Potential Mechanisms Of Inflammation-induced Attenuated Muscle Hypertrophy Following 3-d/wk High-intensity Resistance Training Among Aged Individuals

Abstract

PURPOSE: Aging related loss in muscle mass (sarcopenia) is major contributor to functional disability and all-cause mortality. Resistance exercise training (RT) is an established treatment for age-related losses in muscle mass, strength, and power. However, we have previously found that 3 d/wk of heavy RT in older adults may blunt the hypertrophic response to progressive resistance training. We postulate that this effect is mediated by skeletal muscle inflammation, indicated by heightened expression of TNFR1 and TWEAK-R. Typically, acute exercise induced inflammation is beneficial to muscle hypertrophy, and this regimen has been shown to be well tolerated by young adults. However, impaired exercise tolerance and adaptability sometimes demonstrated in older adults may be mediated by increased basal muscle inflammatory burden, coupled with an exaggerated inflammatory response to muscle loading. We hypothesize that this phenomenon in the aging cohort may impair hypertrophic responses to RT if intensive loading occurs too frequently (i.e. 3 d/wk). METHODS: This study builds on a previous clinical trial conducted by our lab (NCT02442479), analyzing muscle hypertrophy in a four-arm, randomized dose-response trial to determine optimal exercise treatment for aging individuals (60-75 y). For this follow-up molecular analysis, we analyzed two of the groups of interest that underwent either 3 d/wk mixed model consisting of two days high-intensity training days separated by one low-intensity, concentric only day (HLH, n = 18) or 3 d/wk high-intensity training regimen (HHH, n = 18). Skeletal muscle biopsies were collected before and after 35 weeks of training in either HLH or HHH. Muscle and serum-derived miRNA-Seq is underway to identify potentially novel regulators of muscle hypertrophy and inflammation, accompanied by targeted muscle analysis of key inflammatory pathways (e.g., TNF/TWEAK-NFkB, IL-6-STAT3). RESULTS AND CONCLUSION: We expect that results from this study will advance our understanding of the role of inflammation in blunting muscle hypertrophy in aging adults, including a better understanding of both dose optimization and inter-individual response heterogeneity. Supported by T32HD071866 and UAB Center for Exercise Medicine.