We previously quantified frailty in aged mice with frailty index (FI) that used specialized equipment to measure health parameters. Here we developed a simplified, noninvasive method to quantify frailty through clinical assessment of C57BL/6J mice (5–28 months) and compared the relationship between FI scores and age in mice and humans. FIs calculated with the original performance-based eight-item FI increased from 0.06±0.01 at 5 months to 0.36±0.06 at 19 months and 0.38±0.04 at 28 months (n = 14). By contrast, the increase was graded with a 31-item clinical FI (0.02±0.005 at 5 months; 0.12±0.008 at 19 months; 0.33±0.02 at 28 months; n = 14). FI scores calculated from 70 self-report items from the first wave of the Survey of Health, Ageing and Retirement in Europe were plotted as function of age (n = 30,025 people). The exponential relationship between FI scores and age (normalized to 90% mortality) was similar in mice and humans for the clinical FI but not the eight-item FI. This noninvasive FI based on clinical measures can be used in longitudinal studies to quantify frailty in mice. Unlike the performance-based eight-item mouse FI, the clinical FI exhibits key features of the FI established for use in humans.

Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index. Here we show the results of extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 [1.04–1.05] in humans; 1.15 [1.12–1.18] in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.

We investigated the reliability of a newly developed clinical frailty index (FI) that measures frailty based on deficit accumulation in aging mice. FI scores were measured by two different raters independently in a large cohort (n = 233) of 343–430 day-old male C57BL/6J mice. Inter-rater reliability was evaluated with correlation coefficients, the kappa statistic, and intra-class correlation coefficients (ICC) in three separate groups of mice (n = 45, 50, and 138 mice/group) sequentially over 3 months. After each group was evaluated, descriptions of techniques used to identify health deficits were amended. Mice had comparable overall FI scores regardless of rater (0.213±0.002 vs 0.212±0.002; p = .802), although discordant measures declined as techniques were refined. Correlation coefficients (r 2 values) between raters improved throughout the study and mean kappa values increased (mean ± SEM; 0.621±0.018, 0.764±0.017, and 0.836±0.009 for groups 1, 2, and 3; p < .05). Values for intra-class correlation coefficient also improved from .51 (95% confidence interval = 0.11–.73) to .74 (0.54–0.85) and .77 (0.67–.83). FI scores increased over 3 months (p < .05), but did not differ between raters. These results show a high overall inter-rater reliability when the clinical FI tool is used to assess frailty in a large cohort of mice.

No abstract