While proliferation is decreased in aged tissues, no change in SC number was detected by our group or Bickenbachs. Lechler et al. examined types of SC divisions. Divisions perpendicular to the basement membrane were 8% in single-layered embryonic epidermis, 66% in multilayer epidermis and 85% in adult mice. In humans there is a decrease in cells positive for the proliferation marker Ki67. Our aim was to quantify mitoses of basal keratinocytes in vivo, and examine the types of division, over the human lifespan. We quantified divisions in the basal layer in neonatal (0-7 days), adult (30-45 years) and aged (70-80 years) skin. Asymmetric segregation of polarity proteins is a defining characteristic of SCs. We visualized division orientation in the basal layer using gtubulin (spindle) and NUMA (polarity protein) in biopsies. Because of the limited divisions seen in vivo, we also quantified division type in keratinocytes from freshly obtained biopsies, in vitro, using Numb segregation to identify asymmetric SC divisions. The number of divisions/10cm of basal layer was significantly decreased with age [neonatal 7.6AE2 (n¼5) vs. adult 3.2AE0.5 (n¼4) vs. aged 1.5AE 0.4 (n¼8), p¼0.001]. Both perpendicular (asymmetric) and parallel (symmetric) divisions were decreased with age. No significant change in the proportion of perpendicular (asymmetric) SC divisions was detected (neonatal 41.7AE14.4% vs. adult 27.5AE15.9% vs. aged 36.8AE8%). Similar results were found in vitro [neonatal 29.1AE7.4% (n¼11) vs. adult 32.2% (n¼ 2) vs. aged 31.2AE11.6% (n¼ 7)]. We conclude that epidermal basal cell divisions decrease over the human lifespan such that the number of divisions in 70+ year olds is 20% of that in neonates. However, the ratio of asymmetric/symmetric divisions remains unchanged. These findings could reflect a decrease in SC number, an increase in SC quiescence, and/or longer cell cycle duration in human epidermis.
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