A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling

• DOI: 10.1038/s41467-021-25920-w
• Publication Date: 2021-10-12T12:05:45Z
• Authors: Hae-Eun H. Park; Wooseon Hwang; Seokjin Ham; Eunah Kim; Ozlem Altintas; Sangsoon Park; Heehwa G. Son; Yujin Lee; Dongyeop Lee; Won Do Heo; Seung-Jae V. Lee
• Keywords: Genetic screen

Abstract Insulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans , mutations the daf-2 /insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, reproduction. Whether these pleiotropic effects can be dissociated at a specific step insulin/IGF-1 pathway remains unknown. Through performing mutagenesis screen, we identified missense mutation daf-18(yh1) that alters cysteine to tyrosine DAF-18/PTEN phosphatase, which maintained long enhanced while improving reduced motility adult mutants. We showed decreased lipid phosphatase activity of DAF-18/PTEN, retaining partial protein activity. found DAF-16/FOXO restricted detrimental upregulation SKN-1/NRF2, contributing beneficial traits Our work provides important insights into how one evolutionarily conserved component, PTEN, coordinate animal health longevity.