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No Evidence That Genetic Variation at the Klotho Locus Is Associated With Longevity in Caucasians from the Newcastle 85+ Study and the UK Biobank

Lookup NU author(s): Professor Heather Cordell, Dr Carmen Martin-RuizORCiD, Dr Louise Robinson, Emeritus Professor Thomas Kirkwood, Fotios Drenos



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. The demographics of Western populations are changing, with an increase in the proportion of older adults. There is evidence to suggest that genetic factors may influence the aging process: studying these may lead to interventions to help individuals live a longer and healthier life. Evidence from several groups indicates that Klotho (KL), a gene encoding a single-pass transmembrane protein that acts as an FGF23 co-receptor, may be associated with longevity and healthy aging. We aimed to explore this area further by comparing the genotype counts in 642 long-lived individuals from the Newcastle 85+ Study with 18 295 middle-aged Newcastle-based controls from the UK Biobank to test whether variants at the KL gene locus are over- or under-represented in older individuals. If KL is associated with longevity, then we would expect the genotype counts to differ between the 2 cohorts. We found that the rs2283368 CC genotype and the rs9536338 C allele, but not the KL-VS haplotype, were associated with reaching very old age. However, these associations did not replicate in the remainder of the UK Biobank cohort. Thus, our results do not reliably support the role of KL as a longevity factor.

Publication metadata

Author(s): Amin HA, Cordell HJ, Martin-Ruiz C, Robinson L, Kirkwood T, Blakemore AI, Drenos F

Publication type: Article

Publication status: Published

Journal: The Journals of Gerontology Series A

Year: 2022

Volume: 77

Issue: 3

Pages: 457-461

Online publication date: 05/12/2021

Acceptance date: 28/10/2021

Date deposited: 06/04/2022

ISSN (print): 1079-5006

ISSN (electronic): 1758-535X

Publisher: Oxford University Press


DOI: 10.1093/gerona/glab361

PubMed id: 34893828


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Funder referenceFunder name
CH-2008-1200Unilever UK Central Resources Limited
CM/GW 25/9/06
G0601333Medical Research Council (MRC)
MR/J50001X/1Medical Research Council (MRC)
NIHR Senior Investigator Award
PG/08/026/24712British Heart Foundation
R124/0509Dunhill Medical Trust