Reduced Training Frequency Improves Muscle Adaptation and PI3K‐AKT Signaling Following Resistance‐Type Training in an Aging Model
Authors: Naimo Marshall , Ensey James , Rader Erik , Baker Brent 
Published: June 2021

Previously, our lab has shown that modifying the frequency of resistance‐type training using stretch‐shortening contractions (SSCs) from 3 to 2 days/wk attenuates age‐dependent mal adaptation and restores muscle quality and biochemistry to a younger phenotype. PI3K‐AKT signaling is a well‐known regulator of muscle hypertrophy and decreases with age; however, it is unknown if altering training frequency can improve this response in aged muscle.PURPOSETo quantify muscle performance, morphology, and PI3K‐AKT pathway gene expression in old versus young skeletal muscle following 3 or 2 days/wk training.METHODSTibialis anterior (TA) muscles of young (3 mo) and old (30 mo) male Fischer 344 x Brown Norway rats exposed to 80 SSCs for 3 or 2 days/wk for 1 month were harvested 72 h after the last session. Total protein was quantified via BCA Protein Assay (Pierce™) and gene expression was quantified via RT2 Profiler Arrays. TA sections were stained for β‐dystroglycan and DAPI for myofiber morphology and myonuclear nuclear domain (MND) analyses. Significance was set at p<0.05.RESULTSYoung rats adapted to 3 and 2×/wk via significantly higher negative work from following training (387±15 to 484±26 N & 395±20 to 489±30, respectively)whereas old rats exposed 3×/wk had significantly decreased negative work (343±20 to 277±29 N); old 2×/wk trended towards improved negative work following training(328±7 to 392±31 N; p=0.07). For positive work, only old 3×/wk had significantly decreased performance following training (240 ± 21 to 174 ± 24 N); both young 3×/wk (317±26 N) and 2×/wk (323±22 N) as well as old 2×/wk (241±23 N) had higher positive work than old 3×/wk. Chi‐square analysis showed a significant shift in distribution towards greater fiber area and higher MND in both young and old 2×/wk, whereas old 3×/wk had no changes. Significant increases were noted for % central nucleated fibers (CNF) in young 2×/wk relative to non‐loaded control (NLC) muscle and young 3×/wk muscle (14.3±2.2 vs. 7.3±1.2 vs. 8.3±2.2 %). Old 2×/wk had a significantly higher % CNF compared to old 3×/wk (15.1±1.7 vs. 4.3±1.4 %). Muscle protein was significantly increased in exercised relative to NLC muscle only in old 2×/wk [6.0±0.5 vs. 7.8±0.4 μg/mg wet weight (ww)], with no change in old 3×/wk (6.0±0.5 vs. 6.3±0.2 μg/mg ww). Additionally, muscle protein was significantly higher in old 2×/wk compared to old 3×/wk. Finally, young rats exposed to 3 and 2×/wk training differentially (p<0.05) expressed 19 and 30 PI3K‐AKT pathway genes, respectively; old 3×/wk only expressed 2 genes. Old 2×/wk differentially (p<0.05) expressed 8 PI3K‐AKT genes; interestingly, Fos and Jun, known regulators of satellite cell activation, were upregulated(Fos, 6.3 fold; Jun, 1.6 fold).CONCLUSIONSReduced training frequency improves the molecular milieu of aged muscle through enhanced PI3K‐AKT signaling and an augmented muscle protein response that was more similar to younger muscle. A heightened central nuclei response possibly via higher levels of Fos and Jun could explain the restoration of adaptation owing to improved functional outcomes.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.