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Aging-dependent Large Accumulation Of Point Mutations In The Human MtDNA Control Region For Replication.
Y. Michikawa, F. Mazzucchelli, N. Bresolin, G. Scarlato, G. Attardi
Published 1999 · Biology, Medicine
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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.
This paper references
In organello footprint analysis of human mitochondrial DNA: human mitochondrial transcription factor A interactions at the origin of replication.
S. C. Ghivizzani (1994)
Progressive Increase of the Mutated Mitochondrial DNA Fraction in Kearns-Sayre Syndrome
N. Larsson (1990)
Homopolymeric tract heteroplasmy in mtDNA from tissues and single oocytes: support for a genetic bottleneck.
D. Marchington (1997)
Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy.
M. Yoneda (1992)
Animal mitochondrial DNA: an extreme example of genetic economy.
G. Attardi (1985)
Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA.
Julio Montoya (1982)
Is cell aging caused by respiration-dependent injury to the mitochondrial genome?
J. Fleming (1982)
The mutagenesis proteins UmuD' and UmuC prevent lethal frameshifts while increasing base substitution mutations.
N. Reuven (1998)
Mosaicism for a specific somatic mitochondrial DNA mutation in adult human brain
N. W. Soong (1992)
Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation.
M. P. King (1989)
Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging.
Francesco Pallotti (1996)
Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: Evidence for an increased frequency of deletions/additions with aging
L. Pikó (1988)
Oxidative damage and mitochondrial decay in aging.
M. Shigenaga (1994)
RNase mitochondrial RNA processing correctly cleaves a novel R loop at the mitochondrial DNA leading-strand origin of replication.
D. Y. Lee (1997)
DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein.
R. P. Fisher (1992)
Sequence and organization of the human mitochondrial genome
S. Anderson (1981)
Population variation of human mtDNA control region sequences detected by enzymatic amplification and sequence-specific oligonucleotide probes.
M. Stoneking (1991)
Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts.
M. Hayakawa (1992)
Somatic mutations of the mitochondrial genome in human colorectal tumours
K. Polyak (1998)
Sequence and properties of the human KB cell and mouse L cell D-loop regions of mitochondrial DNA.
M. W. Walberg (1981)
Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA.
B. Greenberg (1983)
Comprehensive, rapid and sensitive detection of sequence variants of human mitochondrial tRNA genes.
Y. Michikawa (1997)
MITOCHONDRIAL DNA MUTATIONS AS AN IMPORTANT CONTRIBUTOR TO AGEING AND DEGENERATIVE DISEASES
AnthonyW. Linnane (1989)
Human brain contains high levels of heteroplasmy in the noncoding regions of mitochondrial DNA.
E. Jazin (1996)
Length heterogeneity of a conserved displacement-loop sequence in human mitochondrial DNA.
W. Hauswirth (1985)
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N. Bianchi (2001)
A novel method for estimating substitution rate variation among sites in a large dataset of homologous DNA sequences.
G. Pesole (2001)
Maintenance of mitochondrial DNA integrity: repair and degradation
D. Kang (2002)
Aging impact on biochemical activities and gene expression of Drosophila melanogaster mitochondria.
P. Dubessay (2007)
Toward a control theory analysis of aging.
M. Murphy (2008)
Mitochondrial DNA alterations and reduced mitochondrial function in aging
Sadie L. Hebert (2010)
Association of mtDNA D-Loop Polymorphisms with Risk of Gastric Cancer in Chinese Population
L. Wei (2011)
The mitochondrial free radical theory of ageing--where do we stand?
J. Gruber (2008)
Blood mitochondrial DNA mutations in HIV-infected women and their infants exposed to highly active antiretroviral therapy during pregnancy
Marissa H. J. Jitratkosola (2012)
Effect of Treating Induced Mitochondrial Damage on Embryonic Development and Epigenesis
T. Takeuchi (2005)
Mitochondrial DNA mutations and oxidative stress in mitochondrial diseases.
Y. Wei (2003)
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
D. Chan (2006)
Compromised respiratory adaptation and thermoregulation in aging and age-related diseases
Sic L. Chan (2010)
Heteroplasmic mitochondrial DNA mutations in normal and tumor cells
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Frank J. Castora (2019)
N. Mori (2015)
Mitochondrial dysfunction in aging: Much progress but many unresolved questions
B. A. Payne (2015)
Mitochondrial DNA Repair
S. Martin (2011)
The Role of Mitochondria in Brain Aging and the Effects of Melatonin
G. Escames (2010)
Physical characteristics of an individual: The identification of biomarkers for biological age determination
Michelle Stefaniw-Alvarez (2007)
OxPhos Defects and Their Role in Cancer Initiation and Progression
N. Yadava (2013)
Resistance of Mitochondrial DNA-depleted Cells against Cell Death
S. Park (2004)
Oxidative damage to mitochondria and aging
H. Remmen (2001)
Mitochondria and ageing in Drosophila
Geneviève Morrow (2008)
Aging and photoaging.
J. Chung (2003)
Mitochondrial DNA mutations in the haematopoietic system
R. Taylor (2004)
Energy metabolism of the visual system.
M. Wong-Riley (2010)
Mitochondrial DNA mutations. Brain developmental and ageing consequences, and possible treatments
Jaime M Ross (2012)
Mitochondrial genome maintenance in health and disease.
W. Copeland (2014)
Tissue-specific implications of mitochondrial alterations in aging.
Danhui Liu (2013)
Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutations
Y. Kraytsberg (2005)
Estimating age of humans based on telomere shortening.
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