Network analysis of human muscle adaptation to aging and contraction

Etheridge, Timothy; Willis, CRG; Atherton, Philip; Ames, Ryan; Szewczyk, Nathaniel; Deane, Colleen; Kadi, Fawzi; Phillips, Bethan; Smith, Kenneth; Boereboom, Catherine; Wilkinson, Daniel; Abdulla, Haitham; Williams, John; Bukhari, Syed; Lund, Jonathan

Abstract

Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we employed a network-driven pipeline to identify putative molecular drivers of muscle aging and contraction mode responses. RNA-sequencing data was generated from young (21±1 y) and older (70±1 y) human skeletal muscle before and following acute unilateral concentric and contralateral eccentric contractions. Application of weighted gene co-expression network analysis identified 33 distinct gene clusters (‘modules’) with an expression profile regulated by aging, contraction and/or linked to muscle strength. These included two contraction ‘responsive’ modules (related to ‘cell adhesion’ and ‘transcription factor’ processes) that also correlated with the magnitude of post-exercise muscle strength decline. Module searches for ‘hub’ genes and enriched transcription factor binding sites established a refined set of candidate module-regulatory molecules (536 hub genes and 60 transcription factors) as possible contributors to muscle aging and/or contraction responses. Thus, network-driven analysis can identify new molecular candidates of functional relevance to muscle aging and contraction mode adaptations.

• Journal Article Type: Article
• Acceptance Date: Dec 24, 2019
• Online Publication Date: Jan 7, 2020
• Publication Date: Jan 15, 2020
• Deposit Date: Jan 12, 2020
• Publicly Available Date: Jan 13, 2020
• Journal: Aging
• Electronic ISSN: 1945-4589
• Publisher: Impact Journals
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• Pages: 740-755
• DOI: https://doi.org/10.18632/aging.102653
• Public URL: https://nottingham-repository.worktribe.com/output/3714217
• Publisher URL: https://www.aging-us.com/article/102653/text