Skeletal Muscle Anabolic and Catabolic Signaling Following Acute Resistance Exercise in Young and Older Adults

Several recent studies have noted a blunted muscle protein synthetic response following an acute bout of resistance exercise (RE) in older individuals. Much less is known regarding the effect of age on the muscle protein breakdown response to RE. The effect of age on the regulation of muscle anabolic and catabolic signaling pathways following RE is not well characterized. We hypothesized that aging would be associated with a reduced overall muscle protein anabolic response. PURPOSE: To determine whether a differential aging response exists in skeletal muscle protein synthesis and breakdown signaling during a 24h time-course following a bout of RE. METHODS: 8 young (age=27±2 yrs) and 8 older subjects (age=70±2 yrs) performed a bout of leg-extensions at 70% 1RM. Muscle biopsies were obtained from the vastus lateralis at baseline and at 3, 6 and 24h post-exercise. Intracellular signaling was assessed with immunoblotting methods. RESULTS: We observed a significant increase in the phosphorylation of S6K1 (Thr389) (0.14+0.02 vs 0.26+0.02 AU) and rpS6 (Ser240/244) (0.04+0.0 vs 0.07+0.0) at all post-exercise time points in the young (P<0.05), with no changes in the older subjects (0.14+.01 vs 0.13+.01, S6K1) (0.05+0.0 vs 0.05+0.0, rpS6) (P>0.05). Older subjects also had a reduced S6K1/rpS6 phosphorylation compared to the young at 6 and 24h post-exercise (P<0.05). Our preliminary data for catabolic signaling shows that phospho-Akt (Thr308), an upstream effector of E3 ubiquitin ligases, increased at 3 and 6h post-exercise in the young (P<0.05) with no changes in the older subjects (P>0.05). Akt phosphorylation was also higher in young compared to old at 6 and 24h post-exercise (P<0.05). Total LC3B protein, indicative of autophagy induction, decreased at both 6 and 24h post-exercise in the young subjects (1.07+0.13 vs 0.59+0.06) (P<0.05) and decreased at all post-exercise time points in the old (1.09+0.12 vs 0.60+0.09) (P<0.05). CONCLUSIONS: We conclude that aging is associated with a dysregulation of anabolic and catabolic signaling following RE which may contribute to the blunted muscle protein anabolic response to RE in older adults. Supported by NIH/NIAMS R01AR049877, P30AG024832 and T32HD07539.