title: Impact of Longevity Interventions on a Validated Mouse Clinical Frailty Index.
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.
authors.affiliation: Kolling 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.
authors.forename: Alice E
authors.initials: AE
authors.lastname: Kane
authors.affiliation: Kolling 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. sarah.hilmer@sydney.edu.au.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Hilmer
authors.affiliation: National Institute on Aging, Baltimore, Maryland.
authors.forename: Dawn
authors.initials: D
authors.lastname: Boyer
authors.affiliation: National Institute on Aging, Baltimore, Maryland.
authors.forename: Kristan
authors.initials: K
authors.lastname: Gavin
authors.affiliation: National Institute on Aging, Baltimore, Maryland.
authors.forename: Dawn
authors.initials: D
authors.lastname: Nines
authors.affiliation: Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Howlett
authors.affiliation: National Institute on Aging, Baltimore, Maryland.
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Mitchell
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D031204:Caloric Restriction; D005260:Female; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015203:Reproducibility of Results; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol
keywords: Aging; Calorie restriction; Frailty; Frailty index.; Mouse; Resveratrol