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

1 Medical Scientist Training Program and ; Departments of 2 Physiology and Biophysics and ; 3 Surgery, University of Alabama at Birmingham; and ; 4 Geriatric Research, Education, and Clinical Center, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama; and ; 5 Center for Translational Research in Aging and Longevity and Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas Submitted 15 September 2008 ; accepted in final form 6 July 2009 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. translation initiation; protein synthesis; muscle fiber; aging Address for reprint requests and other correspondence: M. M. Bamman, Core Muscle Research Laboratory, UAB Dept. of Physiology and Biophysics, 966 McCallum Basic Health Sc