Reviewing the DNA Damage Response in Aging

Nuclear DNA damage is considered a contributing cause of aging, though at this stage the research community is still proposing and debating processes by which this damage might cause metabolic dysfunction throughout the body. Mutations to nuclear DNA evidently increase cancer risk, but setting this aside, how does random damage to random cells contribute to the declines of age? There are a few possibilities; firstly that the vast majority of nuclear DNA damage, occurring as it does in somatic cells, or in unusued portions of the genome, is irrelevant. Harms are done when mutations affecting function occur in stem cells and progenitor cells, allowing that mutation to spread widely throughout a tissue. The second possibility, more recently proposed, is that all nuclear DNA damage systemically affects cell function wherever it occurs in the genome, because the processes of DNA repair have the side-effect of causing epigenetic changes characteristic of aging. Thirdly, higher levels of mutational damage may generate a greater burden of cellular senescence. Relative effect sizes of these processes are an open question, and much more work must be done to confirm that they are relevant in each case. One important aspect of the ageing process is the accumulation of DNA damage through time. While containing the entire genetic information (except for mitochondria-encoded genes), the nuclear genome is constantly threatened by genotoxic insults, with an estimated frequency...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs