A Mechanism by Which Calorie Restriction Improves Muscle Stem Cell Activity in Aging

It is known that the practice of calorie restriction slows the characteristic loss of muscle mass and strength that takes place with age, leading to sarcopenia. Researchers here identify a mechanism by which lowered calorie intake improves muscle stem cell activity in the context of aging. Other work suggests that declining stem cell activity is the most important factor in the development of sarcopenia. An understanding of the mechanisms involved may lead to improved ways to mimic the specific protective effects of calorie restriction in this context.

In this study, we used a calorie restriction (CR) model of elderly mice with muscle-specific 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) knockout mice and 11β-HSD1 overexpression mice to confirm that CR can delay muscle aging by inhibiting 11β-HSD1 which can transform inactive glucocorticoid (cortisone) into active glucocorticoid (cortisol). The ability of self-renewal and differentiation into muscle fibers of these mouse muscle stem cells (MuSCs) was observed in vitro. Additionally, the mitochondrial function and mitochondrial ATP production capacity of MuSCs were measured by mitochondrial oxygen consumption.

It was found that the 11β-HSD1 expression level was increased in age-related muscle atrophy. Overexpression of 11β-HSD1 led to muscle atrophy in young mice, and 11β-HSD1 knockout rescued age-related muscle atrophy. Moreover, CR in aged mice reduced the local effective concentration of glucocorticoid through 11β-HSD1, thereby promoting the mitochondrial function and differentiation ability of MuSCs.

Together, our findings highlight promising sarcopenia protection with CR in older ages. Furthermore, we speculated that targeting an 11β-HSD1-dependent metabolic pathway may represent a novel strategy for developing therapeutics against age-related muscle atrophy.

Link: https://doi.org/10.3389/fmed.2022.1027055

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