PHYSICAL PERFORMANCE IN AGED RATS PREDICTS LONGEVITY: IMPLICATIONS FOR ASSESSING PRECLINICAL INTERVENTIONS
C.S. Carter*, G. Onder, W.E. Sonntag, M. Pahor
Wake Forest University School of Medicine, Department of Internal Medicine: Section on Gerontology and Geriatrics and Department of Physiology and Pharmacology
Physical performance declines with age and low scores on standardized physical performance measures independently predict the incidence of disability, institutionalization and longevity in non-disabled older persons. There are limited data on the age-related decline in physical performance in healthy aging animals and how this might predict longevity. We prospectively assessed the changes in standardized physical performance measures in a cohort of 24 month-old healthy aging Brown Norway X Fisher 344 rats from the NIA colony. A total of 48 male rats, mean weight 573 + 16 g, fed ad libitum, were followed for 6 months. Swimming speed, spontaneous locomotor activity in a computerized photocell chamber, and time to drop from a 60 degree inclined plane were measured monthly. Over 3 months, performance deteriorated progressively and significantly in the swimming speed and inclined plane tests (both ps <.001). Performance in several domains of spontaneous locomotor activity, including horizontal and vertical motion and speed, did not change significantly over time. These data show that physical performance measured under high stress conditions declines progressively as a function of age in healthy rats. Most importantly, individual and summary physical performance scores measured at baseline, predicted longevity over nine months of follow-up (p = .003). This finding shows that physical performance measures in healthy older rats have similar predictive validity for longevity as that shown in human studies. While the immediate causes of death are substantially different in rats from those in humans, physical performance had similar predictive validity in both species, suggesting that the interspecies physical performance/survival association is independent of the immediate causes of death and may be influenced by biological and genetic mechanisms as well. An important aspect of this research is that we have defined and provided face validity of an assessment process of physical function that can be applied to several models of aging in small animals. This assessment model can be employed to study biological mechanisms that contribute to the age-related decline in physical function and possibly to the disabling process. For example, these assessments can be evaluated in rats deficient in growth hormone, an anabolic hormone known to play a vital role in maintaining tissue viability in old age, or rats treated with cytokines, that have been shown to induce muscle loss. These standardized assessments in small animals may also be used for preclinical testing of novel interventions for preventing the age-related declines in physical function. This approach is innovative, as such interventions are currently directly tested in humans, with no preclinical testing in an animal model of the condition these interventions are intended to cure or prevent. This research begins to address this important gap.
Key words:
physical disability, aging, sarcopenia, longevity, animal models
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