Delayed cutaneous wound healing in young and old female mice is associated with differential growth factor release...

The capacity for tissue repair during wound healing declines with age. A chronic low but systemic inflammatory status, often called "inflammaging", is considered a key factor that contributes to impaired tissue regeneration. This phenomenon has been substantiated by an increased number of immune cells in wound-tissue of old mice. Although immune cells coordinate an inflammatory response by their secretome the composition of the wound milieu has not been examined. In young (2 months) and old (18 months) female mice, excision wounds were induced using a punch biopsy device, i.e., the healing progress occurred through secondary intention. The closure rate was analyzed for 7 days. At days 1, 3 and 7 post-surgery, wound specimen were investigated for immunohistochemical detection of granulocytes, M1-macrophages and mesenchymal stem cells of the skin. The concentrations of inflammatory cytokines and regenerative growth factors were determined in tissue homogenates by ELISA. The carbonyl assay was used to determine protein oxidation. In old mice, the wound closure was delayed between days 1 and 3 post-surgery, as was the peak of immune cell infiltration. There was no age effect on the concentration of inflammatory cytokines, but wounds of young animals contained higher number of mesenchymal stem cells and increased levels of growth factors. Protein oxidation was increased with age. The present study suggests that a reduced regenerative capacity rather than an enhanced inflammatory score affected the tissue regeneration process in old mice.