Age-dependent increase in deleted mitochondrial DNA in the human heart: Possible contributory factor to presbycardia

Hattori, Kazuki; Tanaka, Masashi; Sugiyama, Satoru; Obayashi, Toshihiro; Itō, Takayuki; Satake, Tatsuo; Hanaki, Yoshihiro; Asai, Junpei; Nagano, Makoto; Ozawa, Takayuki

doi:10.1016/0002-8703(91)90020-i

Cited by 251 publications

(86 citation statements)

References 17 publications

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“…We reported earlier that levels of mtDNA4977 increase at least 100-fold with age in human heart and brain tissue in individuals without heart or neurological disease (5). Studies by other groups have also shown that mtDNA deletions increase with age in heart muscle (21,22). In the current study, levels of the mtDNA4977 deletion mutation in many additional human tissues were assayed to gain insight into the cellular forces that influence the accumulation of mitochondrial deletions.…”

mentioning

confidence: 86%

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.

Cortopassi

Shibata

Soong

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

567

291

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An assay that selectively amplifes a specific deletion ofthe 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.

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mentioning

confidence: 86%

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.

Cortopassi

Shibata

Soong

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

567

291

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“…Levels of reactive oxygen species (ROS) increase in essentially all tissues during aging [7,27,28], and mitochondrial DNA deletions, consequences of ROS action, also accumulate progressively [4,29]. Such biochemical findings are extended by genetic and molecular biological evidence.…”

Section: Introductionmentioning

confidence: 99%

Oxidative imbalance in the aging inner ear

Jiang

Talaska

Schacht

et al. 2007

Neurobiology of Aging

177

122

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The mammalian inner ear loses its sensory cells with advancing age, accompanied by a functional decrease in balance and hearing. This study investigates oxidant stress in the cochlea of aging male CBA/J mice. Glutathione-conjugated proteins, markers of H 2 O 2 -mediated oxidation, began to increase at 12 months of age; 4-hydroxynonenal and 3-nitrotyrosine, products of hydroxyl radical and peroxynitrite action, respectively, were elevated by 18 months. Immunoreactivity to these markers was stronger in the supporting cells (Deiters and pillar cells) than the sensory cells. It appeared later (23 months) in the nerve fibers of the spiral ganglion and in the stria vascularis and spiral ligament. Conversely, antioxidant proteins (AIF) and enzymes (SOD2) decreased by 18 months in the organ of Corti (including the sensory cells) and nerve fibers but not in the stria vascularis. These results suggest the presence of different reactive oxygen species and differential time courses of oxidative changes in individual tissues of the aging cochlea. An imbalance of redox status may be a component of age-related hearing loss.

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“…Hattori et al, 1991;Cortopassi et al, 1992;Melov et al, 1995). However, over the course of the last decade the non-coding region of mtDNA has been preferred for studies on heteroplasmy distribution (e.g.…”

Section: Discussionmentioning

confidence: 99%

The link between mitochondrial DNA hypervariable segment I heteroplasmy and ageing among genetically unrelated Latvians

Pliss

Brakmanis

Ranka

et al. 2011

Experimental Gerontology

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To cite this version:This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractVarious studies have demonstrated that mitochondrial DNA (mtDNA) heteroplasmy tends to increase with age and that the observed frequency of heteroplasmy among populations mostly depends on the way it is measured. Therefore, we investigated age-related association on the presence of mtDNA heteroplasmy within the hypervariable segment 1 (HVS-I) in a selected study group. The study group consisted of 300 maternally unrelated Latvians ranging in age from 18 to over 90 years. To determine the optimal method for mtDNA heteroplasmy detection, three The results indicate that heteroplasmy in HVS-I is relatively common and occurs in a broad spectrum of sites. The above is supported by evidence to eventual increase of the probability of heteroplasmy with age due to specific mitochondrial haplogroup background. Research HighlightsThe results indicate that heteroplasmy in HVS-I is relatively common and occurs in a broad spectrum of sites. Consequently, a strong association is found to exist between the mtDNA heteroplasmy and ageing in the studied population.We found that the Denaturing Gradient Gel Electrophoresis (DGGE) and the SURVEYOR TM Mutation Detection Kit assay exhibited a lower limit of detection (LOD) of mtDNA heteroplasmy and revealed the presence of heteroplasmy at the already existing 1% and 5% occurrence in the sample.

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Age-dependent increase in deleted mitochondrial DNA in the human heart: Possible contributory factor to presbycardia

Cited by 251 publications

References 17 publications

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues.

Oxidative imbalance in the aging inner ear

The link between mitochondrial DNA hypervariable segment I heteroplasmy and ageing among genetically unrelated Latvians

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