Changes in stem cell self-renewal in aging epidermis

In the epidermis, stem cells in the basal layer of the epidermis undergo self-renewal and\ud differentiation to support the maintenance of the suprabasal epidermal layers. When\ud aged versus young murine keratinocytes were transplanted into young hosts, no\ud significant difference in the number of epidermal stem cells was found. The number of\ud more differentiated progenitors (transit amplifying cells) was increased in aged skin.\ud Finally, the number of cells produced by individual aged epidermal stem cells and transit\ud amplifying cells was decreased compared to that of young cells.\ud To better understand the mechanisms of aging, we examined whether the number of\ud epidermal stem cells and/or their proliferative ability was decreased in comparison to\ud young epidermal stem cells, when transplanted into age-matched hosts. We also\ud examined whether there was an increased rate of self-renewal divisions in aged mice, as\ud has been previously predicted. For these studies, we used long-term repopulation assay\ud in-vivo to determine the number of cysts and their proliferative output. Then by culturing\ud cells in Nocodazole to arrest mitosis, we determined whether there is an alteration in\ud self-renewal division with aging.\ud When aged keratinocytes were transplanted into aged hosts, there were fewer long-term\ud epidermal proliferation units and each aged epidermal stem cell produced fewer cells\ud compared to young. When mitotic divisions in keratinocytes from aged and young were\ud arrested and studied an increase in asymmetric self-renewal divisions with aging was\ud found.These studies indicate that aged skin has fewer stem cells and that aged\ud epidermal stem cells are less proliferative than young. The increase in asymmetric\ud divisions in aged mice indicates that aged keratinocytes are self-renewing more often\ud and this may compensate for the slower cell cycle duration and the resulting decreased\ud output from each stem cell