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|Title:||Roundtable discussion. How best to ameliorate the normal increase in mitochondrial superoxide formation with advancing age.|
|Epworth Authors:||Linnane, Anthony|
Ji, L. L.
Aiken, J. M.
Feuers, R. J.
Wei, Y. H.
Hipkiss, A. R.
Von Zglinicki, T.
Curtay, J. P.
Mitochondrial Superoxide Radical Production
Mitochondrial Superoxide Formation
Centre for Molecular Biology and Medicine, Epworth Medical Centre, Richmond, Victoria, Australia.
|Publisher:||New Yor Academy of Sciences|
|Citation:||Annals of the New York Academy of Sciences, Nov 1998; 854(1): 251-267|
|Abstract:||Aging is related to the rate of oxygen consumption. Over 90% of oxygen is used by the mitochondria; of this, 1 to 3% is diverted to superoxide radical formation. Although other sources of superoxide radicals (and H2O2) are present in the cell, their contribution should be small compared to that of the mitochondria. Mitochondrial‐derived superoxide radicals can produce mitochondrial DNA changes. These changes are reflected in the synthesis of defected respiratory chain components that further increase the rate of superoxide radical formation and decrease the rate of ATP production. The decline in mitochondrial function with time is believed to contribute to the progressive increase in the chance of disease and death with increasing age. Thus, decreasing the rate of mitochondrial superoxide radical formation should be a significant focus of efforts to increase the span of healthy, useful life. Today, mitochondrial superoxide radical production can be decreased by caloric restriction, and probably by nitrone and nitroso compounds‐if so, then also by nitroxides and hydroxylamines. Birds divert a smaller fraction of the O2 they use to the formation of superoxide radicals than do mammals; the same is true of the long‐lived white‐footed mouse compared to normal mice. Can means be found to do the same in humans? Another approach to the problem would be to search for compounds that can associate with electron‐rich areas of the respiratory chain‐possibly buckminsterfullerene and its derivatives (free radical sponges)‐so as to block access by O2 to these areas. Denham Harman|
|Journal Title:||Annals of the New York Academy of Sciences|
|Appears in Collections:||Pre-Clinical|
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