RESUMO
Mechanisms underlying mechanical overload-induced skeletal muscle hypertrophy have been extensively researched since the landmark report by Morpurgo (1897) of "work-induced hypertrophy" in dogs that were treadmill trained. Much of the preclinical rodent and human resistance training research to date supports that involved mechanisms include enhanced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, an expansion in translational capacity through ribosome biogenesis, increased satellite cell abundance and myonuclear accretion, and postexercise elevations in muscle protein synthesis rates. However, several lines of past and emerging evidence suggest that additional mechanisms that feed into or are independent of these processes are also involved. This review first provides a historical account of how mechanistic research into skeletal muscle hypertrophy has progressed. A comprehensive list of mechanisms associated with skeletal muscle hypertrophy is then outlined, and areas of disagreement involving these mechanisms are presented. Finally, future research directions involving many of the discussed mechanisms are proposed.
Assuntos
Músculo Esquelético , Transdução de Sinais , Humanos , Animais , Cães , Músculo Esquelético/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Biossíntese de Proteínas , Hipertrofia/metabolismo , Mamíferos/metabolismoRESUMO
Aerobic and resistance exercise (RE) induce distinct molecular responses. One hypothesis is that these responses are antagonistic and unfavorable for the anabolic response to RE when concurrent exercise is performed. This thesis may also depend on the participants' training status and concurrent exercise order. We measured free-living myofibrillar protein synthesis (MyoPS) rates and associated molecular responses to resistance-only and concurrent exercise (with different exercise orders), before and after training. Moderately active men completed one of three exercise interventions (matched for age, baseline strength, body composition, and aerobic capacity): resistance-only exercise (RE, n = 8), RE plus high-intensity interval exercise (RE+HIIE, n = 8), or HIIE+RE (n = 9). Participants trained 3 days/week for 10 weeks; concurrent sessions were separated by 3 h. On the first day of Weeks 1 and 10, muscle was sampled immediately before and after, and 3 h after each exercise mode and analyzed for molecular markers of MyoPS and muscle glycogen. Additional muscle, sampled pre- and post-training, was used to determine MyoPS using orally administered deuterium oxide (D2 O). In both weeks, MyoPS rates were comparable between groups. Post-exercise changes in proteins reflective of protein synthesis were also similar between groups, though MuRF1 and MAFbx mRNA exhibited some exercise order-dependent responses. In Week 10, exercise-induced changes in MyoPS and some genes (PGC-1É and MuRF1) were dampened from Week 1. Concurrent exercise (in either order) did not compromise the anabolic response to resistance-only exercise, before or after training. MyoPS rates and some molecular responses to exercise are diminished after training.
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Composição Corporal , Exercício Físico , Masculino , Humanos , Tolerância ao Exercício , Glicogênio , MúsculosRESUMO
In this issue, Burke et al. discuss the utility of the rodent synergist ablation (SA) model for examining mechanisms associated with skeletal muscle hypertrophy. In this invited perspective, we aim to complement their original perspective by discussing limitations to the model along with alternative mechanical overload models that have strengths and limitations.
Assuntos
Hipertrofia , Músculo Esquelético , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Modelos Animais de Doenças , Técnicas de Ablação/métodos , Ratos , Camundongos , RoedoresRESUMO
Ribosomes are essential cellular machinery for protein synthesis. It is hypothesised that ribosome content supports muscle growth and that individuals with more ribosomes have greater increases in muscle size following resistance training (RT). Aerobic conditioning (AC) also elicits distinct physiological adaptations; however, no measures of ribosome content following AC have been conducted. We used ribosome-related gene expression as a proxy measure for ribosome content and hypothesised that AC and RT would increase ribosome-related gene expression. Fourteen young men and women performed 6 weeks of single-legged AC followed by 10 weeks of double-legged RT. Muscle biopsies were taken following AC and following RT in the aerobically conditioned (AC+RT) and unconditioned (RT) legs. No differences in regulatory genes (Ubf, Cyclin D1, Tif-1a and Polr-1b) involved in ribosomal biogenesis or ribosomal RNA (45S, 5.8S, 18S and 28S rRNAs) expression were observed following AC and RT, except for c-Myc (RT > AC+RT) and 5S rRNA (RT < AC+RT at pre-RT) with 18S external transcribed spacer and 5.8S internal transcribed spacer expression decreasing from pre-RT to post-RT in the RT leg only. When divided for change in leg-lean soft tissue mass (ΔLLSTM) following RT, legs with the greatest ΔLLSTM had lower expression in 11/13 measured ribosome-related genes before RT and decreased expression in 9/13 genes following RT. These results indicate that AC and RT did not increase ribosome-related gene expression. Contrary to previous research, the greatest increase in muscle mass was associated with lower changes in ribosome-related gene expression over the course of the 10-week training programme. This may point to the importance of translational efficiency rather than translational capacity (i.e. ribosome content) in mediating long-term exercise-induced adaptations in skeletal muscle.
Assuntos
Músculo Esquelético , Treinamento Resistido , Ribossomos , Feminino , Humanos , Masculino , Regulação da Expressão Gênica , Hipertrofia/genética , Hipertrofia/metabolismo , Músculo Esquelético/metabolismo , Biossíntese de Proteínas/genética , Ribossomos/genética , Adulto JovemRESUMO
The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due to the presence of 'anabolic resistance', resulting in muscle loss. Sarcopenia can be transiently but markedly accelerated through periods of muscle disuse-induced (i.e., unloading) atrophy due to reduced physical activity, sickness, immobilisation or hospitalisation. Periods of disuse are detrimental to older adults' overall quality of life and substantially increase their risk of falls, physical and social dependence, and early mortality. Disuse events induce skeletal muscle atrophy through various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis and mitochondrial dysfunction, all of which tip the scales in favour of a negative net protein balance and subsequent muscle loss. Concerningly, recovery from disuse atrophy is more difficult for older adults than their younger counterparts. Resistance training (RT) is a potent anabolic stimulus that can robustly stimulate muscle protein synthesis and mitigate muscle losses in older adults when implemented before, during and following unloading. RT may take the form of traditional weightlifting-focused RT, bodyweight training and lower- and higher-load RT. When combined with sufficient dietary protein, RT can accelerate older adults' recovery from a disuse event, mitigate frailty and improve mobility; however, few older adults regularly participate in RT. A feasible and practical approach to improving the accessibility and acceptability of RT is through the use of resistance bands. Moving forward, RT must be prescribed to older adults to mitigate the negative consequences of disuse atrophy.
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The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.
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Medicina Esportiva , Esportes , Feminino , Humanos , Masculino , Identidade de Gênero , Atletas , TestosteronaRESUMO
This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance profile or turnover rate of proteins in this population. Men with (n = 3) or without (n = 4) obesity were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D2 O) consumption and serial biopsies of vastus lateralis muscle. Men with obesity then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100% maximum aerobic power interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. Proteomic analysis detected 352 differences (p < 0.05, false discovery rate < 5%) in protein abundance and 19 (p < 0.05) differences in protein turnover, including components of the ubiquitin-proteasome system. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p < 0.05) and tended to benefit proteostasis by increasing muscle protein turnover rates. Obesity and insulin resistance are associated with compromised muscle proteostasis, which may be partially restored by endurance exercise.
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Low energy availability (LEA) describes a state where the energy intake is insufficient to cover the energy costs of both exercise energy expenditure and basal physiological body functions. LEA has been associated with various physiological consequences, such as reproductive dysfunction. However, the effect of LEA on skeletal muscle protein synthesis in females performing exercise training is still poorly understood. We conducted a randomized controlled trial to investigate the impact of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in trained females. Thirty eumenorrheic females were matched based on training history and randomized to undergo 10 days of LEA (25 kcal · kg fat-free mass (FFM)-1 · day-1 ) or optimal energy availability (OEA, 50 kcal · kg FFM-1 · day-1 ). Before the intervention, both groups underwent a 5-day 'run-in' period with OEA. All foods were provided throughout the experimental period with a protein content of 2.2 g kg lean mass-1 · day-1 . A standardized, supervised combined resistance and cardiovascular exercise training programme was performed over the experimental period. Daily integrated muscle protein synthesis was measured by deuterium oxide (D2 O) consumption along with changes in body composition, resting metabolic rate, blood biomarkers and 24 h nitrogen balance. We found that LEA reduced daily integrated myofibrillar and sarcoplasmic muscle protein synthesis compared with OEA. Concomitant reductions were observed in lean mass, urinary nitrogen balance, free androgen index, thyroid hormone concentrations and resting metabolic rate following LEA. These results highlight that LEA may negatively affect skeletal muscle adaptations in females performing exercise training. KEY POINTS: Low energy availability (LEA) with potential health and performance impairments is widespread among female athletes. We investigated the impact of 10 days of LEA on daily integrated myofibrillar and sarcoplasmic muscle protein synthesis in young, trained females. We show that LEA impairs myofibrillar and sarcoplasmic muscle protein synthesis in trained females performing exercise training. These findings suggest that LEA may have negative consequences for skeletal muscle adaptations and highlight the importance of ensuring adequate energy availability in female athletes.
Assuntos
Metabolismo Energético , Proteínas Musculares , Humanos , Feminino , Proteínas Musculares/metabolismo , Metabolismo Energético/fisiologia , Ingestão de Energia , Músculo Esquelético/metabolismo , Nitrogênio/metabolismoRESUMO
PURPOSE OF REVIEW: Very low-calorie diets (VLCD) are used as a weight loss intervention, but concerns have been raised about their potential negative impact on lean mass. Here, we review the available evidence regarding the effects of VLCD on lean mass and explore their utility and strategies to mitigate reductions in skeletal muscle. RECENT FINDINGS: We observed that VLCD, despite their effects on lean mass, may be suitable in certain populations but have a risk in reducing lean mass. The extent of the reduction in lean mass may depend on various factors, such as the duration and degree of energy deficit of the diet, as well as the individual's starting weight and overall health. SUMMARY: VLCD may be a viable option in certain populations; however, priority needs to be given to resistance exercise training, and secondarily to adequate protein intake should be part of this dietary regime to mitigate losing muscle mass.
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Dieta Redutora , Obesidade , Humanos , Obesidade/metabolismo , Restrição Calórica , Exercício Físico/fisiologia , Músculo Esquelético/metabolismoRESUMO
This review is a tribute to honor Dr Douglas Paddon-Jones by highlighting his career research contributions. Dr Paddon-Jones was a leader in recognizing the importance of muscle health and the interactions of physical activity and dietary protein for optimizing the health span. Aging is characterized by loss of muscle mass and strength associated with reduced rates of muscle protein synthesis (MPS) and the ability to repair and replace muscle proteins. Research from the team at the University of Texas Medical Branch in Galveston discovered that the age-related decline in MPS could be overcome by increasing the quantity or quality of dietary protein at each meal. Dr Paddon-Jones was instrumental in proposing and testing a "protein threshold" of â¼30 g protein/meal to optimize MPS in older adults. Dr Paddon-Jones demonstrated that physical inactivity greatly accelerates the loss of muscle mass and function in older adults. His work in physical activity led him to propose the "Catabolic Crisis Model" of muscle size and function losses, suggesting that age-related muscle loss is not a linear process, but the result of acute periods of disuse associated with injuries, illnesses, and bed rest. This model creates the opportunity to provide targeted interventions via protein supplementation and/or increased dietary protein through consuming high-quality animal-source foods. He illustrated that nutritional support, particularly enhanced protein quantity, quality, and meal distribution, can help preserve muscle health during periods of inactivity and promote health across the life course.
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Promoção da Saúde , Músculo Esquelético , Animais , Masculino , Proteínas Alimentares/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , História do Século XX , História do Século XXIRESUMO
Nutrient Profiling Systems provide frameworks to assess the healthfulness of foods based on food composition and are intended as inputs into strategies to improve diets. Many Nutrient Profiling Systems are founded on a reductionist assumption that the healthfulness of foods is determined by the sum of their individual nutrients, with no consideration for the extent and purpose of processing and its health implications. A novel Nutrient Profiling System called Food Compass attempted to address existing gaps and provide a more holistic assessment of the healthfulness of foods. We propose that the chosen algorithm is not well justified and produces results that fail to discriminate for common shortfall nutrients, exaggerate the risks associated with animal-source foods, and underestimate the risks associated with ultraprocessed foods. We caution against the use of Food Compass in its current form to inform consumer choices, policies, programs, industry reformulations, and investment decisions.
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Dieta , Alimentos , Valor Nutritivo , Nutrientes , Ração Animal , AlgoritmosRESUMO
Factors influencing inter-individual variability of responses to resistance training (RT) remain to be fully elucidated. We have proposed the importance of capillarization in skeletal muscle for the satellite cell (SC) response to RT-induced muscle hypertrophy, and hypothesized that aerobic conditioning (AC) would augment RT-induced adaptations. Fourteen healthy young (22 ± 2 years) men and women underwent AC via 6 weeks of unilateral cycling followed by 10 weeks of bilateral RT to investigate how AC alters SC content, activity, and muscle hypertrophy following RT. Muscle biopsies were taken at baseline (unilateral), post AC (bilateral), and post RT (bilateral) in the aerobically conditioned (AC + RT) and unconditioned (RT) legs. Immunofluorescence was used to determine muscle capillarization, fiber size, SC content, and activity. Type I and type II fiber cross-sectional area (CSA) increased following RT, and when legs were analyzed independently, AC + RT increased type I, type II, and mixed-fiber CSA, where the RT leg tended to increase type II (p = .05), but not type I or mixed-fiber CSA. SC content, activation, and differentiation increased with RT, where type I total and quiescent SC content was greater in AC + RT compared to the RT leg. Those with the greatest capillary-to-fiber perimeter exchange index before RT had the greatest change in CSA following RT and a significant relationship was observed between type II fiber capillarization and the change in type II-fiber CSA with RT (r = 0.35). This study demonstrates that AC prior to RT can augment RT-induced muscle adaptions and that these differences are associated with increases in capillarization.
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Treinamento Resistido , Células Satélites de Músculo Esquelético , Capilares/patologia , Feminino , Humanos , Hipertrofia/patologia , Masculino , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologiaRESUMO
OBJECTIVE: To determine how distinct combinations of resistance training prescription (RTx) variables (load, sets and frequency) affect muscle strength and hypertrophy. DATA SOURCES: MEDLINE, Embase, Emcare, SPORTDiscus, CINAHL, and Web of Science were searched until February 2022. ELIGIBILITY CRITERIA: Randomised trials that included healthy adults, compared at least 2 predefined conditions (non-exercise control (CTRL) and 12 RTx, differentiated by load, sets and/or weekly frequency), and reported muscle strength and/or hypertrophy were included. ANALYSES: Systematic review and Bayesian network meta-analysis methodology was used to compare RTxs and CTRL. Surface under the cumulative ranking curve values were used to rank conditions. Confidence was assessed with threshold analysis. RESULTS: The strength network included 178 studies (n=5097; women=45%). The hypertrophy network included 119 studies (n=3364; women=47%). All RTxs were superior to CTRL for muscle strength and hypertrophy. Higher-load (>80% of single repetition maximum) prescriptions maximised strength gains, and all prescriptions comparably promoted muscle hypertrophy. While the calculated effects of many prescriptions were similar, higher-load, multiset, thrice-weekly training (standardised mean difference (95% credible interval); 1.60 (1.38 to 1.82) vs CTRL) was the highest-ranked RTx for strength, and higher-load, multiset, twice-weekly training (0.66 (0.47 to 0.85) vs CTRL) was the highest-ranked RTx for hypertrophy. Threshold analysis demonstrated these results were extremely robust. CONCLUSION: All RTx promoted strength and hypertrophy compared with no exercise. The highest-ranked prescriptions for strength involved higher loads, whereas the highest-ranked prescriptions for hypertrophy included multiple sets. PROSPERO REGISTRATION NUMBER: CRD42021259663 and CRD42021258902.
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Treinamento Resistido , Humanos , Adulto , Feminino , Treinamento Resistido/métodos , Teorema de Bayes , Metanálise em Rede , Músculo Esquelético/fisiologia , Força Muscular/fisiologia , Hipertrofia , PrescriçõesRESUMO
Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.
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Transtornos Musculares Atróficos , Envelhecimento , Humanos , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Transtornos Musculares Atróficos/patologiaRESUMO
Satellite cells (SCs) and ribosomes are key determinants of the skeletal muscle adaptive response. Both are thought to increase acutely after resistance exercise and chronically with resistance training. However, the acute SC and ribosome exercise response with prior aerobic conditioning is unknown. Fourteen young men and women underwent 6 wk of single-legged aerobic conditioning followed by an acute bout of 300 eccentric contractions on each leg. Muscle biopsies were taken from the vastus lateralis of the aerobically conditioned (AC) and the control (CTL) legs before (Pre), 24 (24 h), and 48 (48 h) h post-contractions. Pre-eccentric contractions, 45S pre-rRNA and 5.8S internal transcribed spacer (ITS) expression were lower in the AC leg compared with the CTL leg. SC content (PAX7+ cells/100 fibers) in type I and mixed fibers showed a main effect of condition, where values were greater in the AC leg compared with the CTL. A main effect of condition for Pax7 and MyoD1 mRNA expression was observed where expression was greater in the AC leg compared with the CTL. AC had greater RNA concentration and mRNA expression of Ubf and Tif-1a compared with CTL. Only the AC leg increased (Pre-24h) 45S pre-rRNA, 5.8S ITS, and 28S ITS following eccentric contractions. We discovered that aerobic conditioning increased type-I SC abundance and the acute increase in ribosome content following eccentric contractions.
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Músculo Esquelético , Células Satélites de Músculo Esquelético , Masculino , Humanos , Feminino , Músculo Esquelético/metabolismo , Precursores de RNA/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Ribossomos/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: The stimulation of muscle protein synthesis (MPS) by dietary protein is reduced with age. We hypothesized that twice-daily milk consumption would increase daily rates of MPS in older women relative to a nondairy milk alternative and that MPS would be enhanced by increased physical activity (PA). METHODS: Twenty-two older women were randomly assigned to 1 of 3 experimental groups: whole milk (WM; n = 7, 69 ± 3 y), skim milk (SM; n = 7, 68 ± 3 y), or an almond beverage (AB; n = 8, 63 ± 3 y). From days 1 to 3, participants consumed a standardized diet (0.8 g proteinâ kg-1 â d-1) and performed their habitual PA (Phase 1, Baseline). From days 4 to 6, participants continued to perform habitual PA, but consumed an intervention diet consisting of the standardized diet plus twice-daily beverages (250 mL each) of either WM, SM, or AB (Phase 2, Diet Intervention). Finally, from days 7 to 9, the intervention diet was consumed, and PA via daily steps was increased to â¼150% of habitual daily steps (Phase 3, Intervention Diet + PA). Deuterated water was ingested throughout the study, and muscle biopsies were taken on days 1, 4, 7, and 10 to measure MPS. RESULTS: Daily MPS rates were not differentially affected by the addition of WM, SM, or AB to a standardized diet. There was, however, a significant effect of study phase such that, when collapsed across conditions, MPS was significantly increased from Phase 1 to Phase 2 (+0.133%â d-1; 95% CI: 0.035-0.231; P < 0.01) and further increased from Phase 2 to Phase 3 (+0.156%â d-1; 95% CI: 0.063-0.250; P < 0.01). CONCLUSIONS: Increasing PA through walking was sufficient to increase daily MPS rates in older women, irrespective of whether dietary protein intake is increased beyond the recommended intake of 0.8 gâ kg-1 â d-1. The trial was registered at clinicaltrials.gov as NCT04981652.
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Proteínas Alimentares , Treinamento Resistido , Idoso , Proteínas Alimentares/metabolismo , Suplementos Nutricionais , Feminino , Humanos , Músculo Esquelético , CaminhadaRESUMO
We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.
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Hipertrofia/patologia , Íntrons , Fibras Musculares Esqueléticas/patologia , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Treinamento Resistido/efeitos adversos , Proteína Gli3 com Dedos de Zinco/genética , Adulto , Estudo de Associação Genômica Ampla , Humanos , Hipertrofia/etiologia , Hipertrofia/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Adulto JovemRESUMO
Muscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during short-term disuse in humans. After consuming a bolus dose of deuterium oxide (D2 O; 3 mL.kg-1 ), eight healthy males (22 ± 2 years) underwent 4 days of unilateral lower-limb immobilization. Bilateral muscle biopsies were obtained post-intervention for RNA sequencing and D2 O-derived measurement of MPS, with thigh lean mass quantified using dual-energy X-ray absorptiometry. Application of weighted gene co-expression network analysis identified 15 distinct gene clusters ("modules") with an expression profile regulated by disuse and/or quantitatively connected to disuse-induced muscle mass or MPS changes. Module scans for candidate targets established an experimentally tractable set of candidate regulatory molecules (242 hub genes, 31 transcriptional regulators) associated with disuse-induced maladaptation, many themselves potently tied to disuse-induced reductions in muscle mass and/or MPS and, therefore, strong physiologically relevant candidates. Notably, we implicate a putative role for muscle protein breakdown-related molecular networks in impairing MPS during short-term disuse, and further establish DEPTOR (a potent mTOR inhibitor) as a critical mechanistic candidate of disuse driven MPS suppression in humans. Overall, these findings offer a strong benchmark for accelerating mechanistic understanding of short-term muscle disuse atrophy that may help expedite development of therapeutic interventions.
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Proteínas Musculares/genética , Músculo Esquelético/fisiologia , Atrofia Muscular/genética , Doenças Musculares/genética , Biossíntese de Proteínas/genética , Transcriptoma/genética , Adulto , Humanos , Masculino , Força Muscular/genética , Adulto JovemRESUMO
OBJECTIVE: To examine the effects of community-based resistance training (RT) on physical function for older adults with mobility disability. DATA SOURCES: Four databases (PubM, PubMed, MEDLINE, Ovid, Cumulative Index to Nursing and Allied Health, Web of Science) were searched from inception to February 2, 2021. STUDY SELECTION: Randomized controlled trials that examined community-based RT for improving physical function in community-dwelling older adults were included. DATA EXTRACTION: Two reviewers independently conducted title and abstract screening, full-text evaluation, data extraction, and risk of bias quality assessment. DATA SYNTHESIS: Twenty-four studies (3656 participants; age range, 63-83 years) were included. RT programs ranged from 10 weeks to 18 months in duration. RT was more effective than control in improving 6-minute walk test distance (n=638; mean difference [MD], 16.1m; 95% CI, 12.27-19.94; P<.0001), lower extremity strength (n=785; standardized MD, 2.01; 95% CI, 1.27-2.75; P<.0001), and usual gait speed (n= 2106; MD, 0.05 m/s, 95% CI, 0.03-0.07; P<.001). In sensitivity analyses, benefits were maintained when studies with a high risk of bias were excluded. There was no effect of RT on fast gait speed or Short Physical Performance Battery score compared with control. CONCLUSIONS: RT improves walking distance, lower extremity strength, and usual gait speed in older adults with mobility disability. Improvements in physical function could increase independence in activities of daily living for this at-risk population.
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Treinamento Resistido , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Humanos , Vida Independente , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Velocidade de CaminhadaRESUMO
OBJECTIVE: To identify the efficacy of group-based nutrition interventions to increase healthy eating, reduce nutrition risk, improve nutritional status and improve physical mobility among community-dwelling older adults. DESIGN: Systematic review. Electronic databases MEDLINE, CINAHL, EMBASE, PsycINFO and Sociological Abstracts were searched on July 15, 2020 for studies published in English since January 2010. Study selection, critical appraisal (using the Joanna Briggs Institute's tools) and data extraction were performed in duplicate by two independent reviewers. SETTING: Nutrition interventions delivered to groups in community-based settings were eligible. Studies delivered in acute or long-term care settings were excluded. PARTICIPANTS: Community-dwelling older adults aged 55+ years. Studies targeting specific disease populations or promoting weight loss were excluded. RESULTS: Thirty-one experimental and quasi-experimental studies with generally unclear to high risk of bias were included. Interventions included nutrition education with behaviour change techniques (BCT) (e.g. goal setting, interactive cooking demonstrations) (n 21), didactic nutrition education (n 4), interactive nutrition education (n 2), food access (n 2) and nutrition education with BCT and food access (n 2). Group-based nutrition education with BCT demonstrated the most promise in improving food and fluid intake, nutritional status and healthy eating knowledge compared with baseline or control. The impact on mobility outcomes was unclear. CONCLUSIONS: Group-based nutrition education with BCT demonstrated the most promise for improving healthy eating among community-dwelling older adults. Our findings should be interpreted with caution related to generally low certainty, unclear to high risk of bias and high heterogeneity across interventions and outcomes. Higher quality research in group-based nutrition education for older adults is needed.