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

Cristina Giuliani, Chiara Pirazzini, Massimo Delledonne, Luciano Xumerle, Patrick Descombes, Julien Marquis, Giacomo Mengozzi, Daniela Monti, Dina Bellizzi, Giuseppe Passarino, Donata Luiselli, Claudio Franceschi, Paolo Garagnani

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)195-201
Number of pages7
JournalMechanisms of Ageing and Development
Volume165
DOIs
Publication statusPublished - Jul 1 2017

Keywords

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

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology

Fingerprint Dive into the research topics of 'Centenarians as extreme phenotypes: An ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases'. Together they form a unique fingerprint.

Cite this