“Centenarians Consistently Present a Younger Epigenetic Age Than Their Chronological Age With 4 Epigenetic Clocks Based on a Small Number of CpG Sites”, Antoine Daunay, Lise M. Hardy, Yosra Bouyacoub, Mourad Sahbatou, Mathilde Touvier, Hélène Blanché, Jean-François Deleuze, Alexandre How-Kit2022-10-03 ()⁠:

Aging is a progressive time-dependent biological process affecting differentially individuals, who can sometimes present exceptional longevity. Epigenetic alterations are one of the hallmarks of aging, which comprise the epigenetic drift and clock at DNA methylation level.

In the present study, we estimated the DNA methylation-based age (DNAmage) using 4 epigenetic clocks based on a small number of CpGs in French centenarians and semi-supercentenarians (CSSC, n = 214) as well as nonagenarians’ [90–99yo] and centenarians’ offspring (NCO, n = 143) compared to individuals from the French general population (CG, n = 149).

DNA methylation analysis of the 9 CpGs included in the epigenetic clocks showed high correlation with chronological age (−0.66>R>0.54) and also the presence of an epigenetic drift for 4 CpGs that was only visible in CSSC. DNAmage analysis showed that CSSC and to a lesser extend NCO present a younger DNAmage than their chronological age (15–28.5 years for CSSC, 4.4–11.5 years for NCO and 4.2–8.2 years for CG), which were strongly statistically-significant in CSSC compared to CG (p-values<2.2 × 10−16).

These differences suggest that epigenetic aging and potentially biological aging are slowed in exceptionally long-lived individuals and that epigenetic clocks based on a small number of CpGs are sufficient to reveal alterations of the global epigenetic clock.