Submitted to: Journal of Gerontology Biological Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2016
Publication Date: 1/21/2017
Citation: Miller, M.G., Thangthaeng, N., Shukitt Hale, B. 2017. A clinically relevant frailty index for aging rats. Journal of Gerontology, Series A, Biological Sciences and Medical Sciences. doi:10.1093/gerona/glw338.
Interpretive Summary: Frailty is an important health concern for older adults. The present study develops a frailty index for use with a commonly used model of aging, the rat. Researchers from the USDA Agricultural Research Service evaluated a sample of 133 seventeen-month-old male rats on a series of motor tasks that measure strength, speed, physical activity, and endurance. Rats were ranked according to performance on each task, and rats that performed in the lowest 20% were identified as poor performers. Rats that performed poorly on 3-4 tasks were identified as frail while rats that performed poorly on 2 tasks were identified as mildly frail. Mildly frail rats were 3.8 times and frail rats were 27.5 times more likely to die during the 100 days following testing relative to non-frail rats. This frailty index is a useful screening and evaluation tool for preclinical frailty research.
Technical Abstract: Frailty is a clinical syndrome that is increasingly prevalent during aging. Frailty involves the confluence of reduced strength, speed, physical activity, and endurance, and it is associated with adverse health outcomes. Frailty indices have been developed to diagnose frailty in older adult populations, and a pre-clinical frailty index has been developed for the C57BL/6 mouse. The present study adapts these existing clinical and pre-clinical indices of frailty to the Fischer (F344) rat, which is commonly used in aging research. One hundred and thirty-three male F344 rats (17mo) completed a battery of commonly administered behavioral tasks, including: forelimb wire-hang (strength), rotarod (speed), open field (physical activity), and inclined screen (endurance). This age was selected because it provides adequate remaining lifespan in which to conduct an intervention study without undo mortality and at which age-related risk factors may still be modifiable. Within this cohort, rats whose performance put them in the lowest quintile were identified for each task, and the number of tasks on which a rat performed poorly determined their frailty index. Rats that performed poorly on two tasks were considered mildly frail (17.29%, n = 23), and rats that performed poorly on 3-4 tasks were considered frail (2.26%, n = 3). Logistic regression of 100-day survival revealed that mildly frail rats were 3.8 times and frail rats were 27.5 times more likely to die during that period than non-frail rats (p = 0.038; 95% CI: 2.030, 372.564). The selected criterion tests, cutoff points, and index provide a potential standardized definition for frailty in aged F344 rats that is consistent with existing frailty indices for humans and mice, and present a potentially useful tool for excluding frail animals which may not survive a chronic intervention study.