Cell Autonomous and Non-Autonomous Effects of Senescent Cells in the Skin

Abstract

Human and mouse skin accumulate senescent cells in both the epidermis and dermis during aging. When chronically present, senescent cells are thought to enhance the age-dependent deterioration of the skin during extrinsic and intrinsic aging. However, when transiently present, senescent cells promote optimal wound healing. Here, we review recent studies on how senescent cells and the senescence-associated secretory phenotype contribute to different physiological and pathophysiological conditions in the skin with a focus on some of the cell autonomous and non-autonomous functions of senescent cells in the context of skin aging and wound healing.

Figure 1. Senescent cells act in the skin via both cell autonomous and non-autonomous mechanisms

The transient induction of cellular senescence during wound healing promotes granulation tissue formation and tissue remodeling, while it prevents the hyperproliferation of potentially premalignant or malignant lesions. In contrast, the accumulation of senescent cells with age causes poor tissue regeneration and loss of homeostasis in the skin. The chronic presence of senescent cells further creates a tissue environment with chronic inflammation promotes collagen degradation, both of which can lead to aging phenotypes in the skin.