Mitochondrial and nuclear DNA-repair capacity of various brain regions in mouse is altered in an age-dependent manner

The role of Cockayne Syndrome group B (CSB) protein in base excision repair and aging

“…Within the last few years it has become evident, that the mtBER capacity in the brain is relatively low compared to other organs of the body and that the repair capacity varies between different brain regions (Imam et al, 2006). There also seems to be region specific differences in how dramatically the DNA repair capacity changes with age.…”

Mitochondrial DNA repair in aging and disease

“…This decline was attributed to a decreased expression of repair enzymes such as OGG1 and DNA pol γ (83). A very recent publication on age-dependent alterations in mitochondrial and nuclear BER activities in five brain regions of 6-month and 18-month old mice demonstrated a significant age-dependent decrease in uracil, 8-oxoG and 5-OH-C incision activities in mitochondria from all brain regions, whereas variable patterns of changes were seen in nuclei (84).…”

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

“…Yet, if most RNA lesions detected in the current study are a direct result of ribosomal and transfer RNA oxidation rather than messenger RNA, it would suggest that RNA repair mechanisms may exist. Unfortunately, while expression and associated activity of multiple substrate-specific DNA glycosylases involved in DNA base excision repair have been widely studied, few have focused on the repair of oxidative damage in RNA [15,[65][66][67][68]. However, it would be expected that oxidized RNA would not be tolerated under normal cellular…”

“…It is estimated that ~2% of total oxygen consumed by the cell is converted to superoxide radical during respiration [14]. Although superoxide can be detoxified to water by sequential activities of superoxide dismutase and glutathione peroxidase, in the presence of reduced transition metals (copper and iron) hydrogen peroxide can generate hydroxyl radicals via Fenton [15] and/or Haber-Weiss reactions [16]. Increased oxidative damage to mitochondrial DNA (mtDNA),(~10X levels observed in nuclear DNA (nDNA)) is attributed to the close proximity to ROS generation and a lack of protective histones [14,17] and may contribute to the decreased glucose consumption and depletion of cellular energy noted in the earliest stages of AD [18][19][20].…”