Network analysis of human muscle adaptation to aging and contraction

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 putat...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2020-01, Vol.12 (1), p.740-755
Main Authors: Willis, Craig R G, Ames, Ryan M, Deane, Colleen S, Phillips, Bethan E, Boereboom, Catherine L, Abdulla, Haitham, Bukhari, Syed S I, Lund, Jonathan N, Williams, John P, Wilkinson, Daniel J, Smith, Kenneth, Kadi, Fawzi, Szewczyk, Nathaniel J, Atherton, Philip J, Etheridge, Timothy
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Aging
candidate target discovery
Computational Biology - methods
contraction
Exercise
Female
Gene Expression Profiling
Gene Ontology
Gene Regulatory Networks
Geriatric Assessment
Humans
Male
Muscle Contraction
Muscle, Skeletal - metabolism
Muscle, Skeletal - physiopathology
network analysis
Research Paper
skeletal muscle
Transcriptome
Young Adult
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.102653