Cluster analysis to reveal differentially expressed myogenic genes during load‐mediated myofiber growth in humans

Abstract

We have identified a number of genes up-regulated by acute resistance loading; however, their role in myofiber hypertrophy has not been resolved. We therefore determined which “myogenic” genes were differentially expressed during growth in muscles realizing robust hypertrophy vs. those more resistant. After 16 wk of resistance training (RT), 66 humans were statistically clustered based on changes in mean fiber area (MFA, μm2) as non-responders (NR, n=17), modest responders (MR, +1111 μm2, n=32), and extreme responders (XR, +2475 μm2, n=17). Target mRNAs were assessed in 3 muscle biopsies (baseline and 24 h after first and last bouts). MGF increased (P<0.05) 62% in MR and 116% in XR with no change in NR. Myogenin also rose (P<0.01) in MR (49%) and XR (100%) with no change in NR. All 3 clusters (P<0.05) increased IGF-IEa, with the largest change in XR (174%). Elevations in MyoD and myf-5 (P<0.05) did not differ by cluster. Myf-6 did not change. Among the factors up-regulated during RT, only MGF and myogenin were differentially increased across clusters. Failure to increase these 2 targets in NR suggests these transcripts (and their protein products) play requisite roles during load-mediated myofiber hypertrophy. As the active IGF-I peptide is the same for MGF and IGF-IEa, mechanotransduction mechanisms that enhance local levels of this growth factor appear more effective in responders. Support: R01 AG017896 and VA Merit.