Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults

Abstract

This investigation examined the effects of acute resistance exercise (RE), progressive resistance training (PRT), and age on the human skeletal muscle Transcriptome. Two cohorts of young and old adults [study A: 24 yr, 84 yr (n = 28); study B: 25 yr, 78 yr (n = 36)] were studied. Vastus lateralis biopsies were obtained pre- and 4 h post-RE in conjunction with the 1st and 36th (last) training session as part of a 12-wk PRT program in study A, whereas biopsies were obtained in the basal untrained state in study B. Additionally, the muscle fiber type specific (MHC I and MHC IIa) Transcriptome response to RE was examined in a subset of young and old women from study A. Transcriptome profiling was performed using HG U133 Plus 2.0 Arrays. The main findings were 1) there were 661 genes affected by RE during the 1st and 36th training bout that correlated with gains in muscle size and strength with PRT (termed the Transcriptome signature of resistance exercise adaptations); 2) the RE gene response was most pronounced in fast-twitch (MHC IIa) muscle fibers and provided additional insight into the skeletal muscle biology affected by RE; 3) skeletal muscle of young adults is more responsive to RE at the gene level compared with old adults and age also affected basal level skeletal muscle gene expression. These skeletal muscle Transcriptome findings provide further insight into the molecular basis of sarcopenia and the impact of resistance exercise at the mixed muscle and fiber type specific level.

Fig. 1.

Study design for the analysis of effects of resistance exercise (RE) and progressive resistance training (PRT) on vastus lateralis gene expression. Young and old adults of study A performed an acute bout of RE (3 × 10 repetitions at 70–75% of 1 repetition maximum) in the untrained and trained state. Muscle biopsies were collected pre and 4 h after the RE bout. In young and old women myosin heavy chain (MHC) I and IIa muscle fibers (pools of 20 fibers) were isolated and analyzed for gene expression response to RE.

Fig. 2.

Transcriptome signature of RE adaptations. A correlation analysis was conducted, examining each participant's (28 subjects, study A) gene response to resistance exercise in the untrained (1st training session) and trained (36th training session) state and the muscle size (CSA) and strength (1-RM) adaptations in each participant after 12 wk of training. If a gene was present in all 4 lists, it qualified for the Transcriptome signature of resistance exercise adaptations.

Fig. 3.

Correlation illustration of 2 genes from the Transcriptome signature of resistance exercise adaptations. Top half: tumor necrosis factor receptor superfamily, member 12A (TNFRSF12A), also known as both fibroblast growth factor inducible gene 14 (Fn14) and the TWEAK receptor. Bottom half: NF-κB inhibitor alpha (NFKBIA), also known as Iκβα. Graphs show the responsiveness of these 2 genes within all the subjects during the 1st and 36th RE bout and how the gene response correlated with 1-RM and CSA adaptations after 12 wk of training. ○, pre (basal) value for the gene expression signal and 1-RM or CSA. ▴, 4 h post-RE gene expression signal and the 1-RM and CSA of the subject after 12 wk of training.

Fig. 4.

Fiber type specific microarray analysis revealed fast-twitch MHC IIa muscle fibers of young women are responsive to acute RE in the untrained state with 463 genes altering expression, whereas only 63 genes responded among the MHC IIa muscle fibers of the old women (top). When the fiber type specific gene response of the young and old women is coupled with the muscle fiber CSA adaptations after PRT (bottom) in those women (38), the data support that a substantial gene response after RE is needed to acquire greater physiological adaptations over time. *P < 0.05 from pre- to posttraining.