Identification of 12 genetic loci associated with human healthspan
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Abstract
Aging populations face diminishing quality of life due to increased disease and morbidity. These challenges call for longevity research to focus on understanding the pathways controlling healthspan. We use the data from the UK Biobank (UKB) cohort and observe that the risks of major chronic diseases increased exponentially and double every eight years, i.e., at a rate compatible with the Gompertz mortality law. Assuming that aging drives the acceleration in morbidity rates, we build a risk model to predict the age at the end of healthspan depending on age, gender, and genetic background. Using the sub-population of 300,447 British individuals as a discovery cohort, we identify 12 loci associated with healthspan at the whole-genome significance level. We find strong genetic correlations between healthspan and all-cause mortality, life-history, and lifestyle traits. We thereby conclude that the healthspan offers a promising new way to interrogate the genetics of human longevity.
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Genes that regulate lifespan in animal models and human studies, and multiple experimental paradigms, have demonstrated that it is possible to manipulate ageing biology to rejuvenate physiological functioning in complex model organisms.
“Genes that regulate lifespan in animal models6–9 and human studies10–14 as well as multiple experimental paradigms, such as caloric restriction, heterochronic parabiosis and partial epigenetic reprogramming, have demonstrated that it is possible to manipulate ageing biology to ‘rejuvenate’ physiological functioning in complex model organisms15–28.”
From Measuring biological age using omics data (2022) · cites this paper as [11]
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Ying, K., Zhai, R., Pyrkov, T. V., Mariotti, M., Fedichev, P. O., Shen, X., & Gladyshev, V. N. (2020) · medRxiv · doi:10.1101/2020.08.06.20169854 · Cited by 5 · see citing works
Self-citationIntegrative analyses uncover mechanisms by which aging drives B cell lymphomaPreprint
Castro, J. P., Shindyapina, A. V., Barbieri, A., Ying, K., Strelkova, O. S., Paulo, J. A., Tyshkovskiy, A., Meinl, R., Kerepesi, C., Petrashen, A. P., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.23.432500 · Cited by 4 · see citing works
Common DNA sequence variation influences epigenetic aging in African populations
Meeks, G. L., Scelza, B. A., Asnake, H. M., Prall, S. P., Patin, É., Froment, A., Fagny, M., Quintana‐Murci, L., Henn, B. M., & Gopalan, S. (2025) · Communications Biology · doi:10.1038/s42003-025-08893-0 · Cited by 17 · see citing works
- Authors
- Zenin, A., Tsepilov, Y., Sharapov, S., Getmantsev, E., Menshikov, L. I., Fedichev, P. O., & Aulchenko, Y.
- Affiliations
- Novosibirsk State University (RU)
- Moscow Institute of Physics and Technology (RU)
- Corresponding author
- Fedichev, Peter O.
- Venue
- Communications Biology
- Published
- 2019-01-30
- Volume
- 2
- Issue
- 1
- Pages
- 41-41
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC6353874
- OpenAlex
- W2952981231
- Cited by
- 170
- References
- 81
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 31 · 2023: 23 · 2022: 15 · 2021: 25 · 2020: 13 · 2019: 12 · 2018: 2
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Medical Research Council (MC_PC_17228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- healthspan, human longevity, genetic loci, aging, chronic disease risk, Gompertz mortality law, all-cause mortality, genetic correlation, life-history traits, genetic risk models
- MeSH terms
- Aged, Alleles, Female, United Kingdom, Health Status, Humans, Longevity, Male, Cluster Analysis, Computational Biology, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Genetic Association Studies, Molecular Sequence Annotation
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