The mitochondrial theory of aging: Is the culprit a faulty disposal systemrather than indigenous mitochondrial alterations?

Mitochondrial damage and the proportion of effete mitochondria in cells inc rease with age. According to the mitochondrial theory of aging, this phenom enon is mostly due to oxidative damage and is a major (and, some argue, the main) determinant of aging. It will be argued briefly that this phenomenon plays a role that is not exclusively crucial in aging. It will also be con tended, essentially on theoretical grounds (for lack of sufficient current information), that there is low probability that the accumulation of reduce d degradation of affected mitochondria is due to diminished production of h ydroxyl radicals, as suggested by Aubrey and de Grey (1997) and expanded by Kowald (in this issue). What seems more likely is that the phagolysosomal disposal system of effete mitochondria is considerably altered in cells of aging organisms. Also, in view of the significant role of damaged mitochond ria in the initial steps in apoptosis and the lack of evidence of massive a poptosis of cells in senescent individuals, the damage that exists may be m ilder than anticipated by the mitochondrial theory of aging. A brief fundam ental summary on the biology of mitochondria is included for the sake of be tter understanding the arguments presented in this article. Also, suggestio ns are made for experimental testing of the hypotheses presented by Aubrey and de Grey (1997) and Kowald (1999). (C) 1999 Elsevier Science Inc. All ri ghts reserved.