The genomics of exceptional longevity in rockfishes refine genetic foundations of human lifespan variation
Year: 2021
Type: preprint
Abstract: Longevity is a defining, heritable trait that varies dramatically between species. To resolve the genetic regulation of this trait, we have mined genomic variation in rockfishes, ranging in longevity from 11 to over 205 years. Shifts in rockfish longevity occurred multiple times independently, and in a short evolutionary time frame, thus empowering convergence analyses. Our analyses reveal a common network of genes under convergent restricted evolution in long-lived lineages, encompassing established aging regulators such as insulin-signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a novel pathway modulating longevity. Further, these genes were used to refine human longevity GWAS, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with the 99th percentile of human longevity, independently validating its importance and conservation. This evolutionary intersection highlights a novel, conserved genetic architecture that associates with the evolution of longevity across vertebrates and provides actionable targets for research into lifespan and healthspan modulation.
Source: Research Square
Institutions: Boston Children's Hospital, Harvard University, University of Cologne, Leiden University Medical Center, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Max Planck Institute for Biology of Ageing, Northeastern University, Boston University, Framingham Heart Study, Bar-Ilan University, Hebrew SeniorLife
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4200483468