Abstract LB-107: Aptitude for running in mice is age and strain-dependent but not predictive of tumor response

Abstract

Abstract Quality of life is a major consideration in attempting to design intervention strategies for delaying aging and age-related diseases. Preclinical studies depend on the use of reliable animal models, and the mouse has been used extensively in this regard. Quality of life can be evaluated in mice by measuring the functional status of various organ and physiological systems that are important in the health/physiological performance of an animal and that are shown to change with age in mice and/or humans. These physiological parameters would then be predicted to give a read-out of the animal's functional status relevant to human aging and quality of life. We conducted various assays of physiological function over the lifespan of male C57Bl/6 and BC6 F1 mice at 4, 12, 20, and 28 months of age. We report here on the correlation of running activity with tumor response. The inclination and capacity of mice to engage in voluntary spontaneous activity is a viable measure of their general physical aptitude. Response to the B16 melanoma tumor cell line is a measure of the host microenvironment to enhance or suppress tumor progression. We used in-cage running wheels connected to computers with monitoring software to assess the speed, distance and time the mice engaged in running behavior. Two months later, 1x105 B16 melanoma tumor cells were injected subcutaneously into the left inguinal space and repeated in the right axillary space. At 14 days post-injection, mice were terminated and tumors weighed and measured for size. Cohort numbers were 11-12 mice per age group and genotype. Four-month-old CB6 F1 mice ran further and had less tumor volume than age-matched B6 mice (16 Km vs. 11 Km and 360 mm vs. 800 mm, respectively). Total distance ran significantly decreased in each group to 0.9 Km and 2.2 Km, respectively, in mice at 28 months of age. All mice developed tumors. Tumor volume decreased in B6 mice from 4 months to 12 months to 450 mm and did not change with increasing age. Tumor volume in CB6 F1 mice remained constant at about 350 mm at all ages. In conclusion, CB6 F1 mice are more inclined to be physically active at a young age but less physically active at an old age compared to B6 mice, suggesting that running at a young age is not a predictor of physical aptitude for aging. Aging was not associated with increased tumor volume suggesting that non-genetic factors may be involved in the increased cancer incidence seen with increasing age. The aptitude for running may be associated with decreased tumor growth in young mice but not old mice. These preliminary data provide insight into the biological relevance of physiological assessment procedures in mice to help determine valid areas of focus in clinical trials of aging intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-107. doi:1538-7445.AM2012-LB-107