Regulation of apoptosis and autophagy in mouse and human skeletal muscle with aging and lifelong exercise training

Maja Munk Dethlefsen, Jens Frey Halling, Henrik D. Møller, Peter Plomgaard, Birgitte Regenberg, Stine Ringholm, Henriette Pilegaard*

*Corresponding author af dette arbejde
42 Citationer (Scopus)

Abstract

Exercise training has been reported to prevent the age-induced decline in muscle mass and fragmentation of mitochondria, as well as to affect autophagy and mitophagy. The interaction between these pathways during aging as well as the similarity between such changes in human and mouse skeletal muscle is however not fully understood. Therefore the aim of the present study was to test the hypothesis that cellular degradation pathways, including apoptosis, autophagy and mitophagy are coordinately regulated in mouse and human skeletal muscle during aging and lifelong exercise training through a PGC-1α-p53 axis. Muscle samples were obtained from young untrained, aged untrained and aged lifelong exercise trained men, and from whole-body PGC-1α knockout mice and their littermate controls that were either lifelong exercise trained or sedentary young and aged. Lifelong exercise training prevented the aging-induced reduction in PGC-1α p53 and p21 mRNA as well as the increase in LC3II and BNIP3 protein in mouse skeletal muscle, while aging decreased the BAX/Bcl-2 ratio, LC3I and BAX protein in mouse skeletal muscle without effects of lifelong exercise training. In humans, aging was associated with reduced PGC-1α mRNA as well as decreased p62 and p21 protein in skeletal muscle, while lifelong exercise training increased BNIP3 protein and decreased p53 mRNA. In conclusion, there was a divergent regulation of autophagy and apoptosis in mouse muscle with aging and lifelong exercise training, whereas healthy aged human skeletal muscle seemed rather robust to changes in apoptosis, autophagy and mitophagy markers compared with mouse muscle at the investigated age.

OriginalsprogEngelsk
TidsskriftExperimental Gerontology
Vol/bind111
Sider (fra-til)141-153
Antal sider13
ISSN0531-5565
DOI
StatusUdgivet - 1 okt. 2018

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