Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring

Steve Horvath, Chiara Pirazzini, Maria Giulia Bacalini, Davide Gentilini, Anna Maria Di Blasio, Massimo Delledonne, Daniela Mari, Beatrice Arosio, Daniela Monti, Giuseppe Passarino, Francesco De Rango, Patrizia D'Aquila, Cristina Giuliani, Elena Marasco, Sebastiano Collino, Patrick Descombes, Paolo Garagnani, Claudio Franceschi

Research output: Contribution to journalArticlepeer-review


Given the dramatic increase in ageing populations, it is of great importance to understand the genetic and molecular determinants of healthy ageing and longevity. Semi-supercentenarians (subjects who reached an age of 105-109 years) arguably represent the gold standard of successful human ageing because they managed to avoid or postpone the onset of major age-related diseases. Relatively few studies have looked at epigenetic determinants of extreme longevity in humans. Here we test whether families with extreme longevity are epigenetically distinct from controls according to an epigenetic biomarker of ageing which is known as "epigenetic clock". We analyze the DNA methylation levels of peripheral blood mononuclear cells (PBMCs) from Italian families constituted of 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 semi-supercentenarians' offspring (mean age: 71.8 ± 7.8 years), and 47 age-matched controls (mean age: 69.8 ± 7.2 years). We demonstrate that the offspring of semi-supercentenarians have a lower epigenetic age than age-matched controls (age difference=5.1 years, p=0.00043) and that centenarians are younger (8.6 years) than expected based on their chronological age. By contrast, no significant difference could be observed for estimated blood cell counts (such as naïve or exhausted cytotoxic T cells or helper T cells). Future studies will be needed to replicate these findings in different populations and to extend them to other tissues. Overall, our results suggest that epigenetic processes might play a role in extreme longevity and healthy human ageing.

Original languageEnglish
Pages (from-to)1159-1170
Number of pages12
Issue number12
Publication statusPublished - 2015


  • Biomarker of ageing
  • DNA methylation
  • Epigenetic clock
  • Semi-supercentenarians
  • Semi-supercentenarians offspring

ASJC Scopus subject areas

  • Ageing
  • Cell Biology


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