Skin senescence: mechanisms and impact on whole-body aging

The skin is the largest organ and has a key protective role. Similar to any other tissue, the skin is influenced not only by intrinsic/chronological aging, but also by extrinsic aging, triggered by environmental factors that contribute to accelerating the skin aging process. Aged skin shows structural, cellular, and molecular changes and accumulation of senescent cells. These senescent cells can induce or accelerate the age-related dysfunction of other nearby cells from the skin, or from different origins. However, the extent and underlying mechanisms remain unknown. In this opinion, we discuss the possible relevant role of skin senescence in the induction of aging phenotypes to other organs/tissues, contributing to whole-body aging. Moreover, we suggest that topical administration of senolytics/senotherapeutics could counteract the overall whole-body aging phenotype. With age, senescent cells accumulate in the skin and spread the aging phenotype to neighboring cells, resulting in decreased thickness, regenerative capacity, and a barrier effect in the skin.Aging and cellular senescence phenotypes in the skin were found to correlate with immunosenescence, longevity, or cardiovascular disease risk.Skin aging, induced by ultraviolet radiation, has an impact in the brain, by decreasing hippocampal neurogenesis and activating the central hypothalamic–pituitary–adrenal axis.Senolytics, such as dasatinib and fisetin, are drugs that selectively eliminate senescent cells and are already topically administered to the skin, showing potential antiaging effects.