title: 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.
authors.affiliation: 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.
authors.forename: Cristina
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Institute of Neurological Sciences of Bologna (IRCCS), Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pirazzini
authors.affiliation: Department of Biotechnologies, University of Verona, Verona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Delledonne
authors.affiliation: Department of Biotechnologies, University of Verona, Verona, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Xumerle
authors.affiliation: Functional Genomics, Nestle Institute of Health Sciences, 1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: Functional Genomics, Nestle Institute of Health Sciences, 1015 Lausanne, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Marquis
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Mengozzi
authors.affiliation: Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.affiliation: Department of Ecology, Biology, and Earth Sciences, University of Calabria, Rende (CS), Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Bellizzi
authors.affiliation: Department of Ecology, Biology, and Earth Sciences, University of Calabria, Rende (CS), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.affiliation: Department of Biological, Geological, and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.affiliation: Institute of Neurological Sciences of Bologna (IRCCS), Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.affiliation: Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy; Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
mesh_terms: D000369:Aged, 80 and over; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D010641:Phenotype
keywords: Age-related diseases; Extreme phenotypes; Gene–environment interactions; Longevity; Populations