Genetic Variation in is Associated with Muscle Health over the Lifespan and Across Species

Overview

Journal Elife

Specialty Biology

Date 2022 Apr 26

PMID 35470798

Authors

Osvaldo Villa

Nicole L Stuhr

Chia-An Yen

Eileen M Crimmins

Thalida Em Arpawong

Sean P Curran

Affiliations

Soon will be listed here.

Abstract

The influence of genetic variation on the aging process, including the incidence and severity of age-related diseases, is complex. Here, we define the evolutionarily conserved mitochondrial enzyme ALH-6/ALDH4A1 as a predictive biomarker for age-related changes in muscle health by combining genetics and a gene-wide association scanning (GeneWAS) from older human participants of the US Health and Retirement Study (HRS). In a screen for mutations that activate oxidative stress responses, specifically in the muscle of , we identified 96 independent genetic mutants harboring loss-of-function alleles of , exclusively. Each of these genetic mutations mapped to the ALH-6 polypeptide and led to the age-dependent loss of muscle health. Intriguingly, genetic variants in show associations with age-related muscle-related function in humans. Taken together, our work uncovers mitochondrial as a critical component to impact normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.

Citing Articles

Turner C, Stuhr N, Ramos C, Van Camp B, Curran S Proc Natl Acad Sci U S A. 2023; 120(52):e2308565120.

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