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Related Concept Videos

Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...

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Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase (COX/SDH) Double-labeling Histochemistry
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Region-specific changes in mitochondrial D-loop in aged rat CNS.

Simone C McInerny1, Amanda L Brown, Doug W Smith

  • 1Discipline of Anatomy, School of Biomedical Sciences, Faculty of Health and The Center for Brain and Mental Health Research, University of Newcastle, Callaghan, NSW 2308, Australia.

Mechanisms of Ageing and Development
|May 12, 2009
PubMed
Summary

Aging impairs mitochondrial function, potentially due to reduced mitochondrial DNA (mtDNA) replication and transcription. Studies show age-related declines in D-loop DNA and increases in common deletions in rat brain regions, suggesting impaired D-loop function contributes to aging.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Gerontology

Background:

  • Impaired mitochondrial oxidative phosphorylation (OXPHOS) is a hallmark of aging.
  • Reduced mitochondrial DNA (mtDNA) replication and transcription may underlie OXPHOS decline.
  • Alterations in the mtDNA displacement (D) loop or accumulation of mutations can affect mtDNA processes.

Purpose of the Study:

  • To investigate the age-related changes in the mtDNA D-loop and deletion mutations in specific regions of the Fischer 344 rat brain.
  • To correlate these molecular changes with the known age-related decline in OXPHOS.

Main Methods:

  • Analysis of D-loop (7S DNA) levels in spinal cord, medulla, midbrain, cerebellum, striatum, and cerebral cortex of young and aged Fischer 344 rats.
  • Quantification of common mtDNA deletion mutations in the same tissues.
  • Assessment of mitochondrial genome copy number across different brain regions and ages.

Main Results:

  • Significant age-related reductions in D-loop 7S DNA were observed in the striatum, cortex, and spinal cord.
  • An age-related and region-specific increase in the common deletion was detected, though it represented a small fraction of total mtDNA.
  • Mitochondrial genome copy number decreased by 18% with age in the whole brain, with regional variations.

Conclusions:

  • Age-related decline in OXPHOS may be linked to reduced D-loop function.
  • Specific mtDNA alterations, including D-loop changes and common deletions, occur in an age- and region-dependent manner in the rat brain.
  • These findings contribute to understanding the molecular mechanisms of aging in the central nervous system.