Role of epigenetics in human aging and longevity: Genome-wide DNA methylation profile in centenarians and centenarians' offspring

Davide Gentilini, Daniela Mari, Davide Castaldi, Daniel Remondini, Giulia Ogliari, Rita Ostan, Laura Bucci, Silvia M. Sirchia, Silvia Tabano, Francesco Cavagnini, Daniela Monti, Claudio Franceschi, Anna Maria Di Blasio, Giovanni Vitale

Research output: Contribution to journalArticle

Abstract

The role of epigenetics in the modulation of longevity has not been studied in humans. To this aim, (1) we evaluated the DNA methylation from peripheral leukocytes of 21 female centenarians, their 21 female offspring, 21 offspring of both non-long-lived parents, and 21 young women through ELISA assay, pyrosequencing analysis of Alu sequences, and quantification of methylation in CpG repeats outside CpG islands; (2) we compared the DNA methylation profiles of these populations through Infinium array for genome-wide CpG methylation analysis. We observed an age-related decrease in global DNA methylation and a delay of this process in centenarians' offspring. Interestingly, literature data suggest a link between the loss of DNA methylation observed during aging and the development of age-associated diseases. Genomewide methylation analysis evidenced DNA methylation profiles specific for aging and longevity: (1) aging-associated DNA hypermethylation occurs predominantly in genes involved in the development of anatomical structures, organs, and multicellular organisms and in the regulation of transcription; (2) genes involved in nucleotide biosynthesis, metabolism, and control of signal transmission are differently methylated between centenarians' offspring and offspring of both non-long-lived parents, hypothesizing a role for these genes in human longevity. Our results suggest that a better preservation of DNA methylation status, a slower cell growing/metabolism, and a better control in signal transmission through epigenetic mechanisms may be involved in the process of human longevity. These data fit well with the observations related to the beneficial effects of mild hypothyroidism and insulinlike growth factor I system impairment on the modulation of human lifespan.

Original languageEnglish
Pages (from-to)1961-1973
Number of pages13
JournalAge
Volume35
Issue number5
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Aging
  • Centenarians' offspring
  • DNA methylation
  • Epigenetics
  • Longevity. Centenarians

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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