Transit-amplifying cell frequency and cell cycle kinetics are altered in aged epidermis.
Aged epidermis is less proliferative than young, as exemplified by slower wound healing. However, it is not known whether quantitative and/or qualitative alterations in the stem and/or transit-amplifying (TA) compartments are responsible for the decreased proliferation. Earlier studies found a normal or decreased frequency of putative epidermal stem cells (EpiSCs) with aging. We show, using long-term repopulation in vivo and colony formation in vitro, that, although no significant difference was detected in EpiSC frequency with aging, TA cell frequency is increased. Moreover, aged TA cells persist longer, whereas their younger counterparts have already differentiated. Underlying the alteration in TA cell kinetics in the aged is an increase in the proportion of cycling keratinocytes, as well as an increase in cell cycle duration. In summary, although no significant difference in EpiSC frequency was found, TA cell frequency was increased (as measured by in vivo repopulation, growth fraction, and colony formation). Furthermore, the proliferative capacity (cellular output) of individual aged EpiSCs and TA cells was decreased compared to that of young cells. Although longer cell cycle duration contributes to the decreased proliferative output from aged progenitors, the greater number of TA cells may be a compensatory mechanism tending to offset this deficit.
Charruyer
Alexandra
A
Department of Dermatology, University of California, San Francisco, California 94121, USA.
Barland
Chantal O
CO
Yue
Lili
L
Wessendorf
Heike B
HB
Lu
Ying
Y
Lawrence
H Jeffrey
HJ
Mancianti
Maria L
ML
Ghadially
Ruby
R
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D016196:S Phase / Q000502:physiology; D015595:Skin Aging / Q000473:pathology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
D049452:Green Fluorescent Proteins