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

Park, Hae-Eun H.; Hwang, Wooseon; Ham, Seokjin; Kim, Eunah; Altintas, Ozlem; Park, Sangsoon; Son, Heehwa G.; Lee, Yujin; Lee, Dongyeop; Heo, Won Do; Lee, Seung-Jae V.

doi:10.1038/s41467-021-25920-w

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

Nature communications, v.12 no.1, 2021년, pp.5631 -

Park, Hae-Eun H. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Hwang, Wooseon (Department of Life Sciences, Pohang University of Science and Technology, Pohang, 37673 South Korea) , Ham, Seokjin (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Kim, Eunah (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Altintas, Ozlem (School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, 37673 South Korea) , Park, Sangsoon (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Son, Heehwa G. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Lee, Yujin (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141 South Korea) , Lee, Dongyeop (Department of Life Sciences, Pohang University of Science and Technolo) , Heo, Won Do , Lee, Seung-Jae V.

Abstract ▼ AI-Helper

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

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