Idiopathic guttate hypomelanosis (IGH) as one of skin manifestations in aging is a common pigmentary skin disorder characterized by multiple hypomelanotic macules. Although IGH is very common, even universal in the elderly, exact etiology of IGH is still unclear. Clinical associations such as sun exposure, skin aging, and repeated microtrauma suggest the involvement of cellular senescence in IGH. Moreover, recent studies revealed that cellular senescence is not only the consequence of aging process but also a crucial cause of aging and aging-related diseases via secretion of various mediators, creating the senescence-associated secretory phenotype (SASP). Therefore, we hypothesized that cellular aging as well as SASP, which are altered in lesional skin of IGH, are associated with development of IGH. To evaluate the role of SASP in IGH, the number of senescent cells and SASP were histologically compared between lesional and perilesional skins in 31 patients with IGH. As expected, both the extent of pigmentation and melanocyte number were significantly decreased in lesional skins compared to non-lesional skins. Interestingly, the number of p16-expressing cells and SASP-associated molecules including MMP1 were significantly increased in lesional skins. To evaluate the functional consequences of the SASP in decreased number of melanocytes and hypopigmentation, the effect of culture medium derived from ultraviolet light-induced senescent fibroblasts (Senescent FB medium) on melanocytes was examined. Senescent FB medium induced senescence of melanocyte and decreased viability and proliferation of melanocyte compared to control medium. Collectively, our findings suggest that increased number of senescent cells and their SASP may be implicated in the pathogenesis of IGH.

The Senescence-Associated Secretory Phenotype May Play a Role in Idiopathic Guttate Hypomelanosis