The genetics of human longevity

Miriam Capri, Stefano Salvioli, Federica Sevini, Silvana Valensin, Laura Celani, Daniela Monti, Graham Pawelec, Giovanna De Benedictis, Efstathios S. Gonos, Claudio Franceschi

Research output: Contribution to journalArticlepeer-review

Abstract

Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify "longevity genes" in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of "candidate" polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes-positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF-α, TGF-β, TLR-4, PPARγ), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66shc) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.

Original languageEnglish
Pages (from-to)252-263
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1067
Issue number1
DOIs
Publication statusPublished - May 2006

Keywords

  • Apolipoproteins
  • CETP
  • IL-1 cluster
  • IL-10
  • IL-6
  • insulin/IGF-1
  • Longevity genes
  • p53, p66
  • PON1
  • PPARγ
  • TGF-β
  • TLR-4
  • TNF-α

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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