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Dose response curve of MPS in elderly and young muscle with protein ingestion at rest. MPS in the young is stimulated above basal with ~2.5 g of crystalline EAA (found in ~5 g of intact protein) before reaching a plateau at ~10 g of crystalline EAA (found in ~20 g of intact protein). In the elderly, MPS is increased above rest after ingestion of 20 g of whey protein and, like younger adults, the response plateaus thereafter. Star indicates MPS in both young and elderly after 6.7 g of EAA (typically found in 15 g of whey protein) enriched with leucine (41% or ~2.8 g) [36]. Finely dashed lines indicate the hypothesized leucine 'threshold' which must be surpassed in order to stimulate a robust increase in rates of MPS. The threshold may be considerably lower in the young (<1 g leucine in 2.5 g of crystalline EAA's) compared with the elderly (~1.5-2 g of leucine contained in 15-20 g of whey protein).

Dose response curve of MPS in elderly and young muscle with protein ingestion at rest. MPS in the young is stimulated above basal with ~2.5 g of crystalline EAA (found in ~5 g of intact protein) before reaching a plateau at ~10 g of crystalline EAA (found in ~20 g of intact protein). In the elderly, MPS is increased above rest after ingestion of 20 g of whey protein and, like younger adults, the response plateaus thereafter. Star indicates MPS in both young and elderly after 6.7 g of EAA (typically found in 15 g of whey protein) enriched with leucine (41% or ~2.8 g) [36]. Finely dashed lines indicate the hypothesized leucine 'threshold' which must be surpassed in order to stimulate a robust increase in rates of MPS. The threshold may be considerably lower in the young (<1 g leucine in 2.5 g of crystalline EAA's) compared with the elderly (~1.5-2 g of leucine contained in 15-20 g of whey protein).

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ABSTRACT: Age-related muscle wasting (sarcopenia) is accompanied by a loss of strength which can compromise the functional abilities of the elderly. Muscle proteins are in a dynamic equilibrium between their respective rates of synthesis and breakdown. It has been suggested that age-related sarcopenia is due to: i) elevated basal-fasted rates of mu...

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... In these acute feeding studies using a randomized, cross-over design, the initial "proof of concept" was developed to hypothesize the physiological outcomes described herein. The profile of EAAs in EMR was formulated to optimize translation of protein synthesis and overcome anabolic resistance in the context of aging without a concomitant increase in calories [18]. Therefore, the daily provision of EMR over the course of 4 weeks provided the requisite nutrientinduced stimulus to promote thigh skeletal muscle accretion in obese older individuals. ...
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... To slow muscle mass loss, resistance exercise is often employed; however, gains in muscle mass are blunted following resistance exercise of aged individuals when compared to younger adults, a phenomenon known as anabolic resistance [3]. Various mechanisms, such as dysregulated growth signaling [4,5], altered protein anabolism and catabolism [6], defective autophagy [7], and reduced mitochondrial function [8], have been shown to contribute to anabolic resistance; however, our recent work suggests that an accumulation of senescent cells during muscle remodeling could be a contributing factor [9]. Senescent cells secrete a host of biomolecules including pro-inflammatory cytokines, growth factors, and proteases known as the senescent-associated secretory phenotype (SASP) [10,11]. The SASP can blunt mTORC1-mediated growth signaling [12], elevate protein catabolism [13], and dysregulate cytoskeletal remodeling [14], which may result in blunted muscle growth and contribute to anabolic resistance in aged muscle. ...
... Many older adults suffer from a diminished ability to grow skeletal muscle with resistance training, termed anabolic resistance, which may be due to a host of defective biologic processes [4,6,63]. Unfortunately, there has been limited success in developing therapeutic interventions to augment gains in muscle mass in these individuals. ...
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With aging, skeletal muscle plasticity is attenuated in response to exercise. Here, we report that senescent cells, identified using senescence-associated β-galactosidase (SA β-Gal) activity and p21 immunohistochemistry, are very infrequent in resting muscle, but emerge approximately 2 weeks after a bout of resistance exercise in humans. We hypothesized that these cells contribute to blunted hypertrophic potential in old age. Using synergist ablation-induced mechanical overload (MOV) of the plantaris muscle to model resistance training in adult (5-6-month) and old (23-24-month) male C57BL/6 J mice, we found increased senescent cells in both age groups during hypertrophy. Consistent with the human data, there were negligible senescent cells in plantaris muscle from adult and old sham controls, but old mice had significantly more senescent cells 7 and 14 days following MOV relative to young. Old mice had blunted whole-muscle hypertrophy when compared to adult mice, along with smaller muscle fibers, specifically glycolytic type 2x + 2b fibers. To ablate senescent cells using a hit-and-run approach, old mice were treated with vehicle or a senolytic cocktail consisting of 5 mg/kg dasatinib and 50 mg/kg quercetin (D + Q) on days 7 and 10 during 14 days of MOV; control mice underwent sham surgery with or without senolytic treatment. Old mice given D + Q had larger muscles and muscle fibers after 14 days of MOV, fewer senescent cells when compared to vehicle-treated old mice, and changes in the expression of genes (i.e., Igf1, Ddit4, Mmp14) that are associated with hypertrophic growth. Our data collectively show that senescent cells emerge in human and mouse skeletal muscle following a hypertrophic stimulus and that D + Q improves muscle growth in old mice.
... It has been postulated that these discrepancies are related to methodological nuances in measuring protein metabolism, including pre-study sedentarism and controlling habitual diets, the timing of samples, and the isotopic method employed [63]. Additionally, while chronological age is important, it may be less important than the ability to distinguish between pre-frail, frail, and healthy older adults, which may also impact protein turnover [64]. ...
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... However, we did not find significant associations between ω-3 and muscle mass when young and middle-aged individuals were evaluated. The lack of association in young individuals can possibly be explained because these individuals likely present normal muscle protein synthesis [21]; therefore, the effect of ω-3 in enhancing the protein synthesis may not be relevant. In addition, since middle-aged individuals are at the beginning of the muscle mass loss and anabolic resistance [26], it is possible to suggest that plasma ω-3 may not have an effect to improve the protein synthesis in this age-range. ...
... Since inflammation is one of the causes of muscle wasting [21,22], individuals ingesting higher amounts of ω-3 can have reduced pro-inflammatory cytokines [15] preserving muscle mass [28]. However, no association was observed in the present study, even when men and women were evaluated separately. ...
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The aim of this study was to evaluate the association between plasma ω-3 and appendicular muscle mass index (AMMI) in young and middle-aged individuals and also to evaluate whether these associations are sex-specific. A cross-sectional study was performed evaluating 1037 individuals aged 20 to 59 years from a sub-sample of the National Health and Nutrition Examination Survey (NHANES) 2011-2012 Plasma ω-3 was evaluated by gas chromatography-mass spectrometry and lean mass was assessed by dual-energy x-ray absorptiometry (DXA). Total plasma ω-3, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and alpha-linolenic acid (ALA) were not associated with AMMI in total sample, men and women after adjustments for confounders. Plasma ω-3 and its subtypes were not associated with AMMI in a sub analysis evaluating young (20 to 44 y) and middle-aged (45 to 59 y) individuals separately. In conclusion, plasma ω-3 fatty acids are not associated with AMMI in young and middle-aged individuals regardless of sex.