A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.
An assay that selectively amplifies a specific deletion of the mitochondrial genome has been used to study the extent of the deletion's accumulation in a variety of human tissues. The deletion occurs at much higher levels in nervous and muscle tissues than in all other tissues studied. The variation in deletion level between the same tissues in different persons of similar age appears to be less than the variation among tissues within an individual. Tests for artifactual explanations of the level differences were each negative. Three cellular parameters that are correlated with the level of the deletion are identified. The preferential accumulation of deleterious mitochondrial mutations in a restricted subset of aging human tissues may compound deficiencies of function in those tissues that accrue with age.
Cortopassi
G A
GA
Molecular Biology Section and Medical Center, University of Southern California, Los Angeles 90089-1340.
Shibata
D
D
Soong
N W
NW
Arnheim
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods
D004272:DNA, Mitochondrial