Evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24-91 years). The effect of plasma carotenoid concentrations, a group of dietary derived phytochemicals with potent antioxidant and anti-inflammatory properties, was also evaluated. CSF of participants aged >45 years contained increased levels of lipid peroxidation (F2-isoprostanes) (p=0.04) and inflammation (IL-6) (p=0.00) and decreased levels of both total antioxidant capacity (p=0.00) and NAD(H) (p=0.05), compared to their younger counterparts. After adjusting for age and gender, total antioxidant capacity correlated positively with both -carotene (p=0.01) and -carotene (p<0.001) in plasma. An inverse correlation was seen between plasma lycopene and the plasma inflammatory cytokine IL-6 (p=0.02). An increase in plasma -cryptoxanthin correlated with a decrease in CSF IL-6 (p=0.04). A significant positive correlation was found between plasma lycopene and both plasma (p<0.001) and CSF (p<0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein + zeaxanthin and markers of oxidative stress in the plasma or CSF. These data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be moderated by the consumption of specific dietary carotenoids.