Genetics of human longevity within an eco-evolutionary nature-nurture framework
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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.
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Our findings could 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.
“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 <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Giuliani, et al. 2018
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Longevity Areas and Mass Longevity
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Association of Genetic Polymorphisms with Longevity in the population of the Sardinian Blue ZonePreprint
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- 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
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