%0 Journal Article %J Elife %D 2022 %T Genetic variation in ALDH4A1 is associated with muscle health over the lifespan and across species. %A Villa, Osvaldo %A Stuhr, Nicole L %A Yen, Chia-An %A Eileen M. Crimmins %A Arpawong, Thalida Em %A Curran, Sean P %K C. elegans %K evolutionary biology %K Genetics %K Genomics %X

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.

%B Elife %V 11 %P e74308 %G eng %R 10.7554/eLife.74308