Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy

Bamman, Marcas M.; Roberts, Brandon M.; Adams, Gregory R.

doi:10.1101/cshperspect.a029751

Cited by 64 publications

(42 citation statements)

References 79 publications

(114 reference statements)

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“…No prescription induces homogeneous adaptations among recipients, and studies of inter-individual response heterogeneity by us 18,21,37,38 and others (reviewed in 39 ) have yielded valuable insight. The 3-cluster K-means cluster analysis of the primary outcome (change in TMM) – summarized in Figure 3 – revealed clinically meaningful findings, as a remarkable 88% of HLH recipients were clustered as positive responders including two extreme responders.…”

Section: Discussionmentioning

confidence: 99%

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy

Stec

Thalacker‐Mercer

Mayhew

et al. 2017

Experimental Gerontology

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Purpose The myriad consequences of age-related muscle atrophy include reduced muscular strength, power, and mobility; increased risk of falls, disability, and metabolic disease; and compromised immune function. At its root, aging muscle atrophy results from a loss of myofibers and atrophy of the remaining type II myofibers. The purpose of this trial (NCT02442479) was to titrate the dose of resistance training (RT) in older adults in an effort to maximize muscle regrowth and gains in muscle function. Methods A randomized, four-arm efficacy trial in which four, distinct exercise prescriptions varying in intensity, frequency, and contraction mode/rate were evaluated: (1) high-resistance concentric-eccentric training (H) 3 d/wk (HHH); (2) H training 2 d/wk (HH); (3) 3 d/wk mixed model consisting of H training 2 d/wk separated by 1 bout of low-resistance, high-velocity, concentric only (L) training (HLH); and (4) 2 d/wk mixed model consisting of H training 1 d/wk and L training 1 d/wk (HL). Sixty-four randomized subjects (65.5 ± 3.6y) completed the trial. All participants completed the same 4 wk of pre-training consisting of 3 d/wk followed by 30 wk of randomized RT. Results The HLH prescription maximized gains in thigh muscle mass (TMM, primary outcome) and total body lean mass. HLH also showed the greatest gains in knee extension maximum isometric strength, and reduced cardiorespiratory demand during steady-state walking. HHH was the only prescription that led to increased muscle expression of pro-inflammatory cytokine receptors and this was associated with a lesser gain in TMM and total body lean mass compared to HLH. The HL prescription induced minimal muscle regrowth and generally lesser gains in muscle performance vs. the other prescriptions. Major Conclusions The HLH prescription offers distinct advantages over the other doses, while the HL program is subpar. Although limited by a relatively small sample size, we conclude from this randomized dose-response trial that older adults benefit greatly from 2 d/wk high-intensity RT, and may further benefit from inserting an additional weekly bout of low-load, explosive RT. Trial Registration ClinicalTrials.gov NCT02442479

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Section: Discussionmentioning

confidence: 99%

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy

Stec

Thalacker‐Mercer

Mayhew

et al. 2017

Experimental Gerontology

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“…Abnormal protein degradation and muscle atrophy generally occur with genetic mutation (DMD) (32), hormone exposure (glucocorticoid) (33), or disease (cachexia) (34). Many studies have shown that appropriate exercise can induce muscle hypertrophy and is also an effective way to rescue muscle atrophy (35)(36)(37). Interestingly, clinical studies demonstrated that exercise is associated with increased serum AKG (38), which previously has been shown to down-regulate protein degradation-related genes in the skeletal muscle of mice (17).…”

Section: Discussionmentioning

confidence: 99%

α‐Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway

et al. 2017

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Skeletal muscle atrophy due to excessive protein degradation is the main cause for muscle dysfunction, fatigue, and weakening of athletic ability. Endurance exercise is effective to attenuate muscle atrophy, but the underlying mechanism has not been fully investigated. α-Ketoglutarate (AKG) is a key intermediate of tricarboxylic acid cycle, which is generated during endurance exercise. Here, we demonstrated that AKG effectively attenuated corticosterone-induced protein degradation and rescued the muscle atrophy and dysfunction in a Duchenne muscular dystrophy mouse model. Interestingly, AKG also inhibited the expression of proline hydroxylase 3 (PHD3), one of the important oxidoreductases expressed under hypoxic conditions. Subsequently, we identified the β adrenergic receptor (ADRB2) as a downstream target for PHD3. We found AKG inhibited PHD3/ADRB2 interaction and therefore increased the stability of ADRB2. In addition, combining pharmacologic and genetic approaches, we showed that AKG rescues skeletal muscle atrophy and protein degradation through a PHD3/ADRB2 mediated mechanism. Taken together, these data reveal a mechanism for inhibitory effects of AKG on muscle atrophy and protein degradation. These findings not only provide a molecular basis for the potential use of exercise-generated metabolite AKG in muscle atrophy treatment, but also identify PHD3 as a potential target for the development of therapies for muscle wasting.-Cai, X., Yuan, Y., Liao, Z., Xing, K., Zhu, C., Xu, Y., Yu, L., Wang, L., Wang, S., Zhu, X., Gao, P., Zhang, Y., Jiang, Q., Xu, P., Shu, G. α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway.

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“…In human subjects hypertrophy may be related to the size of the SC‐pool prior to training or the expansion of the SC‐pool associated with training . However, the necessity of SCs for hypertrophy is widely debated …”

Section: Introductionmentioning

confidence: 99%

Preserved capacity for satellite cell proliferation, regeneration, and hypertrophy in the skeletal muscle of healthy elderly men

et al. 2020

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Blunted muscle hypertrophy and impaired regeneration with aging have been partly attributed to satellite cell (SC) dysfunction. However, true muscle regeneration has not yet been studied in elderly individuals. To investigate this, muscle injury was induced by 200 electrically stimulated (ES) eccentric contractions of the vastus lateralis (VL) of one leg in seven young (20-31 years) and 19 elderly men (60-73 years).This was followed by 13 weeks of resistance training (RT) for both legs to investigate the capacity for hypertrophy. Muscle biopsies were collected Pre-and Post-RT, and 9 days after ES, for immunohistochemistry and RT-PCR. Hypertrophy was assessed by MRI, DEXA, and immunohistochemistry. Overall, surprisingly comparable responses were observed between the young and elderly. Nine days after ES, Pax7+ SC number had doubled (P < .05), alongside necrosis and substantial changes in expression of genes related to matrix, myogenesis, and innervation (P < .05). Post-RT, VL cross-sectional area had increased in both legs (~15%, P < .05) and SCs/type II fiber had increased ~2-4 times more with ES+RT vs RT alone (P < .001). Together these novel findings demonstrate "youthful" regeneration and hypertrophy responses in human elderly muscle. Furthermore, boosting SC availability in healthy elderly men does not enhance the subsequent muscle hypertrophy response to RT. K E Y W O R D S heavy resistance training, human, myofiber necrosis, myogenic progenitor cells, in vivo myogenesis, Sarcopenia | 6419 KARLSEN Et AL. F I G U R E 1 Study design. Overview of the study design indicating the timing of muscle biopsies, blood sampling, electrical stimulation (ES), measures of muscle soreness, maximal muscle strength (MVC), magnetic resonance imaging (MRI), dual energy X-ray absorptiometry (DXA), and resistance training (RT) during the Pre-and Post-test. One leg (ES+RT leg) completed 200 electrically stimulated eccentric contractions (ES) followed by 13 weeks resistance training (RT), the other leg performed RT only. A biopsy was collected in both legs at Pre and Post, and an additional biopsy was collected in the ES+RT leg at Day 9 after ES | 6421 KARLSEN Et AL.

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Molecular Regulation of Exercise-Induced Muscle Fiber Hypertrophy

Cited by 64 publications

References 79 publications

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy

α‐Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway

Preserved capacity for satellite cell proliferation, regeneration, and hypertrophy in the skeletal muscle of healthy elderly men

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