Sex differences in epigenetic age in Mediterranean high longevity regions.
Level 4 - case-series / case-control
Cross-sectional observational biomarker study.
PubMed 36506464 · doi:10.3389/fragi.2022.1007098
What was done
DNA methylation predictors (Horvath, Hannum, GrimAge, PhenoAge, Skin and Blood, Pace of Aging, and surrogate markers for serum IL-6 and regulatory T cells) were analyzed to assess sex differences in biological aging among individuals living in two Mediterranean Blue Zones (Sardinia, Italy and Ikaria, Greece) characterized by equal male-to-female centenarian ratios.
What was found
Men displayed positive epigenetic age acceleration relative to women across all clocks, with significantly higher rates in GrimAge (beta = 3.55, p = 1.22e-12), Horvath (beta = 1.07, p = 0.00378), and Pace of Aging (beta = 0.0344, p = 1.77e-8). Men showed lower DNAm-predicted serum IL-6 (beta = -0.00301, p = 2.84e-12), while women showed higher DNAm-predicted regulatory T cell proportions (p = 0.0150, 95% CI [0.00131, 0.0117], Cohen's d = 0.517). Epigenetic clocks correlated better with chronological age in women than in men, but all clocks except PhenoAge (mean absolute error < 5 years) had large calibration errors (mean absolute error > 30 years) in both sexes.
Why it matters
Even in populations where male and female centenarian survival is balanced, men exhibit biologically accelerated epigenetic aging relative to women across most DNA methylation clocks.
Limits
The abstract does not state the sample size, participant age distribution, or inclusion criteria. The study relies on surrogate methylation-derived metrics rather than direct biological measurements of IL-6 or immune cell counts, and most clocks exhibited extreme mean absolute error (>30 years).
Cited by
- supports On average, females exhibit lower epigenetic age than chronological age-matched males.