Social and clinical frailty indices in aging mice: a comparative analysis of longitudinal and cross-sectional designs

Aging is a heterogeneous phenomenon provoked by biological processes that still need to be fully understood. Frailty is a relevant outcome of aging reflecting biological decline that can be quantified through indices measuring the accumulation of functional deficits. Age-related declines may occur across multiple domains of functioning, and longitudinal study designs may better characterize decline within aging individuals. Thus, it is imperative to characterize how frailty indices that capture different functional domains associate with one another over the natural lifespan and across study designs. Here, the clinical frailty index (CFI) and the mouse social frailty index (mSFI) were applied to male and female mice both longitudinally and cross-sectionally over the lifespan. An overall similar association with aging was apparent: within each cohort, both CFI and mSFI were strongly positively associated with age. The utility of the CFI and mSFI as age predictors within the longitudinal study was confirmed. Critically, a model developed within the longitudinal study based on CFI scores, mSFI scores, and sex was able to predict age better than alternative models using only one of the indices. This result suggests that the CFI and the mSFI capture intrinsically different elements of deficit accumulation with age. The same model also showed a good performance in predicting the age of mice in the cross-sectional study. Overall, these results demonstrate that the information captured by both frailty indices is relevant to aging, relationships between indices vary across study design, and both frailty domains are needed to produce better age predictions.