The Mitochondrial Theory of Ageing

Carol A. Allen, Mark van der Giezen and John F. Allen 

It is not known how much of the oxygen consumption of the cell is turned over to generating reactive oxygen species, but the figure is thought to be between 2% (Chance et al. 1979) and 0.2% (St-Pierre et al. 2002 Staniek and Nohl 2000). The cell has very efficient scavenging mechanisms, and so these figures may be underestimates. 

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The Mitochondrial Theory of Aging Involvement of Mitochondrial DNA Damage and Repair... 

As discussed previously, the mitochondrial theory of ageing rests on the observation that mitochondrial DNA is exposed to high levels of reactive oxygen species when the mitochondrion is performing its redox chemistry. These reactive oxygen species cause mutation. These mutations accumulate, gradually damaging the mitochondrion s ability to function. This happens in... 

Allen JF (1996) Separate sexes and the mitochondrial theory of ageing. J Theor Biol 180 135-140 Allen JF (2003) The function of genomes in bioenergetic organelles. Philos Trans Roy Soc Lond B Biol Sci 358 19-38... 

The mitochondrial theory of ageing was first proposed by Denham Harman, author of the free-radical theory, as a refinement of his original... 

Allen, J. F. Separate sexes and the mitochondrial theory of ageing. Journal of Theoretical Biology 180 135-140 1996. 

Recent development of mitochondrial theory of aging is so-called reductive hotspot hypothesis. De Grey [465] proposed that the cells with suppressed oxidative phosphorylation survive by reducing dioxygen at the plasma membrane rather than at the mitochondrial inner membrane. Plasma membrane redox system is apparently an origin of the conversion of superoxide into hydroxyl and peroxyl radicals and LDL oxidation. Morre et al. [466] suggested that plasma membrane oxidoreductase links the accumulation of lesions in mitochondrial DNA to the formation of reactive oxygen species on the cell surface. 

It is remarkable that the" catastrophic mitochondrial theory of aging" was proposed before the first pathogenic mutations in mtDNA had ever been described and it has been strengthened ever since. 

B. (2008) The mitochondrial free radical theory of ageing-where do we stand Front. Biosci., 13, 6554-6579. 

Miquel, J. An update on the oxygen stress-mitochondrial mutation theory of aging genetic and evolutionary implications. Experimental Gerontology 33 113-126 1998. 

Brunk UT, Terman A. (2002) The mitochondrial-lysosomal axis theory of aging accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269(8), 1996-2002. 

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