Increased stem cell quiescence underlies the decreased proliferation in aged human epidermis

Summary: Abstract Body: There is a decrease in cell proliferation in the human epidermis with age. While in some tissues aging has been associated with a decrease in stem cell (SC) number, no decrease has been seen in the hematopoietic system and skin. In both mammary and epidermal SCs there is a decrease in asymmetric stem cell self-renewal with age (associated with decreased P53 expression), expected to result in a decrease of committed progenitors (transit-amplifying cells). To help account for the decreased proliferation with age, we hypothesized that aging is associated with an increase in keratinocyte SC quiescence (a decrease in the number of SCs actively dividing). Tissue sections from formalin-fixed paraffin-embedded human aged (81y, n=5) and adult (21-37, n=6) skin surgical discard samples were studied. P21, a CDK1 inhibitor, was used to indicate quiescence. Ki67, associated with the cell cycle, was used to indicate active/cycling SCs. Sections were incubated with anti-p21 antibody and anti-ki67 antibody and then analyzed under a fluorescence microscope. Cells that were cycling (Ki67+) in the basal layer were considered SCs or early CPs. Cells in the basal layer that were quiescent (P21+) were considered quiescent SCs. The number of quiescent (P21+) basal cells was increased in aged vs. adult (0.6±0.30 vs 0.19±0.12, P=.015). The number of actively cycling (Ki67+) basal cells was decreased in aged vs. adult (1.7±1.1 vs 3.9±1.9, P=.05). The total numbers of quiescent and cycling basal keratinocytes was unchanged (2.3±1.1 vs 4.1±1.9, NS). Our study demonstrates that the decrease in stem cell self-renewal in aged adult human epidermis is associated with an increase in quiescent SCs. Furthermore, this study did not detect a change in total SC number. A more granular understanding of the hypoproliferation of aging is key to developing therapeutics targeting aging keratinocytes and restoring skin homeostasis. Brooke Vittimberga¹, Nwamaka Ijeh¹, Brook H. Abegaze^{1, 2}, Jun Xu², T R. Parenteau¹, Ruby Ghadially^{1, 2} 1. Dermatology, University of California San Francisco, San Francisco, CA, United States. 2. Dermatology, San Francisco VA Health Care System, San Francisco, CA, United States. Stem Cell Biology, Tissue Regeneration and Wound Healing