|Genetic variation in ALDH4A1 is associated with muscle health over the lifespan and across species.
|Year of Publication
|Villa, O, Stuhr, NL, Yen, C-A, Crimmins, EM, Arpawong, TEm, Curran, SP
|C. elegans, evolutionary biology, Genetics, Genomics
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.
|PubMed Central ID
|R01 AG058610 / AG / NIA NIH HHS / United States
RF1 AG063947 / AG / NIA NIH HHS / United States
T32 AG052374 / AG / NIA NIH HHS / United States
T32 GM118289 / GM / NIGMS NIH HHS / United States
P30 AG068345 / AG / NIA NIH HHS / United States