Mutation

There is ample evidence that mutations are causally related to cancer, a prominent age-related disease. Since the 1950s the accumulation of spontaneous mutations in the DNA of organs and tissues has been hypothesized to underlie aging itself (e.g., Failla, 1958). What are mutations, and why are they there? First, it is necessary to distinguish DNA mutations from DNA damage. DNA damage consists of chemical alterations in DNA structure, leading to a structure that can no longer serve as a substrate for faithful replication or transcription. DNA damage cannot be copied to end up in daughter cells. DNA mutations are heritable changes in a DNA sequence of an organism, which can be part of a gene, a gene regulatory region, or some noncoding part of the genome. Mutations are usually introduced as a consequence of misreplication or misrepair, for example, due to the presence of DNA damage. Hence, DNA damage can lead to mutations when it is not correctly repaired. Mutations can vary from point mutations, involving single or very few base pairs to large deletions, insertions, duplications, and inversions. In organisms with multiple chromosomes, DNA from one chromosome can be joined to another and the actual chromosome number can be affected.

Mutations are inevitable. Indeed, they fuel the survival of cells and organisms in times of stress. They are the substrate for evolution, which gave rise to different life forms. In both prokaryotic and eukaryotic cells mutation rate can be greatly increased, causing many cells to die but also giving rise to cells with the necessary attributes to survive and expand. Cancer cells, for example, can undergo mutations in genes that control the mutation rate (for example, genes involved in DNA repair). Such "mutator phenotypes" allow them to accelerate the acquisition of novel attributes (e.g., drug resistance, tissue invasivity) through gene mutation. While in such cases mutations are detrimental for the host, they are beneficial for the cell. In most cases, mutations will have adverse effects on both the host and the cell. In the somatic cells of multicellular organisms, however, mutations usually have adverse effects.