Improved autophagy is implicated in many of the approaches shown to slow aging in animal models. An open question is whether more targeted approaches to altering the regulation of autophagy in aged cells can improve matters to a greater degree than, for example, exercise or the practice of calorie restriction, both of which are known to produce general improvements in autophagy. Researchers here show that improvement of autophagy via increased expression of TRP53INP2 in old mice can reduce the age-related loss muscle mass and function that leads to sarcopenia. It seems an interesting target for further development of therapies.
Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed.
Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and human skeletal muscle. Importantly, chronic activation of autophagy by muscle-specific overexpression of TRP53INP2 prevents sarcopenia and the decline of muscle function in mice. Acute re-expression of TRP53INP2 in aged mice also improves muscle atrophy, enhances mitophagy, and reduces reactive oxygen species (ROS) production. In humans, high levels of TP53INP2 in muscle are associated with increased muscle strength and healthy aging. Our findings highlight the relevance of an active muscle autophagy in the maintenance of muscle mass and prevention of sarcopenia.
Link: https://doi.org/10.1...27.2024.2333717
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