Longer Genes May Be More Disrupted than Shorter Genes by Random DNA Damage Occuring with Age

Random mutational damage to nuclear DNA occurs constantly. While near all of it is restored by the highly efficient suite of DNA repair mechanisms present in the cell, some is not. This damage accumulates over time. Fortunately, near all of it occurs in DNA that is unused in that cell type, or occurs in genes that are not all that important, or occurs in somatic cells that have few replications remaining before hitting the Hayflick limit. In other words, most DNA damage isn't all that important, and even where it sticks, it will be cleared from the body via the normal processes of replacement of cells in a tissue. How does DNA damage contribute to aging? Firstly, cancer risk: an unlikely combination of mutations occurring in any cell can give rise to a cancerous cell capable of unfettered replication. It is a risk throughout life, but that risk grows as the immune system ages and as the aged, ever more inflammatory tissue environment becomes more hospitable to the growth of a nascent cancer. Beyond cancer, it is likely that damage to stem cells is the primary problem, as lingering mutations in stem cells can spread throughout tissues to form patterns of overlapping mutational damage called somatic mosaicism. A minor loss of function in one cell is not a disaster. A minor loss of function in half of an organ may be a meaningful contribution to degenerative aging. Is DNA damage really random in its effects on genes, however? Today's open access paper is one of a n...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs