The Burden of Somatic Mutation with Age

Mutational damage occurs constantly to nuclear DNA throughout life. Little of that damage goes unrepaired, and little of the lasting breakage occurs in active parts of the genome. Where mutations go unrepaired in active parts of the genome, little of that occurs in important genes. Where it does occur in important genes, that only matters to the extent that (a) the mutation can spread, and (b) the mutation is potentially cancerous. Comparatively few cells in the body have the capacity to create many descendant cells through replication, as the Hayflick limit ensures that near all cells are limited in the number of times they can divide. The cell population of most tissues turns over with time, removing mutations. Nonetheless, mutations in precursor cell and stem cell populations, responsible for generating new somatic cells to support a given tissue, can lead to patchwork patterns of those mutations spread throughout the tissue. This is known as somatic mosaicism, and it most likely makes some contribution to both cancer risk and altered tissue function with age. Beyond this, a more recent suggestion is that double strand breaks, regardless of where in the genome they occur, can deplete cellular resources in ways that provoke epigenetic changes characteristic of aging. This work needs replication and greater support, but it would provide a convenient way to directly link mutation rate with contributions to degenerative aging, explaining many of the observations ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs