Epigenetic Biological Age as a Preoperative Risk Biomarker for Surgical Recovery: A Narrative Review

Chronological age is a widely used but imprecise predictor of postoperative recovery and wound healing. Biological age, quantified via DNA methylation–based epigenetic clocks, has emerged as a more accurate proxy of physiological resilience. In the perioperative context, epigenetic regulation, including DNA methylation, histone modifications, and chromatin remodeling, has been shown to influence immune response, inflammation, and recovery trajectories following surgical stress. In aging biology, epigenetic clocks correlate strongly with mortality, frailty, and functional decline, while age-related epigenetic changes impair tissue repair and promote fibrosis. Experimental and clinical studies describe the regulatory landscape of acute and chronic wound healing, including roles for DNA methylation, chromatin remodeling, and miRNA signaling. Longitudinal perioperative studies further demonstrate acute and persistent methylation shifts following major surgery, notably within immune-inflammatory gene networks. This narrative review synthesizes foundational and contemporary literature on epigenetic regulation and biological aging in the context of wound repair, integrating mechanistic and translational perspectives. We examine how accelerated biological aging may forecast impaired wound recovery, highlighting molecular pathways as crucial translational targets. We further propose a structured clinical validation framework and identify critical research gaps, including the urgent need for prospective surgical cohorts and the underrepresentation of Pacific Islander and other non-European-ancestry populations in epigenetic clock development. If validated, epigenetic biomarkers could transform preoperative evaluation, enable individualized prehabilitation, and advance precision surgical medicine.