Better Characterizing the Clonal Expansion of Somatic Mutations in Aging Tissues

Mutational damage to nuclear DNA occurs constantly in all cells, and not all of it is successfully repaired. Setting aside recent evidence for cycles of damage and repair to cause epigenetic changes characteristic of aging, most unrepaired mutational damage has no meaningful consequence. It occurs in somatic cells that have few cell divisions left, so will not spread, and these cells will die or become senescent and be destroyed once they reach the Hayflick limit. It occurs in genes that are not active in the tissue in question, so even in long-lived somatic cells that do not replicate, such as those of the central nervous system, most mutations will be irrelevant to function. So how might this process significantly affect tissue function and health? Firstly, mutations or combinations of mutations to a small number of important genes can make a cell cancerous, leading to unfettered replication and a tumor if not stopped by the immune system. Secondly, mutations that take place in a stem cell or progenitor cell can spread widely into tissue, and if they happen to change function in some way, that might contribute to age-related decline. There is no good evidence for the size of this effect, however. A first step on the way towards gathering that evidence is mapping the extent of somatic mutation and its clonal expansion in aged tissues, a project that is still ongoing in the research community. Should somatic mutation turn out to be an important contributing caus...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs