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Mech Ageing Dev. 2017 Jul;165(Pt B):195-201. doi: 10.1016/j.mad.2017.02.007. Epub 2017 Feb 27.

Centenarians as extreme phenotypes: An ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases.

Author information

1
Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy. Electronic address: cristina.giuliani2@unibo.it.
2
Institute of Neurological Sciences of Bologna (IRCCS), Bologna, Italy.
3
Department of Biotechnologies, University of Verona, Verona, Italy.
4
Functional Genomics, Nestle Institute of Health Sciences, 1015 Lausanne, Switzerland.
5
Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy.
6
Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy.
7
Department of Ecology, Biology, and Earth Sciences, University of Calabria, Rende (CS), Italy.
8
Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy.

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.

KEYWORDS:

Age-related diseases; Extreme phenotypes; Gene–environment interactions; Longevity; Populations

PMID:
28242236
DOI:
10.1016/j.mad.2017.02.007
[Indexed for MEDLINE]

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