Changes in DNA repair during aging

Abstract

DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old.

HSP72 depletion suppresses γH2AX activation by genotoxic stresses via p53/p21 signaling

“…However, although in fact senescent cells may have higher background level of gH2AX, they form significantly fewer foci in response to g-radiation . Furthermore, it is well known that DNA repair, including DSB repair, deteriorates with aging (Gorbunova et al, 2007). We suggest that at least partially this deterioration can be associated with inability of senescent cells to phosphorylate H2AX and form foci.…”

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

“…A number of studies indicate that BER undergoes agerelated changes in several tissues. These include decrease in the activity of the DNA glycosylases or pol β and reduction in the protein levels or expression of pol β or APE1 with age (reviewed in (Cabelof et al, 2006;Gorbunova et al, 2007)). Thus, a decline of BER function with age might contribute to the accumulation of oxidative DNA damage and mutations, and the onset of aging (reviewed in (Gorbunova et al, 2007)).…”

“…These include decrease in the activity of the DNA glycosylases or pol β and reduction in the protein levels or expression of pol β or APE1 with age (reviewed in (Cabelof et al, 2006;Gorbunova et al, 2007)). Thus, a decline of BER function with age might contribute to the accumulation of oxidative DNA damage and mutations, and the onset of aging (reviewed in (Gorbunova et al, 2007)). Although there is limited evidence linking the decrease in the amount and activities of these core BER proteins with premature aging, defects in several other factors that have auxiliary, nonessential functions in BER could also contribute significantly to premature aging characteristics.…”

The Assessment of Cytogenetic Indices of Chernobyl Power Plant Disaster Liquidators

“…It is known that cytogenetic disorders become more frequent with the age, intensifying the changes in the chromosome apparatus of lymphocytes [16].…”