TY - JOUR
T1 - Centenarians as extreme phenotypes
T2 - An ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases
AU - Giuliani, Cristina
AU - Pirazzini, Chiara
AU - Delledonne, Massimo
AU - Xumerle, Luciano
AU - Descombes, Patrick
AU - Marquis, Julien
AU - Mengozzi, Giacomo
AU - Monti, Daniela
AU - Bellizzi, Dina
AU - Passarino, Giuseppe
AU - Luiselli, Donata
AU - Franceschi, Claudio
AU - Garagnani, Paolo
N1 - Il prof. C. Franceschi viene da altro Istituto e lavori con affiliazioni diverse usciranno ancora nei prossimi anni
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Age-related diseases
KW - Extreme phenotypes
KW - Gene–environment interactions
KW - Longevity
KW - Populations
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UR - http://www.scopus.com/inward/citedby.url?scp=85014413290&partnerID=8YFLogxK
U2 - 10.1016/j.mad.2017.02.007
DO - 10.1016/j.mad.2017.02.007
M3 - Review article
C2 - 28242236
AN - SCOPUS:85014413290
VL - 165
SP - 195
EP - 201
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
ER -