Nature Genetics
2, 324 - 329 (1992)
doi:10.1038/ng1292-324
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced ageMarisol Corral-Debrinski1, Terzah Horton1, Marie T. Lott1, John M. Shoffner1, 2, M. Flint Beal3
& Douglas C. Wallace1, 2
1Departments of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA
2Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
3Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA We have examined the role of somatic mitochondrial DNA (mtDNA) mutations in human ageing by quantitating the accumulation of the common 4977 nucleotide pair (np) deletion (mtDNA4977) in the cortex, putamen and cerebellum. A significant increase in the mtDNA4977 deletion was seen in elderly individuals. In the cortex, the deleted to total mtDNA ratio ranged from 0.00023 to 0.012 in 67−77 year old brains and up to 0.034 in subjects over 80. In the putamen, the deletion level ranged from 0.0016 to 0.010 in 67 to 77 years old up to 0.12 in individuals over the age of 80. The cerebellum remained relatively devoid of mtDNA deletions. Similar changes were observed with a different 7436 np deletion. These changes suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing.
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