Region-specific changes in mitochondrial D-loop in aged rat CNS

Impaired mitochondrial oxidative phosphorylation (OXPHOS) is considered a cause of aging. A reduction in mitochondrial DNA (mtDNA) replication and/or transcription may contribute to this OXPHOS diminution. Impairments in the displacement (D) loop, or non-coding, region of the mitochondrial genome, o...

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Bibliographic Details
Published in:Mechanisms of ageing and development 2009-05, Vol.130 (5), p.343-349
Main Authors: McInerny, Simone C., Brown, Amanda L., Smith, Doug W.
Format: Article
Language:English
Subjects:
Age Factors
Aging - genetics
Aging - metabolism
Animals
Biological and medical sciences
Central Nervous System - metabolism
Central Nervous System - physiology
Development. Metamorphosis. Moult. Ageing
DNA, Mitochondrial - genetics
Fundamental and applied biological sciences. Psychology
Gene Dosage
Male
Mitochondrial genome deletions
Mitochondrial genome mutation Hypothesis of aging
Mitochondrial replication
Mitochondrial transcription
Oxidative Phosphorylation
Rats
Rats, Inbred F344
Real-time quantitative PCR
Sequence Deletion
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Impaired mitochondrial oxidative phosphorylation (OXPHOS) is considered a cause of aging. A reduction in mitochondrial DNA (mtDNA) replication and/or transcription may contribute to this OXPHOS diminution. Impairments in the displacement (D) loop, or non-coding, region of the mitochondrial genome, or accumulation of mtDNA mutations, may affect mtDNA replication and transcription. We determined the effects of age on the D-loop and on mtDNA deletion mutations in the spinal cord, medulla, midbrain, cerebellum, striatum, and cerebral cortex of Fischer 344 rats. D-loop, 7S DNA levels were reduced by 3-fold in striatum, 2.5-fold in cortex, and 2-fold in the spinal cord of older animals. We did not detect a population of mtDNA affected by the most prevalent known (ND4-containing) deletions, indicating they do not comprise a significant portion of total mtDNA. However, we detected an age-related and region-specific increase in the common deletion, which comprised 0.0003–0.0007% of total mtDNA. Mitochondrial genome copy number varied between regions, in addition to an overall 18% decrease with age across the whole brain. These results suggest the age-related decline in OXPHOS may be related to a reduction in D-loop function.
ISSN:0047-6374
1872-6216
DOI:10.1016/j.mad.2009.01.008