Skeletal muscle autophagy and protein breakdown following resistance exercise are similar in younger and older adults

Abstract

Background: The loss of skeletal muscle mass and strength during aging, sarcopenia, increases the risk for falls and dependency. Resistance exercise (RE) training is effective at improving muscle mass and strength in older adults; however, aging is associated with reduced training-induced hypertrophy. Recent research has illustrated an impaired muscle protein synthetic response following an acute bout of RE in older adults but much less is known regarding the effect of acute RE on muscle protein breakdown (MPB). We hypothesize that the ubiquitin proteasome system and the autophagosomal-lysosomal system may regulate the overall rate of MPB during postexercise recovery.

Methods: Muscle biopsies of the vastus lateralis were sampled from 16 older (age = 70±2 years) and 16 younger (age = 27±2 years) participants at baseline and at 3, 6, and 24 hours following an acute bout of RE. In conjunction with stable isotopic techniques to measure MPB, we utilized immunoblotting and RT-PCR to examine protein and mRNA expression for key signaling molecules in both the ubiquitin proteasome system and the autophagosomal-lysosomal system.

Results: MuRF1 mRNA expression increased, whereas GABARAP mRNA decreased after RE in both younger and older adults (p < .05). The LC3B-II/LC3B-I protein ratio decreased in both groups after RE (p < .05), but MPB was not different 24 hour post-RE in either group (p > .05).

Conclusions: Aging does not influence skeletal MPB, autophagy, or the ubiquitin proteasome system following an acute bout of RE. Therefore, targeting the muscle protein synthesis response to exercise may hold more promise in the prevention of sarcopenia.

Figure 1.

Study design. Blood was sampled throughout the study and muscle samples were taken at the times indicated (X). Exercise was performed after the second biopsy.

Figure 6.

Representative total protein images. Representative immunoblot images from, Akt, FoxO3a, and α-tubulin.

Figure 2.

Upstream regulators of muscle protein breakdown (MPB). Data represent phosphorylation of Akt at Thr308 (A) and FoxO3a at Ser253 (B) at baseline, 3, 6, and 24 hour post-exercise. Representative immunoblot images are shown. *Significantly different from baseline (p < .05).

Figure 3.

mRNA expression of E3 ubiquitin ligases and autophagy markers. Data represent MuRF1 (A), MAFbx (B), LC3 (C), and GABARAP (D) mRNA expression between younger and older participants at baseline, 3, 6, and 24 hour post-exercise. *Significantly different from baseline (p < .05).

Figure 4.

LC3B protein expression. Data represent total protein content of LC3B-I (A), LC3B-II (B), and the LC3B-II/LC3B-I ratio (C) at baseline, 3, 6, and 24 hour post-exercise. Representative immunoblot images are shown. *Significantly different from baseline (p < .05).

Figure 5.

Regulation of autophagy induction. Data represent total protein content of Atg7 (A) and beclin-1 (B) at baseline, 3, 6, and 24 hour post-exercise. Representative immunoblot images are shown. *Significantly different from baseline (p < .05). #Significantly different from older participants (p < .05).

Figure 7.

Fractional breakdown rate (FBR) of skeletal muscle proteins. Data represent FBR of younger and older participants at baseline and 24 hour post-exercise.