Myostatin insufficiency produces stronger mice who live 15% longer

Fighting aging reports that loss of myostatin mutations in mice produce extended life spans, but too much suppression of myostatin may remove that benefit due to the cardiac issues that can accompany an overly large heart.

Aging Cell Journal -Haploinsufficiency of myostatin protects against aging-related declines in muscle function and enhances the longevity of mice

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.

The mechanism behind the increased longevity of MSTN+/− mice is not known, but inhibition of myostatin can reduce systemic inflammatory proteins and body fat

Sarcopenia is the pathological loss in muscle mass and strength that occurs with aging. In mice, muscle mass and force production slowly decreases from adulthood (6–9 months of age) to old age (22–24 months), with a rapid deterioration present once mice reach oldest-old ages (over 26–28 months). There is also an aging-associated increase in collagen accumulation which can diminish force production. In humans, muscle mass is positively correlated with a greater longevity, and the rapid decrease in muscle mass and strength that occurs toward the end of the lifespan can lead to severe disability and reduced quality of life.

Myostatin is a negative regulator of skeletal muscle mass, with adult MSTN−/− mice displaying up to a twofold increase in muscle mass. Myostatin induces atrophy by upregulating the E3 ubiquitin ligases atrogin-1 and MuRF-1 and by inhibiting the IGF-1 pathway. 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 , 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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