Accelerated aging in psychiatric disorders: evidence from epigenetic clocks

Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are among the most prevalent severe mental illnesses worldwide. These disorders are associated with substantial disability and premature mortality, primarily attributed to chronic somatic comorbidities and adverse effects of pharmacological treatments. Excess mortality and multiple medical age-related comorbidities are indicators of accelerated biological aging. The epigenetic clock, a biomarker of biological aging, and its derivative measure, epigenetic age acceleration (EAA), hold promise as emerging tools for investigating disorder-specific aging patterns and exploring underlying mechanisms and are being actively explored in this context. However, inconsistencies in findings arise from methodological heterogeneity across studies, and the biological validity of existing epigenetic clocks remains to be fully established. This review synthesizes recent advances in epigenetic aging research about these psychiatric disorders. It further examines associated molecular mechanisms, considers their relevance for clinical prediction, and explores implications for therapeutic interventions, thereby aiming to advance the mechanistic understanding within precision psychiatry.