre (T0), 4 h (T1), and 24 h (T2) after the third as well as 4 h (T3), 24 h (T4), and 72 h (T5) after the ninth training session. We analyzed subjects' maximal oxygen consumption (V̇O2max), maximal power output (Pmax), muscle fiber types and cross‐sectional areas (CSA), fiber‐type‐specific integrin‐linked kinase (ILK) localizations as well as ILK, vinculin and talin protein and gene expressions in dependence on loading and environmental conditions. V̇O2max increased upon NM and HM, Pmax upon all interventions. Fiber types did not change, whereas CSA increased upon NI and HI, but decreased upon HM. ILK showed a type 2‐specific fiber type localization. ILK, vinculin, and talin protein and gene expressions differed depending on loading and environmental conditions. Our data demonstrate that mechanosensors show fiber type‐specific distributions and that exercise intensities rather than environmental variables influence their profiles in human muscles. These data are the first of their kind in human muscle and indicate that mechanosensors manage the mechanosensing at a fiber‐type‐specific resolution and that the intensity of mechanical stimulation has a major impact.
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Background A negative impact of premature birth on health in adulthood is well established. However, it is not clear whether healthy adults who were born prematurely but have similar physical activity levels compared to adults born at term have a reduced maximal aerobic exercise capacity (maximum oxygen consumption [VO2max]). Objective We aimed to determine the effect of premature birth on aerobic exercise capacity and lung function in otherwise healthy, physically active individuals. Methods A broad literature search was conducted in the PubMed database. Search terms included ‘preterm/premature birth’ and ‘aerobic exercise capacity’. Maximal oxygen consumption (mL/kg/min) was the main variable required for inclusion, and amongst those investigations forced expiratory volume in 1 s (FEV1, % predicted) was evaluated as a secondary parameter. For the systematic review, 29 eligible articles were identified. Importantly, for the meta-analysis, only studies which reported similar activity levels between healthy controls and the preterm group/s were included, resulting in 11 articles for the VO2max analysis (total n = 688, n = 333 preterm and n = 355 controls) and six articles for the FEV1 analysis (total n = 296, n = 147 preterm and n = 149 controls). Data were analysed using Review Manager ( Review Manager. RevMan version 5.4 software. The Cochrane Collaboration; 2020.). Results The systematic review highlighted the broad biological impact of premature birth. While the current literature tends to suggest that there may be a negative impact of premature birth on both VO2max and FEV1, several studies did not control for the potential influence of differing physical activity levels between study groups, thus justifying a focused meta-analysis of selected studies. Our meta-analysis strongly suggests that prematurely born humans who are otherwise healthy do have a reduced VO2max (mean difference: − 4.40 [95% confidence interval − 6.02, − 2.78] mL/kg/min, p < 0.00001, test for overall effect: Z = 5.32) and FEV1 (mean difference − 9.22 [95% confidence interval − 13.54, − 4.89] % predicted, p < 0.0001, test for overall effect: Z = 4.18) independent of physical activity levels. Conclusions Whilst the current literature contains mixed findings on the effects of premature birth on VO2max and FEV1, our focused meta-analysis suggests that even when physical activity levels are similar, there is a clear reduction in VO2max and FEV1 in adults born prematurely. Therefore, future studies should carefully investigate the underlying determinants of the reduced VO2max and FEV1 in humans born preterm, and develop strategies to improve their maximal aerobic capacity and lung function beyond physical activity interventions.
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A poor Fitness Fatness Index (FFI) is associated with type 2 diabetes incidence, other chronic conditions (Alzheimer’s, cancer, and cardiovascular disease) and all-cause mortality. Recent investigations have proposed that an individualised exercise prescription based on ventilatory thresholds is more effective than a standardised prescription in improving cardiorespiratory fitness (CRF), a key mediator of FFI. Thus, the aim of the current study was to determine the effectiveness of individualised versus standardised exercise prescription on FFI in sedentary adults. Thirty-eight sedentary individuals were randomised to 12-weeks of: (1) individualised exercise training using ventilatory thresholds (n = 19) or (2) standardised exercise training using a percentage of heart rate reserve (n = 19). A convenience sample was also recruited as a control group (n=8). Participants completed CRF exercise training three days per week, for 12-weeks on a motorised treadmill. FFI was calculated as CRF in metabolic equivalents (METs), divided by fatness determined by waist to height ratio (WtHR). A graded exercise test was used to measure CRF, and anthropometric measures (height and waist circumference) were assessed to ascertain WtHR. There was a difference in FFI change between study groups, whilst controlling for baseline FFI, F (2, 42) = 19.382 p < .001, partial η2 = 0.480. The magnitude of FFI increase from baseline was significantly higher in the individualised (+15%) compared to the standardised (+10%) (p = 0.028) and control group (+4%) (p = <.001). The main finding of the present study is that individualised exercise prescription had the greatest effect on improving FFI in sedentary adults compared to a standardised prescription. Therefore, an individualised based exercise prescription should be considered a viable and practical method of improving FFI in sedentary adults.
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We analyzed whether male Spanish elite soccer players live longer than the general population. Secondly, we compared their mortality with a cohort of soccer players who continued working as soccer elite coaches after retirement. Using age and calendar-date adjusted life tables, we analyzed the mortality hazard ratio of 1333 Spanish male players born before 1950, and who played in elite leagues from 1939, compared with the Spanish population. Using Cox proportional hazards model we compared their mortality with a cohort of 413 players who continued as coaches. Players showed significantly lower mortality than the general population, but this advantage decreased with advanced age, disappearing after 80 years. Coaches showed a similar pattern. Comparing players versus coaches, date of birth and years as professional were associated with survival, but debut age and player position were not. Unadjusted median survival time was 79.81 years (IQR 72.37–85.19) for players and 81.8 years (IQR 74.55–86.73) for coaches. Kaplan-Meier estimator adjusted for covariables showed no difference between cohorts (p=0.254). In conclusion, former Spanish male players showed lower mortality than the general population, but this effect disappeared after 80 years of age. Continuing their career as coaches after retirement from playing did not confer major benefits.
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Un des enjeux majeurs nationaux de santé publique se joue à l'école primaire. Pratiquer tous les jours, dedans ou dehors, reste un objectif recommandé par les autorités de santé, pour enrayer les effets délétères de la sédentarité. Si les habitudes d'activité physique (AP) chez les adolescents et jeunes adultes sont documentés, celles concernant les enfants en école primaire restent encore mal connues. Quelques rares études mentionnent une baisse continue de la quantité d'AP depuis la seconde moitié du 20ème siècle, concomitant à une dégradation de leur capacités cardiorespiratoires. Il en découle ainsi, chez les enfants, la question des relations entre sédentarité, AP et EPS à l'école primaire. Si l'école est parfois le seul lieu de pratique d'AP pour les enfants, des rapports parlementaires ont souligné l'insuffisance des horaires effectifs d'EPS au regard des programmes de l’Éducation Nationale et les contraintes inhérentes à l'EPS aux cycles 1, 2 et 3. Au-delà de ce premier constat, nous tentons d'apporter quelques pistes pédagogiques à l'intention des Professeurs des Écoles pour maximiser la durée d'activité réelle des élèves.
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Background: Transcripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Methods: We analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-⍺-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to a high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. Results: We find that: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and a high-fat diet increase RE expression; and 2) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Conclusions: RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
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PurposeTo examine the influence of post-exercise protein feeding upon the adaptive response to endurance exercise training.Methods In a randomised parallel group design, 25 healthy men and women completed 6 weeks of endurance exercise training by running on a treadmill for 30–60 min at 70–75% maximal oxygen uptake (VO2max) 4 times/week. Participants ingested 1.6 g per kilogram of body mass (g kg BM−1) of carbohydrate (CHO) or an isocaloric carbohydrate–protein solution (CHO-P; 0.8 g carbohydrate kg BM−1 + 0.8 g protein kg BM−1) immediately and 1 h post-exercise. Expired gas, blood and muscle biopsy samples were taken at baseline and follow-up.ResultsExercise training improved VO2max in both groups (p ≤ 0.001), but this increment was not different between groups either in absolute terms or relative to body mass (0.2 ± 0.2 L min−1 and 3.0 ± 2 mL kg−1 min−1, respectively). No change occurred in plasma albumin concentration from baseline to follow-up with CHO-P (4.18 ± 0.18 to 4.23 ± 0.17 g dL−1) or CHO (4.17 ± 0.17 to 4.12 ± 0.22 g dL−1; interaction: p > 0.05). Mechanistic target of rapamycin (mTOR) gene expression was up-regulated in CHO-P (+ 46%; p = 0.025) relative to CHO (+ 4%) following exercise training.Conclusion Post-exercise protein supplementation up-regulated the expression of mTOR in skeletal muscle over 6 weeks of endurance exercise training. However, the magnitude of improvement in VO2max was similar between groups.
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Transcripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and age-accelerating treatments increase RE expression; and 2) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Thus, RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
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Cardiorespiratory fitness, as assessed through peak oxygen uptake (VO2peak), is a powerful health indicator. We aimed to evaluate the influence of several candidate causal genetic variants on VO2peak level in untrained Han Chinese people. A total of 1009 participants (566 women; age [mean ± SD] 40 ± 14 years, VO2peak 29.9 ± 7.1 mL/kg/min) performed a maximal incremental cycling test for VO2peak determination. Genomic DNA was extracted from peripheral whole blood, and genotyping analysis was performed on 125 gene variants. Using age, sex, and body mass as covariates, and setting a stringent threshold p-value of 0.0004, only one single nucleotide polymorphism (SNP), located in the gene encoding angiotensin-converting enzyme (rs4295), was associated with VO2peak (β = 0.87; p < 2.9 × 10−4). Stepwise multiple regression analysis identified a panel of three SNPs (rs4295 = 1.1%, angiotensin II receptor type 1 rs275652 = 0.6%, and myostatin rs7570532 = 0.5%) that together accounted for 2.2% (p = 0.0007) of the interindividual variance in VO2peak. Participants carrying six ‘favorable’ alleles had a higher VO2peak (32.3 ± 8.1 mL/kg/min) than those carrying only one favorable allele (24.6 ± 5.2 mL/kg/min, p < 0.0001). In summary, VO2peak at the pre-trained state is partly influenced by several polymorphic variations in candidate genes, but they represent a minor portion of the variance.
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Reduced exercise capacity and impaired physical performance are observed in nearly all patients with liver cirrhosis. Physical activity and exercise are physiological anabolic stimuli that can reverse dysregulated protein homeostasis or proteostasis and potentially increase muscle mass and contractile function in healthy subjects. Cirrhosis is a state of anabolic resistance and unlike the beneficial responses to exercise reported in physiological states, there are few systematic studies evaluating the response to exercise in cirrhosis. Hyperammonemia is a mediator of the liver-muscle axis with net skeletal muscle ammonia uptake in cirrhosis causing signaling perturbations, mitochondrial dysfunction with decreased ATP content, modifications of contractile proteins and impaired ribosomal function, all of which contribute to anabolic resistance in cirrhosis and have the potential to impair the beneficial responses to exercise. English language publications in peer reviewed journals that specifically evaluated the impact of exercise in cirrhosis were reviewed. Most studies evaluated responses to endurance exercise and readouts included peak or maximum oxygen utilization, grip strength, and functional capacity. Endurance exercise for up to 12 weeks is clinically tolerated in well-compensated cirrhosis. Data on the safety of resistance exercise is conflicting. Nutritional supplements enhance the benefits of exercise in healthy subjects but have not been evaluated in cirrhosis. Whether the beneficial physiological responses with endurance exercise and increase in muscle mass with resistance exercise that occur in healthy subjects also occur in cirrhotics is not known. Specific organ-system responses, changes in body composition, or improved long-term clinical outcomes with exercise in cirrhosis need evaluation.
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Background International evidence-based guidelines recommend physical exercise to form part of standard care for all cancer survivors. However, at present, the optimum exercise intensity is unclear. Therefore, we aimed to evaluate the effectiveness of a high intensity (HI) and low-to-moderate intensity (LMI) resistance and endurance exercise program compared with a wait list control (WLC) group on physical fitness and fatigue in a mixed group of cancer survivors who completed primary cancer treatment, including chemotherapy. Methods Overall, 277 cancer survivors were randomized to 12 weeks of HI exercise (n = 91), LMI exercise (n = 95), or WLC (n = 91). Both interventions were identical with respect to exercise type, duration and frequency, and only differed in intensity. Measurements were performed at baseline (4–6 weeks after primary treatment) and post-intervention. The primary outcomes were cardiorespiratory fitness (peakVO2), muscle strength (grip strength and 30-second chair-stand test), and self-reported fatigue (Multidimensional Fatigue Inventory; MFI). Secondary outcomes included health-related quality of life, physical activity, daily functioning, body composition, mood, and sleep disturbances. Multilevel linear regression analyses were performed to estimate intervention effects using an intention-to-treat principle. Results In the HI and LMI groups, 74 % and 70 % of the participants attended more than 80 % of the prescribed exercise sessions, respectively (P = 0.53). HI (β = 2.2; 95 % CI, 1.2–3.1) and LMI (β = 1.3; 95 % CI, 0.3–2.3) exercise showed significantly larger improvements in peakVO2 compared to WLC. Improvements in peakVO2 were larger for HI than LMI exercise (β = 0.9; 95 % CI, −0.1 to 1.9), but the difference was not statistically significant (P = 0.08). No intervention effects were found for grip strength and the 30-second chair-stand test. HI and LMI exercise significantly reduced general and physical fatigue and reduced activity (MFI subscales) compared to WLC, with no significant differences between both interventions. Finally, compared to WLC, we found benefits in global quality of life and anxiety after HI exercise, improved physical functioning after HI and LMI exercise, and less problems at work after LMI exercise. Conclusions Shortly after completion of cancer treatment, both HI and LMI exercise were safe and effective. There may be a dose–response relationship between exercise intensity and peakVO2, favoring HI exercise. HI and LMI exercise were equally effective in reducing general and physical fatigue. Trial registration This study was registered at the Netherlands Trial Register [NTR2153] on the 5th of January 2010.
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Muscle atrophy is an unfortunate effect of aging and many diseases and can compromise physical function and impair vital metabolic processes. Low levels of muscular fitness together with insufficient dietary intake are major risk factors for illness and mortality from all causes. Ultimately, muscle wasting contributes significantly to weakness, disability, increased hospitalization, immobility, and loss of independence. However, the extent of muscle wasting differs greatly between individuals due to differences in the aging process per se as well as physical activity levels. Interventions for sarcopenia include exercise and nutrition because both have a positive impact on protein anabolism but also enhance other aspects that contribute to well-being in sarcopenic older adults, such as physical function, quality of life, and anti-inflammatory state. The process of aging is accompanied by chronic immune activation, and sarcopenia may represent a consequence of a counter-regulatory strategy of the immune system. Thereby, the kynurenine pathway is induced, and elevation in the ratio of kynurenine to tryptophan concentrations, which estimates the tryptophan breakdown rate, is often linked with inflammatory conditions and neuropsychiatric symptoms. A combined exercise program consisting of both resistance-type and endurance-type exercise may best help to ameliorate the loss of skeletal muscle mass and function, to prevent muscle aging comorbidities, and to improve physical performance and quality of life. In addition, the use of dietary protein supplementation can further augment protein anabolism but can also contribute to a more active lifestyle, thereby supporting well-being and active aging in the older population.
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Background: Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited. The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass. Methods: Eighty-one COPD patients with low muscle mass, admitted to out-patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega-3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training. Results: The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention-to-treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (-18%,P = 0.005). Conclusions: High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.
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Background: Age-related differences concerning cardiorespiratory responses and myocardial function during exercise have not been extensively investigated in healthy populations. Aims: To compare cardiorespiratory performance and myocardial function during maximal exercise in healthy/unmedicated men (older, n = 24, 63-75 years; young, n = 22, 19-25 years) and women (older, n = 18, age = 63-74 years; young, n = 23, 19-25 years). Methods: Oxygen uptake (VO2), ventilation minute (V E), heart rate (HR), stroke volume (SV), cardiac output (Q), O2 pulse (O2p), preejection period (PEP), and left ventricular ejection time (LVET) were assessed during cycle incremental exercise. Results: HR and SV remained equivalent between age groups until 75 and 50% peak workload, respectively. Q increased by 2.5 and 4.5 times in older and young groups, respectively. However, Q/VO2 ratio was always similar across age and sex groups (∼0.50). The energetic efficiency ratio (W/VO2) was also alike in older and young men, but slightly lower in women. At maximal exercise, cardiorespiratory responses were lower in older than young men and women: VO2 (-40 to 50%), V E (-35 to 37%), HR (-23%), SV (-26 to 29%), Q (-43 to 45%), and O2p (-15 to 20%). Cardiac and SV indices were lower in older than young groups by approximately 42 and 25%, respectively. LVET was longer in the older individuals, while PEP was similar across age groups. Hence, PEP/LVET was lowered among older vs. young men and women. Conclusion: Submaximal work capacity was preserved in healthy and unmedicated older individuals. Age-related lessening of maximal performance in both sexes was due to poor chronotropic and, particularly, inotropic properties of the heart.
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The prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently needed. Resistance training (RT) promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport and mitochondrial oxidative capacity. In particular, mitochondrial adaptations triggered by RT provide evidence for this type of exercise as a feasible lifestyle recommendation to combat T2D, a disease typically characterized by altered muscle mitochondrial function. Recently, the synergistic and antagonistic effects of combined training and Metformin use have come into question and warrant more in-depth prospective investigations. In the future, clinical intervention studies should elucidate the mechanisms driving RT-mitigated mitochondrial adaptations in muscle and their link to improvements in glycemic control, cholesterol metabolism and other cardiovascular disease risk factors in individuals with T2D.
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Background Reduced muscular strength in the old age is strongly related to activity impairment and mortality. However, studies evaluating the gender-specific association between muscularity and mortality among older adults are lacking. Thus, the objective of the present study was to examine gender differences in the association between muscular strength and mortality in a prospective population-based cohort study. Methods Data used in this study derived from the Cooperative Health Research in the Region of Augsburg (KORA)-Age Study. The present analysis includes 1,066 individuals (mean age 76 ± 11 SD years) followed up over 3 years. Handgrip strength was measured using the Jamar Dynamometer. A Cox proportional hazard model was used to determine adjusted hazard ratios of mortality with 95% confidence intervals (95% CI) for handgrip strength. Potential confounders (i.e. age, nutritional status, number of prescribed drugs, diseases and level of physical activity) were pre-selected according to evidence-based information. ResultsDuring the follow-up period, 56 men (11%) and 39 women (7%) died. Age-adjusted mortality rates per 1,000 person years (95% CI) were 77 (59–106), 24 (13–41) and 14 (7–30) for men and 57 (39–81), 14 (7–27) and 1 (0–19) for women for the first, second and third sex-specific tertile of muscular strength, respectively. Low handgrip strength was significantly associated with all-cause mortality among older men and women from the general population after controlling for significant confounders. Hazard ratios (95% CI) comparing the first and second tertile to the third tertle were 3.33 (1.53–7.22) and 1.42 (0.61-3.28), respectively. Respective hazard ratios (95% CI) for mortality were higher in women than in men ((5.23 (0.67–40.91) and 2.17 (0.27–17.68) versus 2.36 (0.97–5.75) and 0.97 (0.36–2.57)). Conclusions Grip strength is inversely associated with mortality risk in older adults, and this association is independent of age, nutritional status, number of prescribed drugs, number of chronic diseases and level of physical activity. The association between muscular strength and all-cause mortality tended to be stronger in women. It seems to be particularly important for the weakest to enhance their levels of muscular strength in order to reduce the risk of dying early.
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Background: Impairment in aerobic fitness is a potential modifiable risk factor for postoperative complications. In this randomized controlled trial, we hypothesized that a high-intensity interval training (HIIT) program enhances cardiorespiratory fitness before lung cancer surgery and therefore reduces the risk of postoperative complications. Methods: Patients with operable lung cancer were randomly assigned to usual care (UC, N=77) or preoperative rehabilitation based on HIIT (Rehab, N=74). Maximal cardiopulmonary exercise testing and the six-minute walk test were performed twice before surgery. The primary outcome measure was a composite of death and in-hospital postoperative complications. Results: Groups were well balanced in terms of patient characteristics. During the preoperative waiting period (median 25 days), the peak oxygen consumption (peakVO2) and the six-minute walking distance increased (respectively, median +15 % [IQ 25-75%, +9 to +22%] P=0.003 and +15% [IQ25-75, +8 to +28%], P<0.001) in the Rehab group whereas VO2peak declined in the UC group (median -8% [IQ25-75, -16 to 0%], P=0.005). The primary endpoint did not differ significantly between the two groups: 27 of the 74 patients (35.5%) in the Rehab group and 39 of 77 patients (50.6%) in the UC group developed at least one postoperative complication (P=0.080). Noteworthy, the incidence of pulmonary complications was lower in the Rehab compared with the UC group (23% vs 44%, P=0.018), owing to a significant reduction in atelectasis (12.2% vs 36.4%, P<0.001) and this was accompanied by a shorter length of stay in the postanesthesia care unit (median -7 hours, IQ25-75% -4 to -10). Conclusions: In this RCT, preoperative HIIT resulted in significant improvement in aerobic performances but failed to reduce early complications after lung cancer resection.
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Background: Considerable debate continues to surround the concept of mitochondrial dysfunction in aging muscle. We tested the overall hypothesis that age per se does not influence mitochondrial function and markers of mitochondria quality control, that is, expression of fusion, fission, and autophagy proteins. We also investigated the influence of cardiorespiratory fitness (VO2max) and adiposity (body mass index) on these associations. Methods: Percutaneous biopsies of the vastus lateralis were obtained from sedentary young (n = 14, 24±3 years), middle-aged (n = 24, 41±9 years) and older adults (n = 20, 78±5 years). A physically active group of young adults (n = 10, 27±5 years) was studied as a control. Mitochondrial respiration was determined in saponin permeabilized fiber bundles. Fusion, fission and autophagy protein expression was determined by Western blot. Cardiorespiratory fitness was determined by a graded exercise test. Results: Mitochondrial respiratory capacity and expression of fusion (OPA1 and MFN2) and fission (FIS1) proteins were not different among sedentary groups despite a wide age range (21 to 88 years). Mitochondrial respiratory capacity and fusion and fission proteins were, however, negatively associated with body mass index, and mitochondrial respiratory capacity was positively associated with cardiorespiratory fitness. The young active group had higher respiration, complex I and II respiratory control ratios, and expression of fusion and fission proteins. Finally, the expression of fusion, fission, and autophagy proteins were linked with mitochondrial respiration. Conclusions: Mitochondrial respiration and markers of mitochondrial dynamics (fusion and fission) are not associated with chronological age per se, but rather are more strongly associated with body mass index and cardiorespiratory fitness.
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Purpose Following colorectal cancer diagnosis and anti-cancer therapy, declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality. There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes. This study compared 4 weeks of moderate-intensity exercise (MIE) and high-intensity exercise (HIE) training on peak oxygen consumption (V̇O2peak) and body composition in colorectal cancer survivors. Methods Forty seven post-treatment colorectal cancer survivors (HIE = 27 months post-treatment; MIE = 38 months post-treatment) were randomised to either HIE [85–95 % peak heart rate (HRpeak)] or MIE (70 % HRpeak) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks. Results HIE was superior to MIE in improving absolute (p = 0.016) and relative (p = 0.021) V̇O2peak. Absolute (+0.28 L.min−1, p < 0.001) and relative (+3.5 ml.kg−1.min−1, p < 0.001) V̇O2 peak were increased in the HIE group but not the MIE group following training. HIE led to significant increases in lean mass (+0.72 kg, p = 0.002) and decreases in fat mass (−0.74 kg, p < 0.001) and fat percentage (−1.0 %, p < 0.001), whereas no changes were observed for the MIE group. There were no severe adverse events. Conclusions In response to short-term training, HIE is a safe, feasible and efficacious intervention that offers clinically meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors. Implications for Cancer Survivors HIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment.
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Purpose: The aim of this work was to investigate cardiorespiratory fitness in breast cancer patients at different time points of anti-cancer treatment. Patients and methods: Non-metastatic breast cancer patients (n = 222, mean age 55 years) were categorized into four subgroups according to their treatment status. Cardiopulmonary exercise testing (CPET) was used to measure patients' cardiorespiratory fitness, including oxygen delivery and metabolic muscle function. Testing was performed by bicycle ergometry, and maximal oxygen uptake (VO2peak) was measured. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of the O2 supply to muscle. Analysis of covariance was used to estimate the impact of different cancer treatments on cardiorespiratory fitness with adjustment for clinical factors. Results: Submaximal measures were successfully assessed in 220 (99%) and 200 (90%) patients for HR50 and VT, while criteria for maximal exercise testing were met by 176 patients (79%), respectively. The mean VO2peak was 20.6 ± 6.7 ml/kg/min, mean VT 10.7 ± 2.9 ml/min/kg and mean HR50 112 ± 16 beats/min. Chemotherapy was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant chemotherapy compared to patients with no chemotherapy or those who just started chemotherapy regime (all p < 0.01). Patients post adjuvant chemotherapy reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5 ± 4.8 ml/kg/min). Similarly, HR50 was significantly associated with treatment. However, VT was not associated with treatment. Conclusion: Breast cancer patients have marked and significantly impaired cardiopulmonary function during and after chemotherapy. Hereby, chemotherapy appears to impair cardiorespiratory fitness by influencing the oxygen delivery system rather than impacting metabolic muscle function. Our findings underline the need of exercise training in breast cancer patients to counteract the loss of cardiorespiratory fitness during the anti-cancer treatment.
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Muscle wasting and cachexia are the ultimate consequence of aging and a variety of acute and chronic illnesses. Significant efforts are made by many stakeholders to develop effective therapies. An important aspect of successful therapeutic development research is a common nomenclature for effective communication between researchers and clinicians, to the public, and also with regulatory bodies. Despite several efforts to develop consensus definitions for cachexia and sarcopenia, including such new terms for muscle wasting as myopenia, a common conceptual approach and acceptable vocabulary and classification system are yet to be established. Notwithstanding the potential need to translate such disease definitions and terminologies into different languages, we advocate the use of the term "muscle wasting" as the unifying entity that represents the single most common disease process across a large spectrum of cachexia and in sarcopenia-associated disorders. In this paper, we outline a first proposal for the disease nomenclature and classification of "Muscle Wasting Diseases." This concept can be applied in acute and chronic disease settings. It is pertinent for wasting diseases, cachexia, and sarcopenia of any severity and due to any underlying illness. The concept of muscle wasting disease underscores the most common denominator of the underlying wasting processes, i.e., muscle wasting, without ignoring the advanced disease states that are also accompanied by fat tissue wasting. The term muscle wasting disease is easily understood by both the scientific community and the lay public. This may promote its general use and efforts to heighten education and awareness in the field.
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To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer. Meta-analysis of randomised controlled trials with data extraction and quality assessment performed independently by two researchers. Pubmed, CINAHL, and Google Scholar from the earliest possible year to September 2011. References from meta-analyses and reviews. Randomised controlled trials that assessed the effects of physical activity in adults who had completed their main cancer treatment, except hormonal treatment. There were 34 randomised controlled trials, of which 22 (65%) focused on patients with breast cancer, and 48 outcomes in our meta-analysis. Twenty two studies assessed aerobic exercise, and four also included resistance or strength training. The median duration of physical activity was 13 weeks (range 3-60 weeks). Most control groups were considered sedentary or were assigned no exercise. Based on studies on patients with breast cancer, physical activity was associated with improvements in insulin-like growth factor-I, bench press, leg press, fatigue, depression, and quality of life. When we combined studies on different types of cancer, we found significant improvements in body mass index (BMI), body weight, peak oxygen consumption, peak power output, distance walked in six minutes, right handgrip strength, and quality of life. Sources of study heterogeneity included age, study quality, study size, and type and duration of physical activity. Publication bias did not alter our conclusions. Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, and quality of life in patients after treatment for breast cancer. When patients with cancer other than breast cancer were also included, physical activity was associated with reduced BMI and body weight, increased peak oxygen consumption and peak power output, and improved quality of life.
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The purpose of this Position Stand is to provide guidance to professionals who counsel and prescribe individualized exercise to apparently healthy adults of all ages. These recommendations also may apply to adults with certain chronic diseases or disabilities, when appropriately evaluated and advised by a health professional. This document supersedes the 1998 American College of Sports Medicine (ACSM) Position Stand, "The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness, and Flexibility in Healthy Adults." The scientific evidence demonstrating the beneficial effects of exercise is indisputable, and the benefits of exercise far outweigh the risks in most adults. A program of regular exercise that includes cardiorespiratory, resistance, flexibility, and neuromotor exercise training beyond activities of daily living to improve and maintain physical fitness and health is essential for most adults. The ACSM recommends that most adults engage in moderate-intensity cardiorespiratory exercise training for ≥30 min·d on ≥5 d·wk for a total of ≥150 min·wk, vigorous-intensity cardiorespiratory exercise training for ≥20 min·d on ≥3 d·wk (≥75 min·wk), or a combination of moderate- and vigorous-intensity exercise to achieve a total energy expenditure of ≥500-1000 MET·min·wk. On 2-3 d·wk, adults should also perform resistance exercises for each of the major muscle groups, and neuromotor exercise involving balance, agility, and coordination. Crucial to maintaining joint range of movement, completing a series of flexibility exercises for each the major muscle-tendon groups (a total of 60 s per exercise) on ≥2 d·wk is recommended. The exercise program should be modified according to an individual's habitual physical activity, physical function, health status, exercise responses, and stated goals. Adults who are unable or unwilling to meet the exercise targets outlined here still can benefit from engaging in amounts of exercise less than recommended. In addition to exercising regularly, there are health benefits in concurrently reducing total time engaged in sedentary pursuits and also by interspersing frequent, short bouts of standing and physical activity between periods of sedentary activity, even in physically active adults. Behaviorally based exercise interventions, the use of behavior change strategies, supervision by an experienced fitness instructor, and exercise that is pleasant and enjoyable can improve adoption and adherence to prescribed exercise programs. Educating adults about and screening for signs and symptoms of CHD and gradual progression of exercise intensity and volume may reduce the risks of exercise. Consultations with a medical professional and diagnostic exercise testing for CHD are useful when clinically indicated but are not recommended for universal screening to enhance the safety of exercise.
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Background: Aging is associated with loss in both muscle mass and the metabolic quality of skeletal muscle. A major part of these changes is associated with an age-related decrease in the level of physical activity and may be counteracted by endurance training (ET) and resistance training (RT). Objective: Since both muscle strength and aerobic power decrease with age, we investigated what form of training might be best for improvements in physical performance in the elderly. In detail, we wanted to know whether systematic ET can augment muscle strength and/or whether systematic RT can augment the aerobic power of healthy elderly adults. Methods: Forty-two volunteers (32 women, 10 men) were recruited for the study and randomized into three groups: 13 persons undertook a continuous 6-month ET program, 15 undertook a continuous 6-month RT program and 14 served as a control group. All persons performed a cycling test to measure aerobic power (VO(2max)) and maximum workload (W(max)) before and after the training period. Maximum strength was determined from one repetition maximum (1-RM). Results: After 6 months of RT, maximum strength increased by an average of 15% for leg press (P < 0.01), 25% for bench press (P < 0.01) and 30% for bench pull (P < 0.001); ET showed no effect on maximum strength except for the 1-RM in bench pull. Aerobic power improved by 6% in the ET group and by 2.5% in the RT group, neither of which was significant. Maximum workload improved significantly by 31% in the ET group (P < 0.001) and by 6% in the RT group (P = 0.05). ET resulted in a significant 5.3% reduction of body fat (P < 0.05), whereas only RT increased lean body mass by 1.0 +/- 0.5 kg. Conclusion: RT leads to a genuine increase in lean body mass and muscle strength in healthy elderly adults and is therefore the best method for treatment of amyotrophia. ET appears to be the most efficacious training mode for maintaining and improving maximum aerobic power in the elderly and should be viewed as a complement to RT. The loading intensity to promote hypertrophy should approach 60-80% of 1-RM with an exercise volume ranging from 3 to 6 sets per muscle group per week of 10-15 repetitions per exercise. ET should be performed on two days per week controlled by a heart rate according to 60% of VO(2max) and an exercise volume ranging from 30 to 60 minutes per week.
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This study examined the effects of short-term endurance training (ET) on the left ventricular (LV