Mitochondrial DNA mutations in disease and ageing.
The chronological accumulation of mitochondrial DNA mutations has been proposed as a potential mechanism in the physiological processes of ageing and age-related disease. We discuss the evidence behind this theory and relate some of the ageing mitochondrial changes to mitochondrial DNA disorders. In particular, we describe the aggregation of cytochrome c oxidase-deficient cells in both skeletal muscle and the CNS in normal ageing as seen in the mitochondrial DNA disorders. These mitochondrial enzyme-deficient cells have been shown to occur in significant quantities in both muscle and CNS in patients with mitochondrial DNA disorders. In both ageing and mtDNA disorder muscle these cytochrome c-deficient fibres contain high levels of a single mutant strain of mitochondrial DNA. Whether these mutations are a primary or secondary event in the physiology of ageing remains to be determined.
Department of Neurology, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH.
D A
DA
Cottrell
E L
EL
Blakely
M A
MA
Johnson
G M
GM
Borthwick
P I
PI
Ince
D M
DM
Turnbull
D000375:Aging / Q000235:genetics*; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D004194:Disease; D003576:Electron Transport Complex IV / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008928:Mitochondria; D009154:Mutation
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV