Advances in biomedical research depend on animal experiments that investigate a variety of health interventions. A potential confounding problem with animal studies is that the typical way in which most research animals are housed results in extreme physical inactivity. The emerging field of inactivity physiology has provided theory and evidence that is compelling scientists to reassess the way in which laboratory animals are typically housed. The proposed study will address the hypothesis that animals with no access to exercise outside a standard cage (SED) will have gene expressions that are up (>1.4) or down (<0.7) regulated compared with animals that have regular access to exercise (EX) or intermittent physical activity (PA); that these gene expressions are associated with phenotypes including age-related diseases such as cardiovascular disease, tumor development, and dementia; and that gene expression differences among the groups will not occur at 3 months, instead will occur at 9 months, and that different phenotypes will occur at or after 9 months. We plan to 1) measure gene expression and specific proteins in cardiac tissue, hippocampus, and mammary tissue at 3 and 9 months and compare genotype and phenotype data with our 16 month data set to determine if animals with no access to physical activity demonstrate different gene expression levels and/or phenotypes compared with animals having access to intermittent physical activity or regular exercise. These experiments will 1) tell us when during the life span, key gene expression levels and specific proteins change due to access to physical activity or exercise; 2) compare phenotypes associated with these gene expressions (e.g. cardiovascular risk factors, tumor development, learning and memory) among the three experimental groups at different ages; and 3) determine the interaction of age and access to either no activity outside a cage, intermittent physical activity or regular exercise on health and disease over the typical life span of a laboratory rat. These results could significantly change strategies for designing animal experiments in long-term health and intervention research studies. [unreadable] [unreadable] [unreadable] [unreadable]