Epigenetic Age Versus Chronologic Age in Adult Spinal Deformity Surgery

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Determine whether epigenetic age (EA), calculated via DNA methylation analysis, is associated with early postoperative complications in adult spinal deformity (ASD) surgery. BACKGROUND: ASD is increasingly prevalent in the aging population, with postoperative complication rates ranging from 37% to 71%. While chronological age (CA) and frailty scores are known predictors of poor outcomes, they may not fully capture biological vulnerability. EA, derived from DNA methylation patterns, may better reflect a patient's physiological reserve and stress response capacity. METHODS: Thirty patients undergoing ASD surgery were prospectively enrolled and provided peripheral blood samples on the day of surgery. DNA methylation of peripheral blood mononuclear cells (PBMCs) was analyzed using the Illumina EPIC v2.0 array. EA was computed using the Horvath DNAmAge algorithm. Associations between EA, CA, and the Edmonton Frailty Index (EFI) with postoperative complications at 30 days were assessed using appropriate parametric and non-parametric statistical tests. Differentially methylated positions (DMPs) were identified between complication and non-complication group. RESULTS: Of the 30 enrolled patients (mean CA: 68.4 y, 21 female), 14 (47%) experienced postoperative complications. Sixty-three DMPs were found between the two groups, with 35 hypomethylated and 28 hypermethylated CpG sites in the complication group. Genes affected were linked to immune response, including LRBA and NFACT2. Regulators of EGFR and WNT pathways were also differentially methylated. Patients with EA greater than CA were significantly more likely to experience complications (86% vs. 14%, P=0.038). The difference between EA and CA was greater in the complication group (5.07 vs. 0.87 y, P=0.029). No significant differences were found in mean CA, EA, or EFI alone between the groups. CONCLUSION: Postoperative complications in ASD patients were associated with epigenetic alterations and elevated EA relative to CA. These findings suggest EA may be a novel biomarker for preoperative risk stratification in ASD surgery.