Skeletal muscle transcriptome in healthy aging

Robert A Tumasian,Alexey Lyashkov,Chee W Chia,Ranjan Sen,Jun Ding,Mary Kaileh,Linda M Zukley,Gautam Kundu,Luigi Ferrucci,William H Wood,Myriam Gorospe,Marta Gonzalez-Freire,Ceereena Ubaida-Mohien,Yulan Piao,Jen-Hao Yang,Christopher Coletta,Abhinav Harish,Supriyo De

doi:10.1038/s41467-021-22168-2

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.

Highlights

Age-associated changes in gene expression in skeletal muscle of healthy individuals reflect accumulation of damage and compensatory adaptations to preserve tissue integrity
Skeletal muscle biopsies were obtained from 53 very healthy GESTALT participants (22–83 years, median = 52 years), who were defined as very healthy based on strict inclusion criteria developed by the Clinical Research Unit of the National Institute on Aging[8]
We used RNA-seq data obtained from muscle biopsies collected from a group of individuals dispersed over a wide age range, who were established to be very healthy based on a strict enrollment criteria to explore transcriptomic changes that occur in healthy aging

Summary

Introduction

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. To overcome some of these limitations, and to replicate and complement information collected in previous studies, we performed an RNA-sequencing (RNA-seq) analysis from skeletal muscle biopsies gathered from 53 healthy individuals of ages ranging from 22 to 83 years old. We postulate that imbalances in these same mechanisms and compensatory strategies are likely to cause debilitating pathologies of aging muscle, including frailty and sarcopenia

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Conclusion