Trajectories of function and biomarkers with age: the CHS All Stars Study

Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways.

We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values.

Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories.

Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines.