赤松 浩彦

The skin is a tissue highly susceptible to damage from various stressors, including reactive oxygen species, UV radiation and chemical exposure. While damaged cells are often repaired, some sustain irreversible damage and become senescent. Although the body possesses mechanisms to remove these senescent cells, they accumulate with age for reasons that remain unclear. The close relationship between chronic inflammation and cellular senescence has recently become a major focus of research. Here, we sought to analyse the mechanisms driving age-related chronic inflammation and its impact on the accumulation of senescent cells. Our analysis of the cytokine IL-17A, a key factor in chronic inflammation, revealed that its levels increase in the skin with age. We also discovered that regulatory T cells (Treg cells), which typically act to suppress IL-17A, begin to secrete it as they age. Moreover, we found that IL-17A enhances the resistance of senescent cells to apoptosis. These results propose a model in which the age-related rise in the inflammatory factor IL-17A fosters an environment where senescent cells resist clearance, thereby promoting their accumulation.

The skin, the body's largest organ, covers the entire body and consists of three layers: the epidermis, dermis, and subcutaneous tissue. Its structure and properties vary by body region. Although homeobox (HOX) genes are implicated in mechanisms contributing to regional skin property differences, their influence is not completely understood. In this study, we focused on the relationships between HOX gene expression to regional differences in dermal structure and skin elasticity. Our results revealed significantly higher HOXA cluster expression in skin tissues and cells derived from the body in comparison to those derived from the face. Among HOXA genes highly expressed in the body, HOXA9 was found to regulate dermal fibroblast proliferation and extracellular matrix (ECM)-related gene expression, both associated with skin elasticity. Furthermore, HOXA9 was shown to affect cell proliferation and ECM-related gene expression through IGF-1 signaling. Collectively, our findings suggest that HOXA genes are expressed differently in different body regions, variably affecting dermal structure and cellular functions, thus contributing to regional variation in skin.