Aging-Dependent Large Accumulation of Point Mutations in the Human mtDNA Control Region for Replication

Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1999-10, Vol.286 (5440), p.774-779
Main Authors: Michikawa, Yuichi, Mazzucchelli, Franca, Bresolin, Nereo, Scarlato, Guglielmo, Attardi, Giuseppe
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Ageing, cell death
Aging
Aging (Biology)
Aging (Individuals)
Aging - genetics
Anatomy & physiology
Biological and medical sciences
Cell Line
Cell nucleus
Cell physiology
Cells
Child
Child, Preschool
Coding
Deoxyribonucleic acid
DNA
DNA Damage
DNA Repair
DNA Replication - genetics
DNA, Mitochondrial - biosynthesis
DNA, Mitochondrial - chemistry
DNA, Mitochondrial - genetics
Fetus
Fibroblasts
Fundamental and applied biological sciences. Psychology
Gels
Genetic mutation
Gerontology
Humans
Infant
Infant, Newborn
Longitudinal Studies
Middle Aged
Mitochondria - genetics
Mitochondrial DNA
Molecular and cellular biology
Molecules
Mutation
Mutation (Biology)
Nucleic Acid Conformation
Nucleic Acid Heteroduplexes
Plasmids
Point Mutation
Polymerase Chain Reaction
Pseudogenes
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Summary:Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.286.5440.774