Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: The lesson of centenarians

Claudio Franceschi, Fabiola Olivieri, Francesca Marchegiani, Maurizio Cardelli, Luca Cavallone, Miriam Capri, Stefano Salvioli, Silvana Valensin, Giovanna De Benedictis, Angelo Di Iorio, Calogero Caruso, Giuseppe Paolisso, Daniela Monti

Research output: Contribution to journalArticlepeer-review

Abstract

In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest that a common core of master genes and metabolic pathways are responsible for aging and longevity across animal species. Moreover, in the concern of our plan to discover new genetic factors related to longevity, we explored the possibility to by-pass the need of an a-priori choice of candidate genes, extending the search to genes and genomic regions of still unknown function. Alu sequences may be considered as good markers of highly variable and potentially unstable loci in functionally important genomic regions. We extensively screened Alu-rich genomic sites and found a new genomic region associated with longevity.

Original languageEnglish
Pages (from-to)351-361
Number of pages11
JournalMechanisms of Ageing and Development
Volume126
Issue number2
DOIs
Publication statusPublished - Feb 2005

Keywords

  • Centenarians
  • Genetic polymorphism
  • Immunogenetics
  • Longevity

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

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