The trophic factor, insulin-like growth factor , plays a complex role in the aging process. Research on age-related XAV939 Wnt/beta-catenin inhibitor Alterations in IGF levels in the brain has show inconsistent results, as some report a decrease whereas others fail to detect a difference. However, there is evidence to suggest that expression of the IGF type I receptor increases with age. Our findings confirm this result, as aged mice showed increased expression of IGFR1 in the hippocampus, and additionally show that wheel running reduced IGFR1 expression. The age-related increase in IGFR1 may occur in response to low IGF levels or may be a compensatory mechanism to overcome resistance or functional deficits in the receptor signaling cascade. Given that exercise increases expression of IGF , the exerciseinduced reduction in IGFR1 may result from stabilizing trophic support in the aged brain. Alterations in mitochondria function are a central theory of aging. Mitochondria are a primary energy source throughout the body and therefore a decline in their function disrupts normal cellular activity and could ultimately lead to cell death. In support, we observed that aged mice showed reduced expression of mitochondrial ribosomal protein 63 , which is known to aid in protein synthesis within mitochondria. Further, we observed that exercise increased expression of MRP63. This finding is in agreement with prior work that indicates some of the beneficial effects of exercise are mediated through its influence on mitochondria. In agreement with prior reports, wheel running significantly increased expression of brain derived neurotrophic factor in both adult and aged mice. BDNF is believed to mediate the beneficial effects of exercise on cell growth, proliferation, and possibly cognitive enhancements. In addition to BDNF, we observed that a GO term related to growth was significantly enriched from exercise. For example, wheel running was found to increase expression of poly polymerase 1 and RuvB-like protein 1 , genes involved in repairing damage to DNA and maintaining MLN4924 genomic stability. Exercise was found to suppress expression of BCL2 binding component 3 , a gene that can initiate apoptosis. These findings confirm that exercise independent of age supports brain health by initiating growth and protection against destructive events. Collectively, these data highlight transcriptional changes that may mediate the anti-aging effects of exercise. Our findings confirm prior microarray experiments that assessed gene transcription changes in response to exercise , aging , or exercise only in aged mice. Ultimately, our findings indicate that the beneficial effects of exercise likely result from changes in multiple pathways that may be restorative in aged subjects, but also act as a preventive measure in younger subjects. The data emphasize that effective anti-aging treatments need to combat a complex array of changes. Wheel running was found to regulate chromatin structure, cell growth, immune activity, and trophic factors opposing many of the age-related changes in these categories. Findings argue that the therapeutic effects of exercise likely results from its ability to modulate a broad range of processes that are altered by normal aging.