Mitochondrial and Nuclear DNA Oxidative Damage in Physiological and Pathological Aging

DNA Cell Biol. 2020 Aug;39(8):1410-1420. doi: 10.1089/dna.2019.5347. Epub 2020 Apr 21.

Abstract

Mitochondria play an important role in numerous processes, including energy generation, regulating ion homeostasis, and cell signaling. Mitochondria are also the main source of reactive oxygen species (ROS). Due to the oxidative environment within mitochondria, the macromolecules therein, for example, mtDNA, proteins, and lipids are more susceptible to sustaining damage. During aging, mitochondrial functions decline, partly as a result of an accumulation of mtDNA mutations, decreased mtDNA copy number and protein expression, and a reduction in oxidative capacity. The aim of this study was to summarize the knowledge on DNA oxidative damage in aging and age-related neurodegenerative diseases. It has been hypothesized that various ROS may play an important role not only in physiological senescence but also in the development of neurodegenerative diseases, for example, Alzheimer's disease and Parkinson's disease. Thus, mitochondria seem to be a potential target of novel treatments for neurodegenerative diseases.

Keywords: Alzheimer's disease; Parkinson's disease; ROS; aging; mitochondria; mtDNA; oxidative damage.

Publication types

  • Review

MeSH terms

  • Aging / genetics*
  • Cell Nucleus / genetics*
  • Cell Nucleus / pathology
  • DNA Damage / genetics
  • DNA, Mitochondrial / genetics
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / pathology
  • Oxidative Stress / genetics*
  • Reactive Oxygen Species / metabolism

Substances

  • DNA, Mitochondrial
  • Reactive Oxygen Species