[Programmed cell death as a target to interrupt the aging program].
There are two opposite points of view on aging of organisms. The canonic concept assumes that aging is a stochastic process consisting in age-dependent accumulation of occasional injuries in living systems. However, many pieces of evidence are recently obtained in favor of the alternative scheme suggesting that aging is genetically programmed being the final step of ontogenesis. The latter concept predicts that (i) non-aging species should exist who has lost the aging program and (ii) the program in question can experimentally be interrupted by manipulating with corresponding genes or by low molecules operating as inhibitors of execution of aging program. In this paper, we summarize observations which are consistent with two above predictions. In both cases, interruption of the aging program is based upon inhibition of programmed cell death (apoptosis) mediated by mitochondrial reactive oxygen species (ROS). It is stated that the main difference between young and old multicellular organisms consists in the cellularity, i. e. in number of functional cells in organs or tissues rather than in quality of these cells. The cellularity decreases due to domination of apoptosis over proliferation in aging organisms. This means that apoptosis appears to be the basis for aging program. A pharmacological approach to switch off the aging program is considered, which is used mitochondria-targeted antioxidants and uncouplers. Such compounds prevent mitochondrial oxidative stress increasing with age and stimulating the age-dependent apoptosis.
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Skulachev
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D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000502:physiology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology; D016678:Genome; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D009154:Mutation; D010101:Oxygen Consumption / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species