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Updated: Apr 17, 2026
Frailty Assessment in an Aging Mouse Model
Published on: September 23, 2025
Impact of Longevity Interventions on a Validated Mouse Clinical Frailty Index
Alice E Kane1, Sarah N Hilmer2, Dawn Boyer3
1Kolling Institute of Medical Research and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Abstract:
This article investigates the effect on the mouse frailty index (FI), of factors known to influence lifespan and healthspan in mice: strain (short-lived DBA/2J mice vs long-lived C57BL/6J mice), calorie restriction (CR), and resveratrol treatment. The mouse FI, based on deficit accumulation, was recently validated in C57BL/6J mice by Whitehead JC, Hildebrand BA, Sun M, et al. (A clinical frailty index in aging mice: comparisons with frailty index data in humans. J Gerontol A Biol Sci Med Sci. 2014;69:621-632) and shares many characteristics of the human FI. FI scores were measured in male and female aged (18 months) ad-libitum fed and CR DBA/2J and C57BL/6J mice, as well as male aged (24 months) C57BL/6J mice ad-libitum fed with or without resveratrol (100 mg/kg/day) in the diet for 6 months. Mean scores of two raters were used, and the raters had excellent inter-rater reliability (ICC = 0.88, 95% CI [0.80, 0.92]). Furthermore, the interventions of CR and resveratrol were associated with a significant reduction in FI scores in C57BL/6J mice, compared to age-matched controls. The short-lived DBA/2J mice also had slightly higher FI scores than the C57BL/6J mice, for the male calorie-restricted groups (DBA/2J FI = 0.16±0.03, C57BL/6J FI = 0.11±0.03, p = .01). This study uses the mouse FI developed by Whitehead JC, Hildebrand BA, Sun M, et al. (A clinical frailty index in aging mice: comparisons with frailty index data in humans. J Gerontol A Biol Sci Med Sci. 2014;69:621-632) in a different mouse colony and shows that this tool can be applied to quantify the effect of dietary and pharmaceutical interventions on frailty.
Insights
Calorie restriction and resveratrol treatment significantly reduced frailty index scores in aging mice, demonstrating their potential to improve healthspan. This study validates the mouse frailty index as a tool for assessing interventions.
Area of Science:
- Gerontology
- Aging research
- Biomedical sciences
Background:
- The mouse frailty index (FI) is a validated tool for quantifying aging and healthspan.
- Factors like mouse strain, calorie restriction (CR), and resveratrol influence lifespan and healthspan.
- Understanding these factors' impact on frailty is crucial for developing interventions.
Purpose of the Study:
- To investigate the effect of mouse strain, CR, and resveratrol on the mouse frailty index (FI).
- To assess the utility of the mouse FI in quantifying the impact of dietary and pharmaceutical interventions on frailty.
- To compare frailty levels between short-lived DBA/2J and long-lived C57BL/6J mouse strains.
Main Methods:
- Measured FI scores in aged male and female DBA/2J and C57BL/6J mice under ad-libitum feeding and CR conditions.
- Administered resveratrol (100 mg/kg/day) to aged C57BL/6J mice for 6 months.
- Utilized mean scores from two raters with excellent inter-rater reliability (ICC = 0.88).
Main Results:
- Calorie restriction and resveratrol treatment significantly reduced FI scores in C57BL/6J mice compared to controls.
- Short-lived DBA/2J mice exhibited slightly higher FI scores than C57BL/6J mice in male calorie-restricted groups (p = .01).
- The mouse FI effectively quantified the effects of CR and resveratrol interventions on frailty.
Conclusions:
- CR and resveratrol are effective interventions for reducing frailty in aging mice.
- The mouse FI is a reliable tool for assessing the efficacy of interventions targeting aging and healthspan.
- Findings support the translation of frailty assessment tools from humans to mice for aging research.
