Somatic Chromosomal Mosaicism as a Mechanism of Aging and Disease

Stochastic mutational damage to nuclear DNA occurs constantly in the body, and near all of it is quickly repaired. Most unrepaired damage occurs in DNA that isn't used, or the change has only has a small effect on cell metabolism, or occurs in a somatic cell that will replicate only a limited number of times. When mutations occur in stem cells or progenitor cells, however, they can spread widely through tissue, producing a pattern of mutations known as somatic mosaicism. It is thought that this can contribute to the progression of aging via a slowly growing disarray of cellular metabolism, particularly through the spread of more severe damage, such as aneuploidy, missing or additional chromosomes. That said, firm evidence for the size of this effect remains to be produced. Researchers here focus particularly on this more severe chromosomal mosaicism, rather than minor damage. Somatic chromosomal mosaicism is the presence of cell populations differing with respect to the chromosome complements (e.g. normal and abnormal) in an individual. Chromosomal mosaicism is associated with a wide spectrum of disease conditions and aging. This type of intercellular genomic variations is commonly associated with a wide spectrum of genetic diseases ranging from chromosomal syndromes to complex disorders, but dynamic changes of mosaicism rates produced by the accumulation of somatic mutations (i.e. aneuploidy) seem to be an important cytogenetic mechanism for human aging. Cyto...
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