Klotho Mice: A Novel Wound Model of Aged Skin

BACKGROUND As the elderly population continues to expand, it becomes increasingly important to develop treatments to improve wound healing in the elderly. One problem limiting the research is the lack of appropriate animal models for wound healing in elderly patients. We hypothesized that the Klotho mouse of premature aging is a suitable animal model to shed light on many of the biological processes involved in aging skin. METHODS Klotho mice (kl/kl), Klotho-heterozygous mice (kl/+), and wild-type mice (+/+) were wounded, and the area of the wound was measured every 3 days until the wound was healed. To compare the klotho phenotype with wild-type mice, wounds were also harvested at 4 and 7 days after wounding. For histological examination, paraffin-embedded sections were stained with hematoxylin and eosin and Masson trichrome. Collagen expression in the wound was also studied by analyzing messenger RNA using real-time polymerase chain reaction. RESULTS Klotho mice showed a significantly slower rate of wound closure compared with Klotho-heterozygous mice and wild-type mice. Histology showed substantial less healing and collagen deposition in the wounds of the Klotho mice. The expression of collagen messenger RNA in Klotho mice was also less than that in heterozygous and wild-type mice. The Klotho mice exhibited significant phenotypic similarities with aged skin, such as atrophy and delayed wound healing. CONCLUSION These preliminary data suggest that the Klotho mouse may be a model to further investigate wound healing in the elderly.