Maximus Peto’s Commentary
This group reported some associations between AMPK activation and what appeared to be prevention or reversal of cellular senescence. I found the exercise part of this study particularly interesting: treadmill exercise in mice reduced p16 and p21 expression in older sedentary mice. Could this be representative of a reversal of senescence? If so, how might it be recapitulated in other tissue types? In response to a similar study I reported on, if I recall correctly, Aubrey mentioned that exercise reducing/reversing senescence was not surprising because exercise would help nutrient uptake. If that’s true, I wonder whether other tissues (e.g. skin) might experience increased senescence because of relatively poor nutrient uptake (perhaps after adolescence when growth factors that facilitate nutrient uptake decline). For example, I have yet to figure out how to flex my skin (to improve nutrient uptake)! Aubrey and others, what do you think of this concept?
Exercise-induced AMPK activation is involved in delay of skeletal muscle senescence.
Biochem Biophys Res Commun. 2019 May 7;512(3):604-610.
Yoon KJ, Zhang D, Kim SJ, Lee MC, Moon HY
PubMed publication date (edat): 3/27/2019
Accumulation of senescent cells leads to aging related phenotypes in various organs. Sarcopenia is a frequently observed aging-related disease, which is associated with the loss of muscle mass and functional disability. Physical activity represents the most critical treatment method for preventing decreased muscle size, mass and strength. However, the underlying mechanism as to how physical activity provides this beneficial effect on muscle function has not yet been fully understood. In particular, one unresolved question about aging is how the boost in catabolism induced by aerobic exercise affects skeletal muscle atrophy and other senescence phenotypes. Here we show that pre-activation of AMPK with the AMPK activator, AICAR can mitigate the diminished cellular viability of skeletal muscle cells induced by doxorubicin, which accelerates senescence through free radical production. Pre-incubation for 3 h with AICAR decreased doxorubicin-induced phosphorylation of AMPK in a differentiated skeletal muscle cell line. Accordingly, cellular viability of skeletal muscle cells was recovered in the cells pre-treated with AICAR then administered doxorubicin as compared to that of doxorubicin-only treatment. In accordance with the results of cellular experiments, we verified that 4 weeks of treadmill exercise decreased the senescence marker, p16 and p21 in 19-month-old mice compared to sedentary mice. In this study, we provide new evidence that prior activation of AMPK can reduce doxorubicin induced cell senescence phenotypes. The evidence in this paper suggest that aerobic exercise-activated catabolism in the skeletal muscle may prevent cellular senescence, partially through the cell cycle regulation.