The DOI matches its Crossref record; 294 of the 294 references it cites were found in a registry or an index.
Genetics of Human Longevity Within an Eco-Evolutionary Nature-Nurture Framework
Open accessAbstract
Human longevity is a complex trait, and to disentangle its basis has a great theoretical and practical consequences for biomedicine. The genetics of human longevity is still poorly understood despite several investigations that used different strategies and protocols. Here, we argue that such rather disappointing harvest is largely because of the extraordinary complexity of the longevity phenotype in humans. The capability to reach the extreme decades of human lifespan seems to be the result of an intriguing mixture of gene-environment interactions. Accordingly, the genetics of human longevity is here described as a highly context-dependent phenomenon, within a new integrated, ecological, and evolutionary perspective, and is presented as a dynamic process, both historically and individually. The available literature has been scrutinized within this perspective, paying particular attention to factors (sex, individual biography, family, population ancestry, social structure, economic status, and education, among others) that have been relatively neglected. The strength and limitations of the most powerful and used tools, such as genome-wide association study and whole-genome sequencing, have been discussed, focusing on prominently emerged genes and regions, such as apolipoprotein E, Forkhead box O3, interleukin 6, insulin-like growth factor-1, chromosome 9p21, 5q33.3, and somatic mutations among others. The major results of this approach suggest that (1) the genetics of longevity is highly population specific; (2) small-effect alleles, pleiotropy, and the complex allele timing likely play a major role; (3) genetic risk factors are age specific and need to be integrated in the light of the geroscience perspective; (4) a close relationship between genetics of longevity and genetics of age-related diseases (especially cardiovascular diseases) do exist. Finally, the urgent need of a global approach to the largely unexplored interactions between the 3 genetics of human body, that is, nuclear, mitochondrial, and microbiomes, is stressed. We surmise that the comprehensive approach here presented will help in increasing the above-mentioned harvest.
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
“Our findings could well be integrated within current ideas on the biology of aging which suggest that aging rates, and consequently lifespans, evolve as a function of trade-offs with other characters including social, cognitive, and reproductive capacities (Yang, et al. 2016; Giuliani, et al. 2018; Snyder-Mackler, et al. 2020).”
From DLX5/6 GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Giuliani, et al. 2018
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
Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Social Relationships and Mortality Risk: A Meta-analytic Review
Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000316 · Cited by 7,272
DNA methylation age of human tissues and cell types
Horvath, S. (2013) · Genome Biology · doi:10.1186/gb-2013-14-10-r115 · Cited by 7,075
Davey Smith, G., & Ebrahim, S. (2003) · International Journal of Epidemiology · doi:10.1093/ije/dyg070 · Cited by 5,882
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
Lloyd-Jones, D. M., Hong, Y., Labarthe, D., Mozaffarian, D., Appel, L. J., Van Horn, L., Greenlund, K., Daniels, S., Nichol, G., Tomaselli, G. F., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.192703 · Cited by 4,750
Pleiotropy, natural selection, and the evolution of senescence.
Williams, G. C. (1957) · Evolution · doi:10.1111/j.1558-5646.1957.tb02911.x · Cited by 4,279
Interactions Between the Microbiota and the Immune System
Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012) · Science · doi:10.1126/science.1223490 · Cited by 4,173
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891
Research works printed but not linked: 2
- 10.1016/j.mad.2017.01.008 · DOI
- Luca, B, Claudia, S, Nicola, M, Cristina, P, Cristina, G, Giovanni, M, Paolo, G, Oliviero, O, Giovanni, M, Claudio, F, Domenico, G. Clonal hematopoiesis of indeterminate potential (CHIP) in patients with coronary artery disease and in centenarians. Further clues linking chip with cardiovascular risk. 2017;130(suppl 1)1144.
Cited by
Sorted by citations
Melzer, D. R., Pilling, L. C., & Ferrucci, L. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0183-6 · Cited by 387
The Genetics of Aging: A Vertebrate Perspective
Singh, P. P., Demmitt, B. A., Nath, R. D., & Brunet, A. (2019) · Cell · doi:10.1016/j.cell.2019.02.038 · Cited by 259
“, Sardinia and Okinawa islands) could facilitate the identification of rare variants because of increased frequency in these populations (Giuliani et al., 2018) and decreased heterogeneity (Pala et al.”
BackgroundInfluentialThe Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity
Abondio, P., Sazzini, M., Garagnani, P., Boattini, A., Monti, D., Franceschi, C., Luiselli, D., & Giuliani, C. (2019) · Genes · doi:10.3390/genes10030222 · Cited by 240
Rampelli, S., Soverini, M., D’Amico, F., Barone, M., Tavella, T., Monti, D., Capri, M., Astolfi, A., Brigidi, P., Biagi, E., et al. (2020) · mSystems · doi:10.1128/msystems.00124-20 · Cited by 166
“Longevity has been described as the result of a complex combination of variables, deriving from genetics, lifestyle, and environment (1, 2).”
BackgroundMechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
Hwangbo, D., Lee, H., Abozaid, L. S., & Min, K. (2020) · Nutrients · doi:10.3390/nu12041194 · Cited by 173
Metadata
- Authors
- Giuliani, C., Garagnani, P., & Franceschi, C.
- Affiliations
- University of Oxford (GB)
- Karolinska Institutet (SE)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- Corresponding author
- Franceschi, Claudio
- Venue
- Circulation Research
- Published
- 2018-09-14
- Volume
- 123
- Issue
- 7
- Pages
- 745-772
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2890672865
- Cited by
- 92
- References
- 293
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 8 · 2023: 13 · 2022: 10 · 2021: 12 · 2020: 21 · 2019: 15 · 2018: 2
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
- Funders
- European Commission (602757, 634821)
- Ministry of Education and Science of the Russian Federation (074-02-2018-330)
- Lobachevsky State University of Nizhny Novgorod
- Horizon 2020 Framework Programme (634821)
- 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
- human longevity, gene-environment interaction, apolipoprotein E, FOXO3, interleukin-6, insulin-like growth factor I, chromosome 9p21, somatic mutations, pleiotropy, geroscience, age-related diseases, cardiovascular disease, mitochondrial genetics, microbiome, sex differences, socioeconomic status
- MeSH terms
- Healthy Aging, Age Factors, Animals, Cardiovascular Diseases, Humans, Longevity, Risk Factors, Risk Assessment, Evolution, Molecular, 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
