Abstract
This study examined the associations of biological age accelerations (BAAs) – KDM-BA acceleration (via Klemera and Doubal’s method) and PhenoAge acceleration (epigenetics-based), defined as residuals from regressing each biological age estimate on chronological age (CA) – with multimorbidity progression (measured by the Charlson Comorbidity Index, CCI), compared to CA. Utilizing UK Biobank data (n = 317,835; median follow-up: 13 years), Cox regression models adjusted for sex, ethnicity, lifestyle, and socioeconomic factors showed that each 1-year increase in KDM-BA acceleration raised the risk of CCI progression by 9.9% (HR [95% CI]: 1.099 [1.094-1.104]) and in PhenoAge acceleration by 4.3% (HR [95% CI]: 1.043 [1.041-1.044]). Consistent results were found in subgroup, sensitivity, and restricted cubic spline analyses, with PhenoAge acceleration achieving the highest predictive performance (C-index = 0.6755) compared to KDM-BA acceleration (0.6734) and CA (0.6701). These findings support the use of BAAs as cost-effective tools for assessing the risk of multimorbidity progression.