Horvath · Aging 2015 · cross-sectional case-control study · n=192

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

Cited 338 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional case-control study comparing epigenetic age across family groups

PubMed 26678252 · doi:10.18632/aging.100861 · record verified 2026-08-30

What was done

The authors analyzed DNA methylation levels using the epigenetic clock in peripheral blood mononuclear cells (PBMCs) from Italian families. The study evaluated 82 semi-supercentenarians (mean age: 105.6 ± 1.6 years), 63 offspring of semi-supercentenarians (mean age: 71.8 ± 7.8 years), and 47 age-matched controls without long-lived parents (mean age: 69.8 ± 7.2 years). Estimated blood cell subtype counts were also compared across groups.

What was found

Offspring of semi-supercentenarians had a significantly lower epigenetic age than age-matched controls (age difference = 5.1 years, p = 0.00043). Semi-supercentenarians were epigenetically 8.6 years younger than expected based on chronological age. Estimated blood cell counts (including naïve or exhausted cytotoxic T cells and helper T cells) showed no significant differences between groups.

Why it matters

This paper provides evidence that extreme longevity and healthy aging are associated with preserved epigenetic profile youthfulness that is transmissible or shared between semi-supercentenarians and their offspring.

Limits

The study is observational and cross-sectional, precluding causal inference. It is limited to PBMCs in a single Italian cohort of modest sample size (total n = 192), and it did not examine other tissues or account for unmeasured lifestyle and environmental factors.

Cited by