| The age-related decline in muscle mass (sarcopenia) can be attenuated but not completely prevented by resistance exercise. This phenomenon may be attributable in part to diminished overload-induced protein synthesis rates in aged skeletal muscle. While the mechanisms underlying this effect are unclear, potential contributing factors may include age-related differences in the activation of translational signaling through the mammalian target of rapamycin (mTOR) and its direct and indirect downstream targets including the 70-kDa ribosomal protein S6 kinase (p70S6k) and eukaryotic elongation factor-2 (eEF2). Translational signaling is rapidly but transiently elevated following resistance exercise, while protein synthesis rates are not elevated until several hours later. It has been postulated that this early event may therefore be an important priming step for the protein synthesis response, but this hypothesis had not previously been tested. Thus, we first explored this possibility in young adult (Y; 8mo.) male Fischer344 x Brown Norway (FBN) rats by inhibiting early post-resistance exercise [achieved via high frequency electrical stimulation (HFES)] translational signaling via pharmacological activation of 5'-AMP-activated protein kinase (AMPK, a known inhibitor of translational signaling and protein synthesis) with 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR). As hypothesized, this inhibition prevented the exercise-associated increase in protein synthesis rate seen 24 hours later in saline-treated control animals. In a second experiment, in vivo AMPK activity was elevated in skeletal muscle of old (O; 30mo.) but not of Y FBN rats following HFES in both lengthening and shortening skeletal muscle. However, in contrast to the findings with pharmacological AMPK activation, the physiological AMPK response to resistance exercise in O skeletal muscle did not consistently coincide with an apparent inhibitory effect on early post-exercise translational signaling. Interestingly, the protein synthesis response at 24 hours was attenuated with age, but for reasons currently unclear, this only occurred in shortening but not in lengthening skeletal muscle. Taken together, these results suggest that the early post-resistance exercise elevation in translational signaling may be necessary for the sustained increase in protein synthesis rate seen 24 hours later. However, the normal physiological AMPK response to this HFES protocol in O animals was not consistently associated with discernibly less translational signaling or protein synthesis rates vs. their Y counterparts. |
