Cited by 380Genetics, Aging, and Longevity in Model OrganismsGenetic Associations and EpidemiologyGenetics and Physical Performance

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Genetics of healthy aging and longevity

Open access

Brooks-Wilson, Angela R.·2013·Human Genetics

DOI 10.1007/s00439-013-1342-zPMC PMC3898394

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Abstract

Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may 'buffer' the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.

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Additional file 3 of Association between gut microbiota and longevity: a genetic correlation and mendelian randomization study
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Additional file 4 of Interrelationships and determinants of aging biomarkers in cord blood
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Additional file 2 of Interrelationships and determinants of aging biomarkers in cord blood
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Additional file 4 of Association between gut microbiota and longevity: a genetic correlation and mendelian randomization study
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Mercier, J., Guérin, O., Michel, É., Chorin, F., Loubat, A., Gautier, N., Rousseau, A., & Colson, S. S. (2026) · GeroScience · doi:10.1007/s11357-026-02504-4
Why Some People Live Past 100: The Role of the Immune System in Centenarians, Semi-Supercentenarians and Supercentenarians
Caruso, C., Accardi, G., Aiello, A., Calabrò, A., Puleo, C., Zarcone, R., & Candore, G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188420

Authors: Brooks-Wilson, A. R.
Affiliations: BC Cancer Agency (CA)
Corresponding author: Brooks-Wilson, Angela R.
ORCID: Brooks-Wilson, Angela R.
Venue: Human Genetics
Publisher: Springer Science and Business Media LLC
Published: 2013-08-08
Volume: 132
Issue: 12
Pages: 1323-1338
ISSN: 0018-7348 (ISSN-L)
0340-6717
1432-1203
DOI: 10.1007/s00439-013-1342-z
PMC: PMC3898394
OpenAlex: W2072130124
Cited by: 380
References: 123
Citations by year: 2026: 17 · 2025: 31 · 2024: 40 · 2023: 33 · 2022: 34 · 2021: 43 · 2020: 25 · 2019: 26 · 2018: 30 · 2017: 24 · 2016: 23 · 2015: 35 · 2014: 19
FWCI: 1.58
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/2.0 (unspecified)
Locations: Human Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords: healthy aging, longevity, centenarians, apolipoprotein E, FOXO3, chromosome 3, genome-wide association study, candidate genes, gene-environment interaction, rare alleles, epigenetics, DNA methylation, lifestyle factors, age-related diseases, population stratification
MeSH terms: Aging, Health, Humans, Life Expectancy, Genetic Linkage, Longevity, Genetic Variation, Epigenesis, Genetic, Genome-Wide Association Study, Gene-Environment Interaction

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