Background Emerging evidence suggests that there is significant variability in the progression of frailty in aging. We aimed to identify latent subpopulations of frailty trajectories, and examine their clinical and biological correlates. Methods We characterized frailty using a 41-item cumulative deficit score at baseline and annual visits up to 12 years in 681 older adults (55% women, mean age 74∙6 years). Clinical risk profile and walking while talking performance as a clinical marker of trajectories were examined. Mortality risk associated with trajectories was evaluated using Cox regression adjusted for established survival predictors, and reported as hazard ratios (HR). Proteome-wide analysis was done. Findings Latent class modeling identified 4 distinct frailty trajectories: relatively stable (34∙4%) as well as mild (36∙1%), moderate (24∙1%) and severely frail (5∙4%). Four distinct classes of frailty trajectories were also shown in an independent sample of 515 older adults (60% women, 68% White, 26% Black). The stable group took a median of 31 months to accumulate one additional deficit compared to 20 months in the severely frail group. The worst trajectories were associated with modifiable risk factors such as low education, living alone, obesity, and physical inactivity as well as slower walking while talking speed. In the pooled sample, mild (HR 2∙33, 95% CI 1∙30-4∙18), moderate (HR 2∙49, 95% CI 1∙33-4∙66), and severely frail trajectories (HR 5∙28, 95% CI 2∙68-10∙41) had higher mortality compared to the stable group. Proteomic analysis showed 11 proteins in lipid metabolism and growth factor pathways associated with frailty trajectories. Conclusion Frailty shows both stable and accelerated patterns in aging, which can be distinguished clinically and biologically.
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