The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24–deficient (Zmpste24−/−) mouse could serve as a model of senescent wound healing.Methods:
Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24−/− mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry.Results:
Zmpste24−/− mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24−/− wounds had decreased proliferation, increased 8-hydroxy-2′-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow–derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial.Conclusions:
The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24−/− progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.