"Oxygen supply" as modulator of aging processes: hypoxia and hyperoxia models for aging studies.

Cell growth is regulated by several factors, including oxygen supply, which influence cell metabolism. Aging is characterized by decreased oxygen supply to tissue, a reduction of tissue PO(2) and of the activity of several enzymes and metabolic factors. The oxygen-gradient diffusion at capillary tissue level is essential for the cellular survival, while the homeostasis of the oxygen in the arterial blood is mediated by reflexes sensitive to oxygen decrease and by release of several factors. Aging is correlated with a reduction of cells' oxygen supply concomitant to a parallel decrease in oxygen demand by tissues. Both chronic hypoxia or hyperoxia are considered as stresses. Indeed, in both conditions, free radical species, which damage structural and functional components of the membrane, are generated. ROS (reactive oxygen species) are physiological products of aerobic life and their accumulation affects aging. Because hypoxia per se modulates mitochondria activity, influencing oxygen consumption, hypoxia and aging could share some link. Moreover, the observation that in hypoxia or hyperoxia there is an accumulation of lipofucsine as a general reaction to stress is consistent with the accumulation of such components during aging. Correlation between hypoxia-hyperoxia and life-span remains open until we solve the question of how and why do cells sense oxygen. In other words, to better understand aging we need to know what O(2) species are being sensed by cells. In conclusion, hypoxia and hyperoxia represent an experimental model adequate for studying aging processes.