Tumor suppressor dosage regulates stem cell dynamics during aging.

The ability of tissues to maintain homeostasis is dependent in part on the function of adult tissue stem cells, which have the capability to self-renew and differentiate into multiple lineages. It has been hypothesized that the ability of stem cells to maintain tissue homeostasis declines functionally with age and that this decline may account for many of the biological phenotypes associated with aging. Recently, tumor suppressors such as p53 have been implicated in both aging and the regulation of stem cell dynamics. Our recent findings suggest that p53 may impact hematopoietic stem cell (HSC) dynamics during mammalian aging. Utilizing mouse models of varying levels of p53 dosage, we have shown that alteration of p53 activity affects stem cell number, proliferation, and functionality with age. Several other recent studies have implicated other tumor suppressors in potential age-related regulation of HSC dynamics as well. These data support a model in which aging is caused in part by a decline in tissue stem cell regenerative function, regulated in part by tumor suppressors.