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• Research Paper Volume 7, Issue 12 pp 1159-1170

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

  Relevance score: 17.557928

  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

  Keywords: semi-supercentenarians, semi-supercentenarians offspring, DNA methylation, epigenetic clock, biomarker of ageing

  Published in Aging on December 15, 2015

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  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

  

  (A) Scatter plot relating the DNAm age of each PBMC sample (y-axis) versus chronological age (x-axis). Points are colored by status. The color of each dot corresponds to the status of each PBMC sample: red for centenarians, orange for offspring of centenarians, grey for controls. The black line corresponds to y=x. The orange line depicts the regression line based on the offspring of centenarians and centenarians (orange and red dots). The vertical distance to the orange line corresponds to the universal measure of age acceleration Age Accel. The bar plots depict group status (x-axis) versus (B, C) universal age acceleration, (D, E) intrinsic age acceleration, (F) extrinsic age acceleration. Each bar plot depicts the mean value, one standard error, and reports the p-value results from a non-parametric group comparison test (Kruskal Wallis test).

  
  
  

  

  Group status (offspring of semi-supercentenarian or control) versus estimated abundance of (A) exhausted cytotoxic T cells, (B) naïve cytotoxic T cells, (C) naïve helper T cells, (D) cytotoxic T cells, (E) helper T cells, (F) natural killer cells, (G) B cells, (H) monocytes. Each bar plot reports the mean value and one standard error. The p-value results from a non-parametric group comparison test (Kruskal Wallis). The abundance measures of blood cell counts were estimated based on DNA methylation levels using the epigenetic clock software. Roughly speaking, the y-axis of (A) reports a percentage while that for (B, C) corresponds to counts but it is best to interpret the y-axis in (A-C) as ordinal abundance measure. The y-axis in (D-H) reports estimated proportions based on the Houseman method [78].

  
  
  

  

  Group status (semi-supercentenarian, offspring of semi-supercentenarian, or control) versus estimated abundance of (A) exhausted cytotoxic T cells, (B) naïve cytotoxic T cells, (C) naïve helper T cells, (D) cytotoxic T cells, (E) helper T cells, (F) natural killer cells, (G) B cells, (H) monocytes. Each bar plot reports the mean value and one standard error. The p-value results from a non-parametric group comparison test (Kruskal Wallis). Roughly speaking, the y-axis of (A) reports a percentage while that for (B, C) corresponds to counts but it is best to interpret the y-axis in (A-C) as ordinal abundance measure. The y-axis in (D-H) reports estimated proportions based on the Houseman method [78].