Epigenetic clocks and risk assessment in adult spinal deformity: A novel association between pace of aging with frailty, disability, and postoperative complications

Objective: Surgery for spinal deformity has the potential to improve pain, disability, function, self image, and mental health. These surgeries carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight on the molecular basis of frailty and improve current risk assessment tools. Methods: Adult patients undergoing deformity surgery were prospectively enrolled. Preoperative whole blood was used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC) based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both qPCR (T/S ratio) and methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiology (ASA) classification, and Charlson Comorbidity Index (CCI), Adult Spinal Deformity Frailty Index (ASDFI), Edmonton Frail Score (EFS), Oswestry Disability Index (ODI), and Scoliosis Research Society 22r (SRS22). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and log odd ratios derived from linear regression analyses, adjusted for gender and BMI, were performed. Results: Eighty-six patients were enrolled with mean age of 65 years and 46 women (54%). All patients underwent a posterior fusion with a mean of 11 levels fused and 35 3 column osteotomies (41%). Among epigenetic clocks, DunedinPACE showed a significant association with ASDFI, EFS, ASDFI, and SRS22, a higher pace of aging was associated with worse frailty and disability scores. PC PhenoAge showed significant associations with EFS, ASDFI, and ODI. PC GrimAge showed significant associations with EFS and ASD-FI. Among telomere measurements, PC DNAmTL was associated with CCI. There was a significant association between increased pace of aging by DunedinPACE and postoperative complications. Conclusions: DunedinPACE showed significant associations with markers of frailty (EFS, ASDFI), disability (ODI, SRS22), and postoperative complications. These data suggest a role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.