@article {Villa2021.09.08.459547,
	title = {Genetic variation in ALDH4A1 predicts muscle health over the lifespan and across species},
	journal = {Elife},
	volume = {11},
	year = {2022},
	abstract = {Environmental stress can negatively impact organismal aging, however, the long-term impact of endogenously derived reactive oxygen species from normal cellular metabolism remains less clear. Here we define the evolutionarily conserved mitochondrial enzyme ALH-6/ALDH4A1 as a biomarker for age-related changes in muscle health by combining C. elegans genetics and a gene-wide association study (GeneWAS) from aged human participants of the US Health and Retirement Study (HRS)1{\textendash}4. In a screen for mutations that activate SKN-1-dependent oxidative stress responses in the muscle of C. elegans5{\textendash}7, we identified 96 independent genetic mutants harboring loss-of-function alleles of alh-6, exclusively. These genetic mutations map across the ALH-6 polypeptide, which lead to age-dependent loss of muscle health. Intriguingly, genetic variants in ALDH4A1 differentially impact age-related muscle function in humans. Taken together, our work uncovers mitochondrial alh-6/ALDH4A1 as a critical component of normal muscle aging across species and a predictive biomarker for muscle health over the lifespan.Competing Interest StatementThe authors have declared no competing interest.},
	keywords = {Genetic Variation, muscle health},
	doi = {10.7554/eLife.74308},
	author = {Villa, Osvaldo and Stuhr, Nicole L. and Yen, Chia-An and Eileen M. Crimmins and Thalida E. Arpawong and Curran, Sean P.}
}
