73. Aging Mitigates Androgen-Induced Impairment of Dermal Repair

PURPOSE: Testosterone (T) disrupts skin repair by altering the balance between pro-inflammatory and anti-inflammatory phases of wound healing (WH). The geriatric population is rapidly growing and surgical repair is known to be slower with age. While our group has previously proven androgen-mediated hypertrophic scarring and inhibition of cutaneous WH, there is no data on how these effects interact with senescent repair processes. This study aims to explore the effects of T on WH using a rodent model. METHODS: Young (8 weeks) and old (22 months) C57BL/6 mice underwent gonadectomy, with half receiving bi-weekly testosterone cypionate dissolved in sesame oil (+2T), and the other half receiving only sesame oil (noT). Four 6 mm dorsal cutaneous wounds were created 14 days post-castration. Planimetric imaging was conducted on postoperative days (POD) 3 and 5. Two-thirds of the wound tissues were harvested on POD3 or 5 for single-cell suspension preparation and flow cytometry analysis. The remaining tissues were analyzed via Luminex assay, histology, and qPCR. RESULTS: Testosterone significantly impaired WH in young mice, but this effect was nonsignificant in aged counterparts, with the difference in WH rates between the noT and +2T groups disappearing in the aged cohort. On POD5, young mice showed a higher percentage of immune cells (CD45+) compared to aged mice, with a significant difference in the noT groups. Neutrophil counts were similar between groups, but macrophage density was significantly higher in young mice. CD301b+ macrophages were significantly elevated in +2T young mice compared to noT, but this increase was much smaller in aged mice (2.5-fold versus 1.6-fold) where it did not reach significance. CONCLUSION: Testosterone negatively impacts WH in young mice but not in aged mice. Age-related repair dysfunction has been linked to either a diminished inflammatory response and persistent low-level inflammation. We hypothesize that the baseline low-level inflammation in aged mice mitigates the negative impact of androgens on WH. The far larger increase in CD301b+ cell activity in young mice exposed to testosterone as compared to aged mice may account for the more pronounced negative effects of T on WH in the young group. Future work will examine how testosterone’s immunosuppressive actions affect these hallmarks of senescent repair.