Resistance Exercise Training In Older Adults Research Articles

Network Analysis Identifies Circulating MicroRNA Associated With Muscle Mass Gains In Resistance Trained Older Adults

Purpose: Age related muscle loss (sarcopenia) is a major contributor to functional disability and all-cause mortality. Rescuing muscle mass in older adults has been most effective with resistance exercise training (RT). We have previously demonstrated that 3d/wk of heavy RT in older adults may blunt the hypertrophic response to progressive resistance training. We postulate that this effect may be mediated by epigenetic factors, such as, microRNA (miRNA), resulting in impaired muscle mass growth. We hypothesize that insufficient recovery time may contribute to attenuated hypertrophic responses to RT if intensive loading occurs too frequently (i.e. 3 d/wk). The present study is a follow up molecular analysis of two RT cohorts from our previous clinical trial (NCT02442479) in which optimal exercise dose for aging individuals (60-75y) was determined from four RT cohorts. That trial determined that a dose consisting of 2 d/wk high-intensity RT separated by a low-intensity, concentric only day (HLH) was superior to 3 d/wk high-intensity RT (HHH) for thigh lean mass gains. Methods: The present study sequenced circulating miRNA from serum exosomes pre- and post- 35 weeks of RT in 19 individuals that underwent either HLH or HHH RT. Subsequent analysis was performed via weighted gene co-expression network analysis (WGCNA) to identify modules of eigengenes with miRNA membership correlated with treatment and thigh lean mass gains. Network analysis and visualization of these modules were performed. Results and Conclusion: WGCNA identified modules correlated with treatment (p = 0.03, p = 0.05) and with thigh lean mass gains (p = 0.006 and p = 0.01) at the final time point (35wk). Pathway analysis provides insight into regulated pathways that may be attributed RT frequency and subsequent magnitude of thigh lean mass hypertrophy between the two treatment groups. Altogether, this analysis reports on a molecular exercise response in aging individuals that may better inform exercise dose optimization, as well as, deepen our understanding of inter-individual response heterogeneity. Supported by T32HD071866 and P2CHD086851.

Low Intake of Choline Is Associated with Diminished Strength and Lean Mass Gains in Older Adults.

Choline is an essential micronutrient for many physiological processes related to exercise training including biosynthesis of acetylcholine. Though dietary choline intake has been studied in relation to endurance training and performance, none have studied it during resistance exercise training (RET) in older adults. The objective of the study was to examine the relationship between choline intake and muscle responses to RET in older adults. Forty-six, 60-69-year-old individuals (M=19, F=27) underwent 12 weeks of RET (3x/week, 3 sets, 8-12 reps, 75% of maximum strength [1RM], 8 exercises). Body composition (DEXA) and 1RM tests were performed before and after training. After analyzing 1,656 diet logs (3x/week, 46 participants, 12 weeks), participants' mean choline intakes were categorized into three groups: Low (2.9-5.5 mg/kg lean/d), Med-Low (5.6-8.0 mg/kg lean/d), or Adequate (8.1-10.6 mg/kg lean/d). These correspond to <50%, ~63%, and ~85% of Adequate Intake (AI) for choline, respectively. Gains in composite strength (leg press + chest press 1RM) were significantly lower in the Low group compared with the other groups (Low: 30.9 ± 15.1%, Med-Low: 70.3 ± 48.5%, Adequate: 81.9 ± 68.4%; p=0.004). ANCOVA with cholesterol, protein, or other nutrients did not alter this result. Reduced gains in lean mass were also observed in the Low group, compared with higher choline intake of 5.6-10.6 mg/kg lean/d (1.3 ± 0.6% vs. 3.2 ± 0.6%, p<0.05). These data suggest that this population of older adults does not consume adequate choline and lower choline intake is negatively and independently associated with muscle responses to RET.

Potential Mechanisms Of Inflammation-induced Attenuated Muscle Hypertrophy Following 3-d/wk High-intensity Resistance Training Among Aged Individuals

PURPOSE: Aging related loss in muscle mass (sarcopenia) is major contributor to functional disability and all-cause mortality. Resistance exercise training (RT) is an established treatment for age-related losses in muscle mass, strength, and power. However, we have previously found that 3 d/wk of heavy RT in older adults may blunt the hypertrophic response to progressive resistance training. We postulate that this effect is mediated by skeletal muscle inflammation, indicated by heightened expression of TNFR1 and TWEAK-R. Typically, acute exercise induced inflammation is beneficial to muscle hypertrophy, and this regimen has been shown to be well tolerated by young adults. However, impaired exercise tolerance and adaptability sometimes demonstrated in older adults may be mediated by increased basal muscle inflammatory burden, coupled with an exaggerated inflammatory response to muscle loading. We hypothesize that this phenomenon in the aging cohort may impair hypertrophic responses to RT if intensive loading occurs too frequently (i.e. 3 d/wk). METHODS: This study builds on a previous clinical trial conducted by our lab (NCT02442479), analyzing muscle hypertrophy in a four-arm, randomized dose-response trial to determine optimal exercise treatment for aging individuals (60-75 y). For this follow-up molecular analysis, we analyzed two of the groups of interest that underwent either 3 d/wk mixed model consisting of two days high-intensity training days separated by one low-intensity, concentric only day (HLH, n = 18) or 3 d/wk high-intensity training regimen (HHH, n = 18). Skeletal muscle biopsies were collected before and after 35 weeks of training in either HLH or HHH. Muscle and serum-derived miRNA-Seq is underway to identify potentially novel regulators of muscle hypertrophy and inflammation, accompanied by targeted muscle analysis of key inflammatory pathways (e.g., TNF/TWEAK-NFkB, IL-6-STAT3). RESULTS AND CONCLUSION: We expect that results from this study will advance our understanding of the role of inflammation in blunting muscle hypertrophy in aging adults, including a better understanding of both dose optimization and inter-individual response heterogeneity. Supported by T32HD071866 and UAB Center for Exercise Medicine.

Resistance exercise training promotes fiber type-specific myonuclear adaptations in older adults.

Aging induces physiological decline in human skeletal muscle function and morphology, including type II fiber atrophy and an increase in type I fiber frequency. Resistance exercise training (RET) is an effective strategy to overcome muscle mass loss and improve strength, with a stronger effect on type II fibers. In the present study, we sought to determine the effect of a 12-wk progressive RET program on the fiber type-specific skeletal muscle hypertrophic response in older adults. Nineteen subjects [10 men and 9 women (71.1 ± 4.3 yr)] were studied before and after the 12-wk program. Immunohistochemical analysis was used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell abundance, myonuclear content, and lipid droplet density. RET induced an increase in MyHC type II fiber frequency and a concomitant decrease in MyHC type I fiber frequency. Mean CSA increased significantly only in MyHC type II fibers (+23.3%, P < 0.05), but myonuclear content increased only in MyHC type I fibers (P < 0.05), with no change in MyHC type II fibers. Satellite cell content increased ~40% in both fiber types (P > 0.05). RET induced adaptations to the capillary supply to satellite cells, with the distance between satellite cells and the nearest capillary increasing in type I fibers and decreasing in type II fibers. Both fiber types showed similar decrements in intramuscular lipid density with training (P < 0.05). Our data provide intriguing evidence for a fiber type-specific response to RET in older adults and suggest flexibility in the myonuclear domain of type II fibers during a hypertrophic stimulus.NEW & NOTEWORTHY In older adults, progressive resistance exercise training (RET) increased skeletal muscle fiber volume and cross-sectional area independently of myonuclear accretion, leading to an expansion of the myonuclear domain. Fiber type-specific analyses illuminated differential adaptation; type II fibers underwent hypertrophy and exhibited myonuclear domain plasticity, whereas myonuclear accretion occurred in type I fibers in the absence of a robust hypertrophic response. RET also augmented satellite cell-capillary interaction and reduced intramyocellular lipid density to improve muscle quality.

The Effects of Choline Intake and Resistance Exercise Training on Strength Gains in Older Adults

PURPOSE: The micronutrient choline plays a major role in neurotransmission and skeletal muscle contraction. We conducted a randomized controlled trial to examine the effects of choline intake on skeletal muscle responses to resistance exercise training (RET) in older adults. METHODS: Three groups of 50 to 69-year-old generally healthy men and women (n=37, age=59.8 ± 6 y, height=168.4 ± 9 cm, weight=79.5 ± 16 kg, body fat=30.3 ± 10 kg, male/female=15/22) underwent 12 weeks of RET (3x/week, 3 sets, 8-12 reps, 70% of maximum strength [1RM]) and submitted >1,776 diet logs (>4x/week for 12 weeks, 37 subjects). Participants’ diets (mean choline intake: 5.9 mg/kg lean/d) were supplemented with 0.7 mg/kg lean/d (Low, n=13), 2.8 mg/kg lean/d (Med, n=11), or 7.5 mg/kg lean/d (High, n=13) of choline in the form of egg yolk. Body composition, 1RM, and blood tests were performed before and after training. RESULTS: ANCOVA tests showed Low choline intake, compared with Med or High choline intakes, resulted in significantly diminished gains in composite strength (leg press + chest press 1RM; Low: 19.4 ± 8.2%, Med: 46.8 ± 8.9%, High: 47.4 ± 8.1%, p=0.034) and thigh muscle quality (leg press 1RM / thigh lean mass; Low: 12.3 ± 9.6%, Med/ High: 46.4 ± 7.0%, p=0.010) after controlling for lean mass, protein, betaine, and vitamin B12. No differences were observed in lean mass gains, clinical markers of liver/muscle damage, or blood lipid profiles. CONCLUSION: These data indicate that low supplemental choline intake negatively affects strength gains with RET in older adults. This study was supported by U.S. Poultry and Egg Association.

Effect of Protein or Essential Amino Acid Supplementation During Prolonged Resistance Exercise Training in Older Adults on Body Composition, Muscle Strength, and Physical Performance Parameters: A Systematic Review

Objectives: Loss of muscle mass and strength with aging, sarcopenia, burdens many older adults, making identification of strategies on how to counteract it very relevant—especially to health care providers working in rehabilitation. The aim of this systematic review was to determine the effect of protein or essential amino acid (EAA) supplementation during prolonged resistance exercise training (RT) in older adults. No known stimulants of muscle protein synthesis, or ingredients with an effect on muscle strength/physical function, were allowed with the supplementation, differentiating this systematic review from others. Data sources and methods: In January 2017, 4 electronic databases and reference lists were searched for randomized controlled trials investigating the effect of protein or EAA supplementation during RT in older adults (mean age &gt;60 years) on outcomes of body composition, muscle strength, and physical performance. Study selection and data extraction were performed by 2 independent reviewers. Results Sixteen studies (1107 participants) fulfilled the eligibility criteria. Methodologic differences between the studies disallowed a meta-analysis. Of the 16 studies, 6 found significant effects on body composition (3 studies), muscle strength (3 studies), and physical performance (2 studies) measures. Conclusions The evidence is weak and inconsistent, as benefit of protein or EAA supplementation during RT in older adults is only shown in some studies. The findings indicate that frail/sarcopenic older adults might benefit more than healthy older adults. Further research is needed to allow an interpretation on the importance of study population and design. Trial registration: PROSPERO, Reg. no.: CRD42017063808. Registered April 14, 2017.

Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis

BackgroundSarcopenia, the loss of skeletal muscle mass during aging, increases the risk for falls and dependency. Resistance exercise (RE) training is an effective treatment to improve muscle mass and strength in older adults, but aging is associated with a smaller amount of training-induced hypertrophy. This may be due in part to an inability to stimulate muscle-protein synthesis (MPS) after an acute bout of RE. We hypothesized that older adults would have impaired mammalian target of rapamycin complex (mTORC)1 signaling and MPS response compared with young adults after acute RE.MethodsWe measured intracellular signaling and MPS in 16 older (mean 70 ± 2 years) and 16 younger (27 ± 2 years) subjects. Muscle biopsies were sampled at baseline and at 3, 6 and 24 hr after exercise. Phosphorylation of regulatory signaling proteins and MPS were determined on successive muscle biopsies by immunoblotting and stable isotopic tracer techniques, respectively.ResultsIncreased phosphorylation was seen only in the younger group (P< 0.05) for several key signaling proteins after exercise, including mammalian target of rapamycin (mTOR), ribosomal S6 kinase (S6K)1, eukaryotic initiation factor 4E-binding protein (4E-BP)1 and extracellular signal-regulated kinase (ERK)1/2, with no changes seen in the older group (P >0.05). After exercise, MPS increased from baseline only in the younger group (P< 0.05), with MPS being significantly greater than that in the older group (P <0.05).ConclusionsWe conclude that aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. These age-related differences may contribute to the blunted hypertrophic response seen after resistance-exercise training in older adults, and highlight the mTORC1 pathway as a key therapeutic target to prevent sarcopenia.