Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay

Bergen, H. Robert; Farr, Joshua N.; Vanderboom, Patrick M.; Atkinson, Elizabeth J.; White, Thomas A.; Singh, Ravinder J.; Khosla, Sundeep; LeBrasseur, Nathan K.

doi:10.1186/s13395-015-0047-5

Cited by 111 publications

(125 citation statements)

References 42 publications

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“…Along the same lines, in some studies, muscle mass was inversely correlated with serum myostatin levels [11]. However, more recent studies have shown a positive correlation between lean mass or muscle strength and myostatin [10, 12]. …”

Section: Introductionmentioning

confidence: 80%

“…Accordingly, relative muscle mass was inversely correlated with serum myostatin [11]. However, other studies reported that the concentration of myostatin decreases with age in men [12, 13]. Few studies have analyzed the interaction between frailty indexes and serum myostatin levels; some found higher levels of myostatin in physically frail women than in their non-frail counterparts [11, 30].…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, some studies found higher myostatin concentrations in older men and women [11]; others found that the concentration of myostatin decreased with age in men but not in women [12-14]. Along the same lines, in some studies, muscle mass was inversely correlated with serum myostatin levels [11].…”

Section: Introductionmentioning

confidence: 99%

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Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

et al. 2018

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Background: Myostatin has been proposed as a candidate biomarker for frailty and sarcopenia. However, the relationship of myostatin with these conditions remains inconclusive. Objective: To determine the association of serum myostatin concentration with body composition, physical fitness, physical activity level, and frailty in long-term nursing home residents. We also aimed to ascertain the effect of an exercise program on myostatin levels. Methods: We obtained study data on 112 participants from long-term nursing homes. Participants were randomly assigned to a control or an intervention group and performed a 6-month multicomponent exercise program. Serum myostatin levels were analyzed by ELISA. Assessments also included body composition (anthropometry and bioelectrical impedance), physical fitness (Senior Fitness Test), physical activity level (accelerometry), and frailty (Fried frailty criteria, Clinical Frailty Scale, and Tilburg frailty indicator). Results: The concentration of myostatin at baseline was positively correlated with: a leaner body composition (p < 0.05), and a higher number of steps per day and light and moderate-vigorous physical activity in women (p < 0.005); greater upper and lower limb strength, endurance, and poorer flexibility (p < 0.05) in men; and better performance (less time) in the 8-ft timed up-and-go test in both women (p < 0.01) and men (p < 0.005). We observed higher concentrations of serum myostatin in non-frail than in frail participants (p < 0.05). Additionally, we found that the implemented physical exercise intervention, which was effective to improve physical fitness, increased myostatin concentration in men (p < 0.05) but not in women. The improvements in physical condition were related with increases in serum myostatin only in men (p < 0.05–0.01). Conclusions: Higher serum levels of myostatin were found to be associated with better physical fitness. The improvements in physical fitness after the intervention were positively related to increases in myostatin concentrations in men. These results seem to rule out the idea that high serum myostatin levels are indicative of frailty in long-term nursing home residents. However, although the direction of association was opposite to that expected for the function of myostatin, the use of this protein as a biomarker for physical fitness, rather than frailty, merits further study.

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Section: Introductionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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Serum Myostatin Levels Are Higher in Fitter, More Active, and Non-Frail Long-Term Nursing Home Residents and Increase after a Physical Exercise Intervention

et al. 2018

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“…Skeletal muscle mass is regulated by myostatin, a member of the transforming growth factor‐β superfamily and a potent negative regulator of muscle growth 6, 7, 8. Myostatin is upregulated in obesity and downregulated by exercise 9, 10, 11, 12. Targeted inhibition of myostatin, genetically or pharmaceutically, has had promising results in improving cardiometabolic health (namely, glucose tolerance) and preventing/restoring muscle mass in rodents and humans 8, 13, 14, 15, 16, 17, 18…”

Section: Introductionmentioning

confidence: 99%

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity

Butcher

Mintz

Larion

et al. 2018

JAHA

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BackgroundObesity compromises cardiometabolic function and is associated with hypertension and chronic kidney disease. Exercise ameliorates these conditions, even without weight loss. Although the mechanisms of exercise's benefits remain unclear, augmented lean body mass is a suspected mechanism. Myostatin is a potent negative regulator of skeletal muscle mass that is upregulated in obesity and downregulated with exercise. The current study tested the hypothesis that deletion of myostatin would increase muscle mass and reduce blood pressure and kidney injury in obesity.Methods and ResultsMyostatin knockout mice were crossed to db/db mice, and metabolic and cardiovascular functions were examined. Deletion of myostatin increased skeletal muscle mass by ≈50% to 60% without concomitant weight loss or reduction in fat mass. Increased blood pressure in obesity was prevented by the deletion of myostatin, but did not confer additional benefit against salt loading. Kidney injury was evident because of increased albuminuria, which was abolished in obese mice lacking myostatin. Glycosuria, total urine volume, and whole kidney NOX‐4 levels were increased in obesity and prevented by myostatin deletion, arguing that increased muscle mass provides a multipronged defense against renal dysfunction in obese mice.ConclusionsThese experimental observations suggest that loss of muscle mass is a novel risk factor in obesity‐derived cardiovascular dysfunction. Interventions that increase muscle mass, either through exercise or pharmacologically, may help limit cardiovascular disease in obese individuals.

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“…Circulating sclerostin appears to correlate with total body bone mass (i.e., the number of osteocytes), and levels are higher in men than in women [5]. Furthermore, several studies show a poor correlation between circulating sclerostin versus expression in bone [6]. Thus, one explanation for higher myostatin levels in fitter, less frail individuals might be its known (although moderate) correlation with total muscle mass [7].…”

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confidence: 99%