An effective method to protect the skin from natural aging is unknown. Therefore, in this study, we examined the ameliorative effects of tranexamic acid on natural skin aging. In addition, we examined the sex difference in the effect exhibited by tranexamic acid. We bred hairless mice without ultraviolet ray irradiation and physical stress for 2 years. During the study period, mice were orally administered tranexamic acid (12 mg/kg/day) three times per week. Development of signs of skin aging was found to be ameliorated by tranexamic acid. Furthermore, synthetic inhibition of plasmin was observed following tranexamic acid treatment. The synthetic reinforcement of hyaluronic acid by an increase in the number of epidermal cells and the degradative inhibition of extracellular matrix (ECM) by matrix metalloproteinase (MMP) suppression were observed. These results indicate that natural skin aging was ameliorated by tranexamic acid via the regulation of the plasmin/TGF-β/epidermal cells/hyaluronic acid and plasmin/MMPs/ECM signal transmission pathways. Taken together, sex difference was observed for the ameliorative effect of tranexamic acid on skin aging, with a stronger effect observed in females than in males. More importantly, we found that the synthesis of hyaluronic acid was stronger in female mice than in male mice.
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