A Skeptical View of the Role of Nuclear DNA Damage in Aging

It is evident and settled that stochastic nuclear DNA damage contributes to cancer. The more of it that you have, the worse your risk. What is still very much debated is whether nuclear DNA damage contributes meaningfully to degenerative aging, and how it does so. Most mutational damage to DNA occurs in regions that are inactive, in cells that have comparatively few divisions remaining before reaching the Hayflick limit. Even if damage alters the function of such a cell, in some non-cancerous way, it is unclear as to how this could amount to a meaningful contribution to loss of tissue function. The one school of thought is focused on somatic mosaicism, the spread of mutations throughout a tissue when mutational damage occurs in stem cells. In this case subtle dysfunctions could accumulate and interact with the spread of mutated cells over time. While there is evidence for somatic mosaicism to contribute to the risk of some forms of cancer, evidence is still lacking for it to meaningfully affect tissue function to the degree that aging does. A second school of thought is focused on unexpected consequences of the repeated operation of DNA repair machinery. Double strand break repair can apparently deplete factors needed for maintaining the correct structure and epigenetic control of nuclear DNA, leading to age-related changes in epigenetics and gene expression. This is a comparatively recent discovery, and not yet fully digested, replicated, and risen to the stat...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs