Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging

Abstract

Skeletal muscle loss during aging leads to an increased risk of falls, fractures, and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia; however, the muscle protein synthesis (MPS) response to resistance exercise is less in elderly compared with young subjects. On the other hand, essential amino acids (EAA) increase MPS equally in both young and old subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion following a bout of resistance exercise would stimulate anabolic signaling and MPS similarly between young and old men. Each subject ingested 20 g of EAA 1 h following leg resistance exercise. Muscle biopsies were obtained before and 1, 3, and 6 h after exercise to measure the rate of MPS and signaling pathways that regulate translation initiation. MPS increased early in young (1-3 h postexercise) and later in old (3-6 h postexercise). At 1 h postexercise, ERK1/2 MNK1 phosphorylation increased and eIF2alpha phosphorylation decreased only in the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups at all time points, but MNK1 phosphorylation was lower at 3 h and AMP-activated protein kinase-alpha (AMPKalpha) phosphorylation was higher in old 1-3 h postexercise. We conclude that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men; however, the response is delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old muscle may be playing a role in the delayed activation of MPS. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia.

Figures

Fig. 1

Study design. Blood and muscle biopsies were taken at times indicated by arrows. Resistance exercise (Exc) began immediately after the second biopsy. Essential amino acids (EAA) were ingested immediately after the 3rd biopsy (1 h postexercise). 1RM, one-repetition maximum.

Fig. 2

A: muscle protein synthesis as expressed by the mixed muscle fractional synthesis rate (FSR) in young (n = 7) and old (n = 6) subjects at baseline and at exercise (Ex) + 1 h, 1-3 h, and 3-6 h after resistance exercise. B: average muscle protein synthesis over a 5-h period in young and old skeletal muscle after resistance exercise and essential amino acids. *Significantly different from baseline (P < 0.05). #Significantly different from old subjects at corresponding time point (P < 0.05).

Fig. 3

Data represent phosphorylation of Akt at Ser473 (young: n = 7, old: n = 6; A) and AMPKα at Thr172 (young: n = 6, old: n = 6; B) between young and old at baseline (B) and 1, 3, and 6 after resistance exercise. Representative immunoblot images are shown above. *Significantly different from baseline (P < 0.05). #Significantly different from young subjects at corresponding time point (P < 0.05).

Fig. 4

Data represent phosphorylation of mTOR at Ser2448 (young: n = 7, old: n = 6; A), S6K1 at Thr389 (young: n = 7, old: n = 6; B), 4E-BP1 at Thr37/46 (young: n = 7, old: n = 6; C), and eEF2 at Thr56 (young: n = 7, old: n = 6; D) between young and old at baseline and 1, 3, and 6 h after resistance exercise. Representative immunoblot images are shown above. *Significantly different from baseline (P < 0.05).

Fig. 5

Data represent phosphorylation of glycogen synthase kinase β (GSK3β) at Ser9 (young: n = 6, old: n = 6; A) and eukaryotic initiation factor α (eIF2α)at Ser52 (young: n = 6, old: n = 6; B) between young and old at baseline and 1, 3, and 6 h postresistance exercise. Representative immunoblot images are shown above. *Significantly different from baseline (P < 0.05). #Significantly different from old subjects at corresponding time point (P < 0.05).

Fig. 6

Data represent phosphorylation of ERK1/2 at Thr202/Tyr204 (young: n = 6, old: n = 6; A) and MAPK-interacting kinases 1 (MNK1) at Thr197 (young: n = 6, old: n = 6; B) between young and old at baseline and 1, 3, and 6 h postresistance exercise. Representative immunoblot images are shown above. *Significantly different from baseline (P < 0.05). #Significantly different from old subjects at corresponding time point (P < 0.05).