The mechanisms controlling organismal aging have yet to be clearly defined. In our recent paper [1], we revealed thatTAp63, the p53 family member, is a critical gene in preventing organismal aging by controlling the maintenance of dermal and epidermal precursor and stem cells critical for wound healing and hair growth. In the absence of TAp63, dermal stem cells (skin-derived precursors or SKPs) in young mice are hyperproliferative. As early as one month of age, SKPs and epidermal precursor cells exhibit signs of premature aging including a marked increase in senescence, DNA damage, and genomic instability resulting in an exhaustion of these cells and an overall acceleration in aging. Here, we discuss our findings and its relevance to longevity, regenerative medicine, and tumorigenesis.