[Biological and gerontological significance of oxygen]

The phylogenetic "discovery" of oxygen as the terminal electron acceptor of respiration may be regarded as a prerequisite of the development to higher forms of life. The rationale for this assumption is based on the considerable higher energy gain associated with aerobic respiration which allowed to go new pathways in metabolism. However, oxygen constitutes both a benefit and a threat to living things because aerobic respiration involves the formation of dangerously reactive intermediates. These intermediates have been recognized to play a key role in many pathogenetic events and postulated to contribute to the biological process of aging. Organisms which have availed themselves of the benefit of aerobic respiration, developed a series of synergistic defenses against its danger. Perturbation of oxygen homeostasis occurs when formation of toxic oxygen intermediates exceeds the capacity of protective mechanisms. A sudden event which leads to such an imbalance may cause the manifestation of different types of maladies. Our own investigations on rat-heart mitochondria have indicated that aging is associated with a progressive loss in the capacity to balance the formation of toxic oxygen metabolites. Despite a clear induction, activities of protecting enzymes seem to be "swamped" by an age-dependent raise of steady state levels of dangerous oxygen intermediates. The resulting structural damage and functional impairment of mitochondria are discussed as the primary cause of cellular aging.