Translational signaling responses preceding resistance training-mediated myofiber hypertrophy in young and old humans

Abstract

While skeletal muscle protein accretion during resistance training (RT)-mediated myofiber hypertrophy is thought to result from upregulated translation initiation signaling, this concept is based on responses to a single bout of unaccustomed resistance exercise (RE) with no measure of hypertrophy across RT. Further, aging appears to affect acute responses to RE, but whether age differences in responsiveness persist during RT leading to impaired RT adaptation is unclear. We therefore tested whether muscle protein fractional synthesis rate (FSR) and Akt/mammalian target of rapamycin (mTOR) signaling in response to unaccustomed RE differed in old vs. young adults, and whether age differences in acute responsiveness were associated with differences in muscle hypertrophy after 16 wk of RT. Fifteen old and 21 young adult subjects completed the 16-wk study. The phosphorylation states of Akt, S6K1, ribosomal protein S6 (RPS6), eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1), eIF4E, and eIF4G were all elevated (23-199%) 24 h after a bout of unaccustomed RE. A concomitant 62% increase in FSR was found in a subset (6 old, 8 young). Age x time interaction was found only for RPS6 phosphorylation (+335% in old subjects only), while there was an interaction trend (P = 0.084) for FSR (+96% in young subjects only). After 16 wk of RT, gains in muscle mass, type II myofiber size, and voluntary strength were similar in young and old subjects. In conclusion, at the level of translational signaling, we found no evidence of impaired responsiveness among older adults, and for the first time, we show that changes in translational signaling after unaccustomed RE were associated with substantial muscle protein accretion (hypertrophy) during continued RT.

Fig. 1.

Effects of an unaccustomed resistance exercise bout on phosphorylation of Akt (A), S6K1 auto-inhibitory domain (T421/S424) (B), and ribosomal protein S6 (RPS6) (C) 24 h after exercise (Post) in young and old subjects. D: representative immunoblots. Bars are means ± SE. Significant main effects and interaction (Intrxn) terms of each age × time ANOVA are shown in A–C. *Post different from before exercise (Pre) within group as determined post hoc by Tukey's honest significant difference (HSD) test, P < 0.05. AU, arbitrary units.

Fig. 2.

Effects of an unaccustomed resistance exercise bout on phosphorylation of eukaryotic initiation factor 4E (eIF4E) binding protein (4EBP1) (A), eIF4E (B), and eIF4G (C) 24 h after exercise in young and old subjects. D: representative immunoblots. Bars are means ± SE. Significant main effects of each age × time ANOVA are shown in A–C. *Post different from Pre within group as determined post hoc by Tukey's HSD test, P < 0.05.

Fig. 3.

Effects of an unaccustomed resistance exercise bout on the fractional synthesis rate (FSR) of mixed muscle protein 24 h after exercise in young and old subjects. Bars are mean ± SE. Results of the age × time ANOVA are shown. *Post different from Pre within group as determined post hoc by Tukey's HSD test, P < 0.05.

Fig. 4.

Effects of a 16-wk resistance training program on type II myofiber cross-sectional area (CSA) (A) and distribution of type IIa and type IIx myofibers (B) in young and old subjects. Bars are means ± SE. Results of each age × time ANOVA are shown in A and B. *Post different from Pre within group as determined post hoc by Tukey's HSD test, P < 0.05.