Guo · The journal of prevention of Alzheimer's disease 2026 · systematic review and meta-analysis · n=22 studies

Psychological adversities and epigenetic ageing in midlife and older age: A systematic review and meta-analysis.

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Level 3 - non-randomized controlled study

Systematic review and meta-analysis of observational studies

PubMed 42566822 · doi:10.1016/j.tjpad.2026.100650 · record verified 2026-08-31

What was done

The authors conducted a systematic review and random-effects meta-analysis across five databases up to July 2025 assessing the relationship between psychological adversities and epigenetic age acceleration (EAA) in midlife and older adults. Study quality was evaluated using an adapted Newcastle-Ottawa scale.

What was found

Twenty-two studies were included, with fifteen classified as high quality. Positive associations were consistently reported for second-generation clocks (PhenoAge and GrimAge). Meta-analyses showed that EAA was significantly associated with loneliness (β = 0.07, 95% CI [0.06, 0.08], I² = 0%, p = 0.002), depression (β = 0.08, 95% CI [0.04, 0.13], I² = 55.2%, p = 0.003), and stress (β = 0.10, 95% CI [0.03, 0.16], I² = 68.4%, p = 0.009).

Why it matters

This review links multiple forms of psychological adversity in midlife and older age to accelerated biological aging, highlighting the utility of second-generation epigenetic clocks in stress-aging research.

Limits

The total number of individual participants was not reported in the abstract. Substantial statistical heterogeneity was observed for depression and stress. Non-Western populations were underrepresented, anxiety was not studied, and the observational design cannot establish whether reducing psychological adversity decelerates biological aging.

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