Programmed cell death as a target to interrupt the aging program

Abstract

There are two opposite points of view on aging of organisms. The traditional concept assumes that aging is a stochastic process consisting in age-dependent accumulation of random injuries in living systems. However, many pieces of evidence are recently obtained in favor of an alternative scheme suggesting that aging is genetically programmed being the final step of ontogenesis. The latter concept predicts (i) the existence of non-aging species which have lost the aging program and (ii) that the program in question can be experimentally interrupted by manipulations with corresponding genes or by small molecules operating as inhibitors of the execution of aging program. In this paper we summarize observations which are consistent with these two 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). We argue 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 of aging program. A pharmacological approach to switch off the aging program is considered, and this approach involves mitochondria-targeted antioxidants and uncouplers. Such compounds prevent mitochondrial oxidative stress which increases with age and stimulates the age-dependent apoptosis.

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Correspondence to V. P. Skulachev.

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Original Russian Text © F.F. Severin, V.P. Skulachev, 2009, published in Uspekhi Gerontologii, 2009, Vol. 22, No. 1, pp. 37–48.

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Severin, F.F., Skulachev, V.P. Programmed cell death as a target to interrupt the aging program. Adv Gerontol 1, 16–27 (2011). https://doi.org/10.1134/S2079057011010139

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Keywords

  • apoptosis
  • aging
  • mitochondria-targeted antioxidants