More On DNA Damage, Stem Cell Aging

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To what degree does accumulated DNA damage contribute to the aging of stem cells? (Versus, say, changes in their niche or other potential causes). From this freely available review paper: "Adult stem cells are extremely important in the long-term maintenance of tissues throughout life. They regenerate and renew tissues in response to damage and replace senescent terminally differentiated cells that no longer function. Oxidative stress, toxic byproducts, reduced mitochondrial function and external exposures all damage DNA through base modification or mis-incorporation and result in DNA damage. As in most cells, this damage may limit the survival of the stem cell population affecting tissue regeneration and even longevity. ... a number of human genetic abnormalities associated with aging, and those replicated in the mouse, suggest that loss of DNA repair may contribute to the aging process. This review will provide support for the argument that maintenance of the adult stem cell genome through robust DNA repair is fundamental in the prevention of aging and disease; furthermore, that failure of genomic maintenance is a leading cause of cancer, as well as senescence."

Link: http://nar.oxfordjournals.org/cgi/content/full/gkm1064v1