Purpose: Endothelial cells maintain the homeostasis of blood, which consists of plasma and cellular components, and regulate the interaction between blood and the surrounding tissues They also have essential roles in vascular permeability, the circulation, coagulation, inflammation, wound healing, and tissue growth The senescence of endothelial cells is closely related to the aging of the adjacent tissues and to age-related vascular disease Recently, the expression of moesin was found to be decreased in elderly human dermal microvascular endothelial cells (HDMECs), and an association between moesin and senescence has been suggested This study examined the functional role of moesin in cellular senescence Materials and Methods: To study the effects of decreased moesin expression on cellular senescence and metabolism. HDMECs were transfected with short hairpin-RNA (shRNA) lentivirus to silence moesin gene expression In addition, specimens from young and old human skin were stained with antimoesin and anti-p16 antibodies as an in vivo study Results: Using shRNA-lentivirus, moesin knock-down HDMECs developed characteristics associated with ailing and expressed senescence associated-beta-galactosidase during early passages They also showed increased p16 expression, decreased metabolic activity, and cell growth retardation Human skin tissue from elderly persons showed decreased moesin expression and increased p16 expression Conclusion: These findings suggest that there is a functional association between moesin expression and cellular senescence. Further study of the functional mechanism of moesin in the cytoskeleton and cellular senescence is needed In addition, this study provides a useful model for developing anti-aging treatments