Rare genetic coding variants associated with human longevity and protection against age-related diseases.
Journal
Nature aging
ISSN: 2662-8465
Titre abrégé: Nat Aging
Pays: United States
ID NLM: 101773306
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
08
12
2020
accepted:
05
08
2021
medline:
1
9
2021
pubmed:
1
9
2021
entrez:
28
4
2023
Statut:
ppublish
Résumé
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 individuals harboring the known common risk allele APOE4. The genetic component of extreme human longevity constitutes, at least in part, rare coding variants in pathways that protect against aging, including those that control longevity in model organisms.
Identifiants
pubmed: 37117627
doi: 10.1038/s43587-021-00108-5
pii: 10.1038/s43587-021-00108-5
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
783-794Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG008153
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061155
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG060747
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057909
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG017242
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG056278
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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