Centenarians as extreme phenotypes: an ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases
Abstract
In this review, we address the genetic continuum between aging and age-related diseases, with particular attention to the ecological perspective. We describe the connections between genes that promote longevity and genes associated with age-related diseases considering tradeoff mechanisms in which the same genetic variants could have different effects according to the tissue considered and could be involved in several biological pathways. Then we describe mechanisms of antagonistic pleiotropy, focusing on the complex interplay between genetic variants and environmental changes (internal or external). We sustain the use of centenarians as "super-controls" for the study of the major age-related diseases, starting from the concept that the maximization of the phenotypic differences in the considered cohort, achieved by selecting the most divergent phenotypes, could be useful for increasing the significant differences observed in the genetic association study. We describe the potential impact of the population genetic variability in the study of human longevity and the possible contribution of the past selective pressures in shaping the current genomic background of individuals. In conclusion, we illustrate recent findings emerged from whole-genome sequencing of long-lived individuals and future perspectives for interpreting the huge amount of genetic data that will be generated in the next future.
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Genes controlling more than one phenotypic trait can have been positively selected being favorable early in life and in adulthood but can become detrimental later in life.
“who proposes that genes controlling more than one phenotypic trait can have been positively selected being favorable early in life and in adulthood but can become detrimental later in life (old age and extreme longevity), phases of life subjected to weaker evolutionary pressures (Williams 1957; De Benedictis and Franceschi 2006; Giuliani, et al. 2017).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Giuliani, et al. 2017
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- Authors
- Giuliani, C., Pirazzini, C., Delledonne, M., Xumerle, L., Descombes, P., Marquis, J., Mengozzi, G., Monti, D., Bellizzi, D., Passarino, G., Luiselli, D., Franceschi, C., & Garagnani, P.
- Affiliations
- University of Bologna (IT)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- University of Verona (IT)
- University of Florence (IT)
- University of Calabria (IT)
- Corresponding author
- Giuliani, Cristina
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 165
- Issue
- Pt B
- Pages
- 195-201
- ISSN
- 0047-6374 (ISSN-L)
- OpenAlex
- W2594801926
- Cited by
- 43
- References
- 59
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 7
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- 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 › Evolution and Genetic Dynamics
- Keywords
- centenarians, human longevity, age-related diseases, antagonistic pleiotropy, genetic association studies, population genetic variation, natural selection
- MeSH terms
- Aged, 80 and over, Female, Humans, Longevity, Male, Phenotype, Genetic Variation, Genome-Wide Association Study, Gene-Environment Interaction
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