{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin JR"],"funding":["NIA NIH HHS","NHGRI NIH HHS"],"pagination":["783-794"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12434795"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["1(9)"],"pubmed_abstract":["Extreme longevity in humans has a strong genetic component, but whether this involves genetic variation in the same longevity pathways as found in model organisms is unclear. Using whole-exome sequences of a large cohort of Ashkenazi Jewish centenarians to examine enrichment for rare coding variants, we found most longevity-associated rare coding variants converge upon conserved insulin/insulin-like growth factor 1 signaling and AMP-activating protein kinase signaling pathways. Centenarians have a number of pathogenic rare coding variants similar to control individuals, suggesting that rare variants detected in the conserved longevity pathways are protective against age-related pathology. Indeed, we detected a pro-longevity effect of rare coding variants in the Wnt signaling pathway on ind"],"journal":["Nature aging"],"pubmed_title":["Rare genetic coding variants associated with human longevity and protection against age-related diseases."],"pmcid":["PMC12434795"],"funding_grant_id":["P01 AG017242","U19 AG056278","R01 AG060747","R01 HG008153","R01 AG057909","R01 AG061155"],"pubmed_authors":["Vijg J","Sin-Chan P","Napolioni V","Niedernhofer LJ","Barzilai N","Gorg S","Franke A","Zhang ZD","Zhang Q","Laudes M","Mitra J","Suh Y","Wang Z","Jabalameli MR","Nebel A","Nguyen N","Shuldiner AR","Gorbunova V","Atzmon G","Regeneron Genetics Center","Robbins PD","Ladiges WC","Greicius MD","Milman S","Lin JR","Torres GG","Ye K","Gao T"],"additional_accession":[]},"is_claimable":false,"name":"Rare genetic coding variants associated with human longevity and protection against age-related diseases.","description":"Extreme longevity in humans has a strong genetic component, but whether this involves genetic variation in the same longevity pathways as found in model organisms is unclear. Using whole-exome sequences of a large cohort of Ashkenazi Jewish centenarians to examine enrichment for rare coding variants, we found most longevity-associated rare coding variants converge upon conserved insulin/insulin-like growth factor 1 signaling and AMP-activating protein kinase signaling pathways. Centenarians have a number of pathogenic rare coding variants similar to control individuals, suggesting that rare variants detected in the conserved longevity pathways are protective against age-related pathology. Indeed, we detected a pro-longevity effect of rare coding variants in the Wnt signaling pathway on ind","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-06-02T05:52:09.432Z","creation":"2026-04-14T03:14:07.011Z"},"accession":"S-EPMC12434795","cross_references":{"pubmed":["37117627"],"doi":["10.1038/s43587-021-00108-5"]}}