There is strong evidence showing that aging is associated with vascular oxidative stress, which has been causally linked to the development of cardiovascular diseases. NF-E2-related factor-2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals leading to the upregulation of various antioxidant genes. The present study was designed to elucidate age-related changes in the homeostatic role of Nrf2-driven free radical detoxification mechanisms in the vasculature. We found that in the aorta of Fischer 344 ϫ Brown Norway rats, aging results in a progressive increase in O 2 ·Ϫ production, and downregulates protein and mRNA expression of Nrf2, which is associated with a decreased nuclear Nrf2 activity and a decrease in the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, ␥-glutamylcysteine synthetase, and heme oxygenase-1. There was an inverse relationship between vascular expression of Nrf2 target genes and agerelated increases in the expression of the NF-B target genes ICAM-1 and IL-6, which was significant by regression analysis. In cultured aorta segments of young (3 mo old) rats treatment with H 2O2 and high glucose significantly increases nuclear translocation of Nrf2 and upregulates the expression of Nrf2 target genes. In contrast, in cultured aorta segments of aged (24 mo old) rats, the induction of Nrf2-dependent responses by H 2O2 and high glucose are blunted. High glucose-induced vascular oxidative stress was more severe in aortas of aged rats, as shown by the significantly increased H 2O2 production in these vessels, compared with responses obtained in aortas from young rats. Moreover, we found that aging progressively increases vascular sensitivity to the proapoptotic effects of H 2O2 and high glucose treatments. Taken together, aging is associated with Nrf2 dysfunction in the vasculature, which likely exacerbates age-related cellular oxidative stress and increases sensitivity of aged vessels to oxidative stressinduced cellular damage.senescence; apoptosis; oxidative stress resistance; vascular injury THE OXIDATIVE STRESS THEORY of aging postulates that increased production of reactive oxygen species (ROS) with age induces a variety of macromolecular oxidative modifications and that accumulation of such oxidative damage is a major causal factor in organismic senescence. Although there is currently much debate over the importance of increased cellular oxidative stress in regulation of life span (4, 29), there is a consensus that increased ROS levels importantly contribute to the development of age-associated diseases (68). There is strong evidence that oxidative stress develops with age in the arterial system both in humans (19 -21, 25, 28) and laboratory animals (16,24,26,44,61). Increased production of ROS in the aged vasculature results in endothelial dysfunction and promotes the development of atherosclerotic vascular diseases (including myocardial infarction, stroke, vascular dementia), which are responsible for the majority of agerelate...

Collisions of Au on Au at incident energies of 150, 250 and 400 A MeV were studied with the FOPI-facility at GSI Darmstadt. Nuclear charge (Z ≤ 15) and velocity of the products were detected with full azimuthal acceptance at laboratory angles 1 • ≤ θ lab ≤ 30 • . Isotope separated light charged particles were measured with movable multiple telescopes in an angular range of 6 − 90 • . Central collisions representing about 1% of the reaction cross section were selected by requiring high total transverse energy, but vanishing sideflow. The velocity space distributions and yields of the emitted fragments are reported. The data are analysed in terms of a thermal model including radial flow. A comparison with predictions of the Quantum Molecular Model is presented.PACS: 25.70.Pq

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