Adaptability to eccentric exercise training is diminished with age in female mice

Abstract

The ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the 5th bout to identify common and differentially regulated genes. Young muscle exhibited a robust ability to adapt, increasing isometric torque 20-36%, while isometric torque of older muscle decreased up to 18%; adaptive potential was less in older muscle compared to young muscle (p≤0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles.

Age-related blunting of serial sarcomerogenesis and mechanical adaptations following 4 weeks of maximal eccentric resistance training

“…Old rats, conversely, had a gradual drop in maximum torque throughout the entire training period, which was accelerated by adding faster eccentric contractions (which are typically more damage-inducing (44,45)) starting at day 7. A recent study comparing old and young mice observed similar findings, with young mice becoming 20-36% stronger but old mice becoming 18% weaker following 5 weeks of high-intensity eccentric training 1 day/week (97). One explanation in the present study may be the lower pre-training SSN in old rats compared to young.…”

“…To that point, Rahman et al (102) observed that impaired ECM remodelling limited the regenerative response following damage to the tibialis anterior induced by cardiotoxin in old compared to young mice. Furthermore, Baumann et al (97) compared gene profiles of young and old mice following 5 weeks of eccentric training, and found that while young and old mice both exhibited upregulation of genes associated with sarcomere organization and assembly, only old mice exhibited upregulation of genes associated with ECM remodelling, likely indicative of fibrosis. This remodeling of the local connective tissue environment in old may blunt the ability for a mechanical signal to be transduced into a biochemical response (8,107), limiting serial sarcomerogenesis.…”