Towards a Better Understanding of Clonal Hematopoiesis of Indeterminate Potential

Somatic mosaicism arises from random mutational damage to stem cells and progenitor cells. Daughter somatic cells resulting from mutated cells also bear these mutations, and so a pattern of differently mutated somatic cell populations spreads throughout a tissue over years and decades. This is thought to be a mechanism by which nuclear DNA damage can give rise to some meaningful degree of dysfunction beyond cancer risk. Otherwise, one must accept that near all mutations (a) affect few cells, as somatic cells are limited in their ability to replicate, and (b) occur in cells that will be destroyed on some timescale, as they hit the Hayflick limit. Further, the vast majority of somatic cell mutations occur in unused areas of DNA, and should not change cell behavior via altered or missing proteins. Recently, researchers have suggested that some forms of nuclear DNA damage cause characteristic age-related changes in gene expression regardless of where they occur and whether they are successfully repaired, which may turn out to be the more important issue deriving from DNA damage. With regard to changes that do affect cell function and then spread from stem cells into a sizable fraction of cells in a tissue, evidence is sparse when it comes to clear connections between this somatic mosaicism and specific issues in aging, however. That said, clonal hematopoiesis of indeterminate potential (CHIP) is a form of somatic mosaicism specific to the immune system, and one of the few ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs