G.P.206: Consequences of dietary challenge and aging on macroautophagy in Myf5+ cells and muscle

Abstract

Macroautophagy (MA) maintains protein and organelle quality control and energy balance, and it has also been shown to play regulatory and developmental roles in various tissues. In differentiated skeletal muscle, inhibition of MA leads to degenerative muscle loss and decreases force production. Myogenic factor 5 positive (Myf5 + ) progenitor cells give rise to skeletal muscle and satellite cells, and accordingly, blocking MA in mouse Myf5 + cells using a conditional autophagy gene 7 (Atg7) knockout decreases myofiber size, perturbs muscle Akt signaling and promotes glucose intolerance. These results suggest that MA in Myf5 + is required for early muscle development, and in control of glucose homeostasis. Aging and obesity associate with both reduced MA and sarcopenia, thus raising the possibility that their effects on muscle mass could be in part due to compromised MA in Myf5 + cells. We hypothesized that aging and/or obesity impair MA activity in Myf5 + cells, which in turn contributes to loss of muscle mass through impaired muscle growth and regeneration. To study the effects of aging and dietary challenge, young mice were compared to 22-month-old aged mice, and to mice fed a high-fat diet (HFD) providing 60% by energy in fat. Expression of Atg genes and ATG protein levels in muscle and Myf5 + cells was analyzed by RT-PCR and Western blotting, respectively, while autophagic activity was determined by flux assays. We have previously observed decreased MA with obesity and age in liver and hypothalamic neurons, respectively. Here we present a conceptual framework to consider that compromised MA during obesity and aging may contribute to decreased muscle mass with age. Understanding how MA decreases with age may provide therapeutic strategies against sarcopenia and metabolic syndrome of aging.