Abstract
The molecular mechanisms behind aging-related declines in muscle function are not well understood, but the growth factor myostatin (MSTN) appears to play an important role in this process. Additionally, epidemiological studies have identified a positive correlation between skeletal muscle mass and longevity. Given the role of myostatin in regulating muscle size, and the correlation between muscle mass and longevity, we tested the hypotheses that the deficiency of myostatin would protect oldest-old mice (28–30 months old) from an aging-related loss in muscle size and contractility, and would extend the maximum lifespan of mice. We found that MSTN+/− and MSTN−/− mice were protected from aging-related declines in muscle mass and contractility. While no differences were detected between MSTN+/+ and MSTN−/− mice, MSTN+/− mice had an approximately 15% increase in maximal lifespan. These results suggest that targeting myostatin may protect against aging-related changes in skeletal muscle and contribute to enhanced longevity.
Highlights
Sarcopenia is the pathological loss in muscle mass and strength that occurs with aging (Gumucio & Mendias, 2013)
Myostatin is a negative regulator of skeletal muscle mass, with adult MSTNÀ/À mice displaying up to a twofold increase in muscle mass (Gumucio & Mendias, 2013)
As the role of myostatin in regulating muscle function in oldest-old mice had not previously been studied, and there is a positive correlation between muscle mass and longevity in humans (Miller et al, 2002), we tested the hypotheses that oldest-old male myostatin-deficient mice would have improved muscle force production compared to wild-type mice and that the deficiency of myostatin would increase the maximum lifespan of mice
Summary
Sarcopenia is the pathological loss in muscle mass and strength that occurs with aging (Gumucio & Mendias, 2013). Myostatin is a negative regulator of skeletal muscle mass, with adult MSTNÀ/À mice displaying up to a twofold increase in muscle mass (Gumucio & Mendias, 2013). As the role of myostatin in regulating muscle function in oldest-old mice had not previously been studied, and there is a positive correlation between muscle mass and longevity in humans (Miller et al, 2002), we tested the hypotheses that oldest-old male myostatin-deficient mice would have improved muscle force production compared to wild-type mice and that the deficiency of myostatin would increase the maximum lifespan of mice.
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