In addition, aged mice showed increased expression of several elements of the complement system including complement component 4A , C4B, C3, and C1q, which facilitate phagocytosis of cells or bacteria through opsonization. C1q binds to neurons as they have low expression of complement resistant molecules such as DAF and CD59. This raises the possibility that neurons in the aged brain may be at greater risk of destruction through C1q labeling. Additionally, increased expression of C1, C3 and C4 mRNA has been found in the brains of Alzheimer patients, and is thought to contribute to the progression of Alzheimer��s disease by inducing microglia activation and proinflammatory cytokine release. Collectively, these NVP-BEZ235 age-related changes in neuroinflammation may contribute to the increased vulnerability to age-related cognitive decline and the progression of neurodegenerative diseases. Exercise may offer neuroprotection through regulating aspects of immune activity. Prior studies have found that exercise in adult subjects increases expression of anti-inflammatory molecules while reducing inflammatory mediators. Our data show that wheel running reduced expression of C4B which is released from microglia following an immune stimulus. Additionally, wheel running enhanced expression of shadow of a prion protein , a gene that encodes for the protein Sho that has neuroprotective-like effects against infection with a prion. SPRN expression was reduced in the aged mice, but was elevated in response to exercise. Though more work is needed to fully elucidate the ability of exercise to attenuate neuroinflammation, particularly in aged subjects, these data provide NSC 136476 clinical trial evidence that exercise may afford some protection by modulating immune activity within the brain. The trophic factor, insulin-like growth factor , plays a complex role in the aging process. Research on age-related 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.