Effect Of Resistance Exercise Training On Anabolic Resistance To Amino Acids In Healthy Older Adults

Abstract

Aging attenuates the contraction-induced stimulation of muscle protein synthesis (MPS). This phenomenon is termed “anabolic resistance”, and may contribute to the slow loss of muscle mass with advancing age (sarcopenia). Some studies also reported anabolic resistance to amino acid/protein intake with aging. However, this notion has not been firmly established. Acute bouts of exercise can improve the ability of amino acids to stimulate MPS by activating mechanistic target of rapamycin complex 1 (mTORC1) signaling and translation initiation, but it is not known whether chronic exercise training may improve muscle sensitivity to amino acid availability. PURPOSE: The aim of this study was to determine if healthy older adults exhibit muscle anabolic resistance to essential amino acid intake (EAA), and whether resistance exercise training (RET) improves the muscle sensitivity to EAA. METHODS: To test our hypothesis 19 healthy older adults (65-80 years old) underwent a 12-week progressive resistance exercise training program (RET). Before and after training we measured muscle mass and strength, and performed stable isotope infusion experiments with muscle biopsies to determine MPS and markers of amino acid sensing in the basal state and in response to EAA ingestion. RESULTS: RET increased muscle strength (+15%), lean mass (+2%), and muscle cross sectional area (+17%) in healthy older adults (P<0.05). MPS and mTORC1 signaling (i.e., phosphorylation status of 4E-BP1, S6K1, and rpS6) increased following EAA ingestion (P<0.05). Basal MPS increased by 28% after RET (P<0.05). However, the amplitude of the response of MPS and mTORC1 signaling to EAA ingestion did not differ from pre-training values (P>0.05). CONCLUSION: Aging does not inhibit the EAA-stimulation of muscle mTORC1 signaling and MPS. In addition, RET did not increase the sensitivity of muscle to amino acids. Our data indicate that anabolic resistance to amino acids is not a significant problem in healthy older adults. We suggest that future work in conditions associated with more pronounced muscle wasting is necessary to determine whether exercise training can improve muscle sensitivity to amino acids or protein. Supported by NIH/NIA R56 AG051267, P30 AG024832, NIH/NCATS UL1 TR001439.