The DOI matches its Crossref record; 123 of the 123 references it cites were found in a registry or an index.
Genetics of healthy aging and longevity
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the ɛ4 allele is a strong genetic risk factor for Alzheimer disease,20 and by far the strongest hit in genome-wide association studies of longevity.21,22”
From Plasma levels of apolipoprotein E, APOE genotype, and all-cause and cause-specific mortality in 105 949 individuals from a white general population cohort (2019) · cites this paper as [22]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Principal components analysis corrects for stratification in genome-wide association studies
Price, A. L., Patterson, N. J., Plenge, R. M., Weinblatt, M. E., Shadick, N. A., & Reich, D. (2006) · Nature Genetics · doi:10.1038/ng1847 · Cited by 10,248
Genome-wide methylation profiles reveal quantitative views of human aging rates
Hannum, G., Guinney, J., Zhao, L., Zhang, L., Hughes, G., Sadda, S., Klotzle, B., Bibikova, M., Fan, J.-B., Gao, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.016 · Cited by 4,270
Aging, natural death, and the compression of morbidity
Fries, J. F. (1980) · New England Journal of Medicine · doi:10.1056/nejm198007173030304 · Cited by 3,356
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · cited 2×
“The use of principal components analysis (Price et al. 2006) or genomic controls (Devlin and Roeder 1999) can mitigate this problem, as can the conduct of studies within specific ethnic groups (Barzilai et al. 2001).”
BackgroundHsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270
Signals from the reproductive system regulate the lifespan of C. elegans
Hsin, H., & Kenyon, C. J. (1999) · Nature · doi:10.1038/20694 · Cited by 1,014
Herskind, A. M., McGue, M., Holm, N. V., Sørensen, T. I. A., Harvald, B., & Vaupel, J. W. (1996) · Human Genetics · doi:10.1007/bf02185763 · Cited by 879
Distinct DNA methylomes of newborns and centenarians
Heyn, H., Li, N., Ferreira, H. J., Moran, S., Pisano, D. G., Gomez, A., Diez, J., Sanchez-Mut, J. V., Setien, F., Carmona, F. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120658109 · Cited by 802
Intra-individual Change Over Time in DNA Methylation With Familial Clustering
Bjornsson, H. T. (2008) · JAMA · doi:10.1001/jama.299.24.2877 · Cited by 702
Bell, J. T., Tsai, P.-C., Yang, T.-P., Pidsley, R., Nisbet, J. P., Glass, D., Mangino, M., Zhai, G., Zhang, F., Valdes, A. M., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002629 · Cited by 700
Research works printed but not linked: 1
- Deelen J, Uh HW, Monajemi R, van Heemst D, Thijssen PE, Bohringer S, van den Akker EB, de Craen AJ, Rivadeneira F, Uitterlinden AG, Westendorp RG, Goeman JJ, Slagboom PE, Houwing-Duistermaat JJ, Beekman M (2013) Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin/IGF-1 signaling and telomere maintenance pathways. Age (Dordr) 35:235–249 · DOI
Cited by
Sorted by citations
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines
Rea, I. M., Gibson, D. S., McGilligan, V., McNerlan, S. E., Alexander, H. D., & Ross, O. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00586 · Cited by 1,267
White, M. C., Holman, D. M., Boehm, J. E., Peipins, L. A., Grossman, M., & Jane Henley, S. (2014) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2013.10.029 · Cited by 762
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723
Long live FOXO : unraveling the role of FOXO proteins in aging and longevity
Martins, R., Lithgow, G. J., & Link, W. (2015) · Aging Cell · doi:10.1111/acel.12427 · Cited by 758
Towards a comprehensive public health response to population ageing
Beard, J., & Bloom, D. E. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61461-6 · Cited by 612
Metadata
- Authors
- Brooks-Wilson, A. R.
- Affiliations
- BC Cancer Agency (CA)
- Corresponding author
- Brooks-Wilson, Angela R.
- Venue
- Human Genetics
- Published
- 2013-08-08
- Volume
- 132
- Issue
- 12
- Pages
- 1323-1338
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
