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Aging Induces A Differential Muscle Transcriptome Profile Following Resistance Exercise Training

PURPOSE: Resistance exercise training (RET) in older adults produces a lesser muscle hypertrophy response as compared to young adults. We hypothesized that this anabolic resistance to exercise may be associated with a differential muscle transcriptome profile. We enrolled 10 young and 10 older men into a 12-week progressive RET program. Skeletal muscle biopsies were obtained from the vastus lateralis before and after RET. METHODS: The transcriptome profiles of skeletal muscle from both young and older adults were obtained by utilizing next-generation RNA sequencing. RESULTS: We analyzed a total of 26,486 genes (i.e., RNA transcripts) in skeletal muscle and found that 11,262 genes in young subjects and 11,830 genes in the older adults were upregulated after 12 weeks of RET. On the other hand, we observed a down-regulation of 11,079 and 11,214 genes in the young and old groups, respectively. In particular, we found that autophagy linked gene expression (e.g., ATG 12, PIK3R4, ULK 2, ULK3) and transcripts related to muscle hypertrophy (e.g., AKT, EIF2S2, GSK3b) were differentially expressed between young and older adults. Interestingly, we identified 21 genes (e.g., COL5A2, COL3A1 COL1A1) encoding extracellular matrix (ECM) and ECM-associated proteins that were significantly upregulated only in the elderly (P<0.05). CONCLUSIONS: Skeletal muscle gene expression is differentially regulated in older adults in response to RET which may contribute to anabolic resistance and reduced muscle hypertrophy with aging. Future studies will include mechanistic experiments to identify how aging alters gene expression and whether anabolic resistance can be reversed. Funding: NIH/NIA R56 AG051267