Accelerated biological aging: unveiling the path to cardiometabolic multimorbidity, dementia, and mortality

Background: Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns. This prospective study used UK Biobank cohort to investigate the relationship between biological aging and the trajectory of CMM to dementia and mortality.

Methods: CMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms. Accelerated aging indicated biological age advances more rapidly than chronological age.

Results: The study included 415,147 individuals with an average age of 56.5 years. During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) in fully-adjusted Cox regression models (p < 0.05 for all). Accelerated aging had adjusted HRs of 1.489 (KDM-BA) and 1.488 (PhenoAge) for CMM, 1.434 (KDM-BA) and 1.514 (PhenoAge) for dementia, and 1.943 (KDM-BA) and 2.239 (PhenoAge) for mortality in participants with CMD at baseline (p < 0.05 for all). CMM significantly mediated accelerated aging's indirect effects on dementia by 13.7% (KDM-BA, HR) and 21.6% (PhenoAge); those on mortality were 4.7% (KDM-BA) and 5.2% (PhenoAge). The population attributable-risk of Life's Essential 8 score (≥80 vs. <80) were 0.79 and 0.43 for KDM-BA and PhenoAge accelerated aging, respectively.

Conclusion: Biological aging involves the entire trajectory of CMM from a CMD-free state to CMD, to CMM, and ultimately to dementia and death. Life's Essential 8 may be a potential target to counter age acceleration.