Network Analysis Identifies Circulating MicroRNA Associated With Muscle Mass Gains In Resistance Trained Older Adults

Abstract

Purpose: Age related muscle loss (sarcopenia) is a major contributor to functional disability and all-cause mortality. Rescuing muscle mass in older adults has been most effective with resistance exercise training (RT). We have previously demonstrated that 3d/wk of heavy RT in older adults may blunt the hypertrophic response to progressive resistance training. We postulate that this effect may be mediated by epigenetic factors, such as, microRNA (miRNA), resulting in impaired muscle mass growth. We hypothesize that insufficient recovery time may contribute to attenuated hypertrophic responses to RT if intensive loading occurs too frequently (i.e. 3 d/wk). The present study is a follow up molecular analysis of two RT cohorts from our previous clinical trial (NCT02442479) in which optimal exercise dose for aging individuals (60-75y) was determined from four RT cohorts. That trial determined that a dose consisting of 2 d/wk high-intensity RT separated by a low-intensity, concentric only day (HLH) was superior to 3 d/wk high-intensity RT (HHH) for thigh lean mass gains. Methods: The present study sequenced circulating miRNA from serum exosomes pre- and post- 35 weeks of RT in 19 individuals that underwent either HLH or HHH RT. Subsequent analysis was performed via weighted gene co-expression network analysis (WGCNA) to identify modules of eigengenes with miRNA membership correlated with treatment and thigh lean mass gains. Network analysis and visualization of these modules were performed. Results and Conclusion: WGCNA identified modules correlated with treatment (p = 0.03, p = 0.05) and with thigh lean mass gains (p = 0.006 and p = 0.01) at the final time point (35wk). Pathway analysis provides insight into regulated pathways that may be attributed RT frequency and subsequent magnitude of thigh lean mass hypertrophy between the two treatment groups. Altogether, this analysis reports on a molecular exercise response in aging individuals that may better inform exercise dose optimization, as well as, deepen our understanding of inter-individual response heterogeneity. Supported by T32HD071866 and P2CHD086851.