Aging-Related Multisystem Dysregulation Over the Adult Life Span and Physical Function in Later Life: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated. Methods: We tested the association of midlife Dm and its change over similar to 20 years with physical function in later life in 5 583 the Atherosclerosis Risk in Communities Study cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education. Results: Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the first quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the second-fourth quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between the annual growth rate of Dm and physical function. Conclusion: Greater Dm and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to the progression of Dm may highlight opportunities to preserve physical function.