Abstract:
:The mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA-damaging oxygen radicals. In turn, this is proposed to result in the accumulation of further mtDNA mutations. Finally, a bioenergetic crisis leads to overt tissue dysfunction and degeneration. A substantial body of circumstantial evidence seems to support this idea. However, the extent of detectable mtDNA mutation is far less than can easily be reconciled to this hypothesis, unless it is assumed that a subset of cells with much higher than average mtDNA mutation load is systematically lost by apoptosis. A rigorous test of the hypothesis remains to be undertaken, but would require a direct manipulation of the rate of mtDNA mutagenesis, to test whether this could alter the kinetics of aging.
journal_name
Aging Celljournal_title
Aging cellauthors
Jacobs HTdoi
10.1046/j.1474-9728.2003.00032.xkeywords:
subject
Has Abstractpub_date
2003-02-01 00:00:00pages
11-7issue
1eissn
1474-9718issn
1474-9726journal_volume
2pub_type
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