Strength training in older women: Early and late changes in whole muscle and single cells

Frontera, Walter R.; Hughes, Virginia; Krivickas, Lisa S.; Kim, Sang-Kyu; Foldvari, Mona; Roubenoff, Ronenn

doi:10.1002/mus.10480

Cited by 94 publications

(78 citation statements)

References 26 publications

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“…23 This sequence seems to be true of hypertrophy-inducing pharmacologic agents, and is the opposite of what occurs with resistance exercise training, in which strength increases first. 24 We have demonstrated that SMAD phosphorylation is frequently increased in the muscle of patients with sIBM, suggesting that at least part of the TGFb superfamily may be implicated in the pathophysiology of sIBM. The finding that SMAD2/3 was elevated still left unresolved whether inhibiting this pathway in particular would be sufficient to perturb the clinical consequence of sIBM.…”

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confidence: 81%

Treatment of sporadic inclusion body myositis with bimagrumab

et al. 2014

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Objective: To study activin signaling and its blockade in sporadic inclusion body myositis (sIBM) through translational studies and a randomized controlled trial. Methods:We measured transforming growth factor b signaling by SMAD2/3 phosphorylation in muscle biopsies of 50 patients with neuromuscular disease (17 with sIBM). We tested inhibition of activin receptors IIA and IIB (ActRII) in 14 patients with sIBM using one dose of bimagrumab (n 5 11) or placebo (n 5 3). The primary outcome was the change in right thigh muscle volume by MRI at 8 weeks. Lean body mass, strength, and function were secondary outcomes. Twelve of the patients (10 bimagrumab, 2 placebo) participated in a subsequent 16-week observation phase.Results: Muscle SMAD2/3 phosphorylation was higher in sIBM than in other muscle diseases studied (p 5 0.003). Eight weeks after dosing, the bimagrumab-treated patients increased thigh muscle volume (right leg 16.5% compared with placebo, p 5 0.024; left leg 17.6%, p 5 0.009) and lean body mass (15.7% compared with placebo, p 5 0.014). Subsequently, bimagrumabtreated patients had improved 6-minute walking distance, which peaked at 16 weeks (114.6%, p 5 0.008) compared with placebo. There were no serious adverse events; the main adverse events with bimagrumab were mild acne and transient involuntary muscle contractions.Conclusions: Transforming growth factor b superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. Inhibition of ActRII increased muscle mass and function in this pilot trial, offering a potential novel treatment of sIBM. Classification of evidence:This study provides Class I evidence that for patients with inclusion body myositis, bimagrumab increases thigh muscle volume at 8 weeks. Neurology ® 2014;83:2239-2246 GLOSSARY ActRII 5 activin receptors IIA and IIB; DXA 5 dual-energy x-ray absorptiometry; LBM 5 lean body mass; pSMAD2/3 5 phosphorylated SMAD2/3; QMT 5 quantitative muscle testing; sIBM 5 sporadic inclusion body myositis; 6MWD 5 6-minute walking distance; TGFb 5 transforming growth factor b; TMV 5 thigh muscle volume.Sporadic inclusion body myositis (sIBM) is a slowly progressive degenerative and inflammatory skeletal muscle disease beginning in middle or later life.1 Its clinical features include a specific pattern of muscle involvement (preferential weakness of finger flexors and knee extensors) accompanied by progressive muscle atrophy, distinctive microscopic pathology including endomysial inflammation and rimmed vacuoles, and a recently identified serum autoantibody (against cytosolic 59-nucleotidase 1A) biomarker.2-4 Despite a prominent adaptive immune response characterized by antigen-stimulated B-and T-cell maturation and prominent infiltration into muscle of immune system cells, sIBM is highly refractory to immunosuppressive therapies studied to date. 2Members of the transforming growth factor b (TGFb) superfamily of ligands signal through a heterodimeric receptor system.5 They first bind a type II receptor, such as the TGFb...

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confidence: 81%

Treatment of sporadic inclusion body myositis with bimagrumab

et al. 2014

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“…In addition, endurance (97,98,(104)(105)(106)(107)(108)(109)(110) exercise was shown to enhance the skeletal muscle oxidative capacity, resulting in greater endurance capacity (5,120) . Although the muscle regenerative capacity seems to decline at a more advanced age, the reduced satellite cell pool size (119) does not compromise the capacity for muscle hypertrophy to occur even at an advanced age (121)(122)(123) and resistance exercise training was shown to increase muscle fibre size (124)(125)(126)(127) .…”

Section: Long-term Interventionsmentioning

confidence: 99%

Dietary protein and exercise training in ageing

Koopman

2010

Proc. Nutr. Soc.

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Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk for developing chronic metabolic diseases such as diabetes. The age-related loss of skeletal muscle mass results from a chronic disruption in the balance between muscle protein synthesis and degradation. As basal muscle protein synthesis rates are likely not different between healthy young and elderly human subjects, it was proposed that muscles from older adults lack the ability to regulate the protein synthetic response to anabolic stimuli, such as food intake and physical activity. Indeed, the doseresponse relationship between myofibrillar protein synthesis and the availability of essential amino acids and/or resistance exercise intensity is shifted down and to the right in elderly human subjects. This so-called 'anabolic resistance' represents a key factor responsible for the age-related decline in skeletal muscle mass. Interestingly, long-term resistance exercise training is effective as a therapeutic intervention to augment skeletal muscle mass, and improves functional performance in the elderly. The consumption of different types of proteins, i.e. protein hydrolysates, can have different stimulatory effects on muscle protein synthesis in the elderly, which may be due to their higher rate of digestion and absorption. Current research aims to elucidate the interactions between nutrition, exercise and the skeletal muscle adaptive response that will define more effective strategies to maximise the therapeutic benefits of lifestyle interventions in the elderly. Sarcopenia: Nutrition: Exercise training: Muscle hypertrophyThe preservation of muscle function is crucial for maintaining an independent lifestyle and the capacity to perform the activities of daily living in the elderly. One of the important factors in the loss of functional performance is the progressive loss of skeletal muscle mass with ageing, called 'sarcopenia' (1)(2)(3) . This apparent muscle wasting in elderly human subjects occurs at a rate of about 0 . 5-1 . 0% per year starting at about 40 years of age. Lean muscle mass contributes up to about 50% of the total body mass of young adults but can decline to 25% by 75-80 years of age (4,5) . The loss of muscle mass is most notable in the lower limb muscles, with the cross-sectional area of the vastus lateralis reduced by as much as 40% at the age of 80 years (6) . Sarcopenia is associated with a three-to fourfold increased likelihood of disabilities and the loss of muscle mass especially in the lower limbs is associated with an increased risk of falls and impairment in the ability to perform routine activities.The loss of muscle mass is viewed as a largely inevitable and undesirable consequence of ageing (7) , with muscle loss estimated to affect 30% of people older than 60 years and >50 % of those older than 80 years (1) . Demographic studies indicate that the world's population aged 60 years and above will triple within the next 50 years, and the su...

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“…Indeed, numerous studies have demonstrated that resistance training is an effective measure to counteract sarcopenia in both healthy and frail older adults (Carmeli et al 2000;Charette et al 1991;Ferri et al 2003;Frontera et al 1988Frontera et al , 2000Frontera et al , 2003. It would appear that with an appropriate and effective exercise regimen, older adults may expect gains of 5-10% muscle CSA, accompanied by increases of 20-100% or more in muscle strength, depending on the muscle group under investigation.…”

Section: Muscle Size and Strength Changesmentioning

confidence: 99%

Influence of exercise intensity in older persons with unchanged habitual nutritional intake: skeletal muscle and endocrine adaptations

Onambélé-Pearson

Breen

Stewart

2010

AGE

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Long-term adherence to training programmes is difficult to attain. Yet, the benefits of exercise to general health and well-being are undeniable. Any measure to demonstrate the minimum required exercise for maximal benefit to a person is a promising avenue towards increasing the uptake and adherence to physical activity for the general public. The purpose of this study was to compare the effects of two different intensities of resistance training in healthy older adults. We hypothesised that compared to high-intensity resistance exercise, relatively low training intensity could also improve in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals. Thirty (out of a possible 34 recruited) older adults were randomly assigned to low (LowR, i.e. ∼40% one repetition maximum (1RM)) versus high-resistance training (HighR, i.e. ∼80% 1RM) for 12 weeks. Neither intervention significantly impacted upon body composition markers including: body mass index (BMI), waist/hip ratio and bioelectric impedance. Muscle strength data showed an advantage for the HighR protocol with 51±4% and 22.4±10.2% (P<0.05) improvements in 1RM strength and bilateral knee extension torque, respectively, compared with 17±1% and 10.3±4.7% (P<0.05) increments in 1RM strength and bilateral torque in the LowR group. Unilateral torque did not change significantly in either group. Quadriceps muscle thickness data also showed a significantly greater benefit of the HighR protocol (5.8±2.6% increase) compared with the LowR protocol (no change). Functional ability tests, including Get-up-and-go (GUG), Standing from lying and the 6-min walk, showed changes of −11.6 ± 4.8%, −15.6% and 8.5±1.7% (P<0.05), respectively, in HighR compared with only one significant improvement in the LowR, namely a −10.8±3% (P<0.05) improvement in the GUG test. Overnight fasting serum levels of IGFBP-3 increased, NPY decreased and TNF-α decreased significantly in the LowR group. Serum levels of glucose increased and NPY decreased significantly in HighR. Circulating levels of I, IL-6 and IGF-1 did not change with either intervention. In vivo physiologic changes show functional advantages for older persons carrying out AGE (2010) 32:139-153

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Strength training in older women: Early and late changes in whole muscle and single cells

Cited by 94 publications

References 26 publications

Treatment of sporadic inclusion body myositis with bimagrumab

Treatment of sporadic inclusion body myositis with bimagrumab

Dietary protein and exercise training in ageing

Influence of exercise intensity in older persons with unchanged habitual nutritional intake: skeletal muscle and endocrine adaptations

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