Cellular mechanisms for diminished scarring with aging

The study of an age-dependent spectrum of scar formation is driven by the d esire to understand and recapitulate scarless healing. Although focus in th e past has been directed toward scarring in the fetus, less exuberant scarr ing is a common clinical observation in the elderly. Cell turnover is a maj or contributor to the development of scar tissue and is governed by the pro liferative and apoptotic cellular fractions within a healing wound. We hypo thesize that the balance between cell proliferation and apoptosis during la te stages of excisional wound healing is, at least in part, responsible for age-related variations in scarring potential. Full-thickness 7-mm ulcers (four per ear), exposing bare cartilage, were ma de on the inner surface of the ear on 12 young and 12 aged New Zealand Whit e rabbits. Analyses were performed at days 15, 21, and 28 post-wounding. A previously described Scar Elevation Index was derived from histomorphometri c analysis, along with the quantification of epithelial ingrowth and total cellularity. Apoptotic cellular fractions were derived from TdT-mediated dU TP nick end-labeling assay-stained histologic sections; proliferative fract ions were derived from proliferating cell nuclear antigen-labeled serial se ctions. Young rabbits demonstrated significantly greater scar elevation/area. Apopt osis was strongly associated with progress of epithelialization in both gro ups. Significantly higher proliferative indices were seen in the young and were sustained through day 28, by which rime levels had substantially decli ned in the aged, No differences in apoptotic indices were demonstrated betw een groups at any time point. The clinical observation of less exuberant scarring with aging is supported by this animal model. Apoptosis follows the progression of epithelializati on but does not appear to independently influence scar morphology. A dimini shed proliferative response during later stages of healing is an important contributing mechanism for the decrease in scar formation seen in the elder ly.