The Effects of Aging on AMPK Subunit Expression and Complex Formation

Abstract

AMP‐activated protein kinase (AMPK) is an important energy sensor in skeletal muscle. Many of the processes it regulates have been shown to be disrupted with aging. AMPK functions as heterotrimeric complex. The purpose of this study was to determine whether changes in the subunit composition of AMPK occur in aged skeletal muscle.. We studied gastrocnemius muscles from young adult (8 mo) and old (30 mo) male Fischer344 x Brown Norway F1 hybrid rats (n = 7–8/group). Immunoprecipitation (IP) of the catalytic AMPK α1 and α2 isoforms was followed by detection of associated β1, β2 and γ3 subunits by immunoblot. Protein levels for the β and γ isoforms were normalized to the corresponding α subunit with which they were immunoprecipitated. There was a 128% increase (p < 0.05) in the immunoprecipitated α1 subunit with age, accompanied by a 36% decrease in α2. There was a 59% decrease in β1 associated with α1 with age. No significant changes in β2 associated with α1, or in β1 or β2 associated with α2 were noted. AMPK γ3 association with α1 was decreased by 93% and with α2 by 83% with age. In conclusion, aging leads to a switch in AMPK subunit content and heterotrimer composition. Funding: NIAMSD Grant AR‐51928.