Skeletal muscle transcriptome in healthy aging

Robert A. Tumasian, Abhinav Harish, Gautam Kundu, Jen-Hao Yang, Ceereena Ubaida-Mohien, Marta Gonzalez-Freire, Mary Kaileh, Linda M. Zukley, Chee W. Chia, Alexey Lyashkov, William H. Wood, Yulan Piao, Christopher Coletta, Jun Ding, Myriam Gorospe, Ranjan Sen, Supriyo De and Luigi Ferrucci ()
Additional contact information
Robert A. Tumasian: National Institute on Aging–Intramural Research Program, National Institutes of Health
Abhinav Harish: National Institute on Aging–Intramural Research Program, National Institutes of Health
Gautam Kundu: National Institute on Aging–Intramural Research Program, National Institutes of Health
Jen-Hao Yang: National Institute on Aging–Intramural Research Program, National Institutes of Health
Ceereena Ubaida-Mohien: National Institute on Aging–Intramural Research Program, National Institutes of Health
Marta Gonzalez-Freire: National Institute on Aging–Intramural Research Program, National Institutes of Health
Mary Kaileh: National Institute on Aging–Intramural Research Program, National Institutes of Health
Linda M. Zukley: National Institute on Aging–Intramural Research Program, National Institutes of Health
Chee W. Chia: National Institute on Aging–Intramural Research Program, National Institutes of Health
Alexey Lyashkov: National Institute on Aging–Intramural Research Program, National Institutes of Health
William H. Wood: National Institute on Aging–Intramural Research Program, National Institutes of Health
Yulan Piao: National Institute on Aging–Intramural Research Program, National Institutes of Health
Christopher Coletta: National Institute on Aging–Intramural Research Program, National Institutes of Health
Jun Ding: National Institute on Aging–Intramural Research Program, National Institutes of Health
Myriam Gorospe: National Institute on Aging–Intramural Research Program, National Institutes of Health
Ranjan Sen: National Institute on Aging–Intramural Research Program, National Institutes of Health
Supriyo De: National Institute on Aging–Intramural Research Program, National Institutes of Health
Luigi Ferrucci: National Institute on Aging–Intramural Research Program, National Institutes of Health

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Age-associated changes in gene expression in skeletal muscle of healthy individuals reflect accumulation of damage and compensatory adaptations to preserve tissue integrity. To characterize these changes, RNA was extracted and sequenced from muscle biopsies collected from 53 healthy individuals (22–83 years old) of the GESTALT study of the National Institute on Aging–NIH. Expression levels of 57,205 protein-coding and non-coding RNAs were studied as a function of aging by linear and negative binomial regression models. From both models, 1134 RNAs changed significantly with age. The most differentially abundant mRNAs encoded proteins implicated in several age-related processes, including cellular senescence, insulin signaling, and myogenesis. Specific mRNA isoforms that changed significantly with age in skeletal muscle were enriched for proteins involved in oxidative phosphorylation and adipogenesis. Our study establishes a detailed framework of the global transcriptome and mRNA isoforms that govern muscle damage and homeostasis with age.

Date: 2021
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DOI: 10.1038/s41467-021-22168-2

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