Cellular mechanisms for diminished scarring with aging

The study of an age-dependent spectrum of scar formation is driven by the desire to understand and recapitulate scarless healing. Although focus in the past has been directed toward scarring in the fetus, less exuberant scarring is a common clinical observation in the elderly. Cell turnover is a major contributor to the development of scar tissue and is governed by the proliferative and apoptotic cellular fractions within a healing wound. We hypothesize that the balance between cell proliferation and apoptosis during late 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 made on the inner surface of the ear on 12 young and 12 aged New Zealand White rabbits. Analyses were performed at days 15, 21, and 28 postwounding. A previously described Scar Elevation Index was derived from histomorphometric analysis, along with the quantification of epithelial ingrowth and total cellularity. Apoptotic cellular fractions were derived from TdT-mediated dUTP nick end-labeling assay-stained histologic sections; proliferative fractions were derived from proliferating cell nuclear antigen-labeled serial sections. Young rabbits demonstrated significantly greater scar elevation/area. Apoptosis was strongly associated with progress of epithelialization in both groups. Significantly higher proliferative indices were seen in the young and were sustained through day 28, by which time levels had substantially declined in the aged. No differences in apoptotic indices were demonstrated between 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 epithelialization but does not appear to independently influence scar morphology. A diminished proliferative response during later stages of healing is an important contributing mechanism for the decrease in scar formation seen in the elderly.