Senescence is a term used for biologic aging. Leonard Hayflick highlighted senescence in the 1960s, when he showed that fibroblasts in culture can replicate 50 times before entering cellular senescence, a new state of existence of the cell without replication. These senescent cells (SCs) are usually larger than non-senescent cells, and tend to have a distinct secretome termed Senescence Associated Secretory Phenotype (SASP). SCs acquire new markers and can be identified. Cellular senescence is a normal and necessary phenomenon. However, a dysregulation of senescence can cause disease and dysfunction. SASP induced secondary to ultraviolet radiation, oxidative stress, radiation exposure, chronic inflammation, carcinogenesis, to name a few, can induce a pro-inflammatory SASP that causes local and distant disease. In fact, transplanting relatively small numbers of senescent fibroblasts into young mice from syngeneic older mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues. Transplanting even fewer senescent cells had the same effect in older recipients and was accompanied by reduced survival, indicating the potency of senescent cells in shortening health- and lifespan. Cellular senescence has been studied in many animal models and cell types. It is especially well studied in skin using keratinocytes, melanocytes, fibroblasts, and adipocytes. Numerous studies have shown that using senotherapeutics, senescence can be reduced and diseases caused by senescence minimized. Senotherapeutics are classified as senolytics which kill SCs selectively; senomorphics which modulate functions and morphology of SCs to those of younger cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. We will review the potential use of senotherapeutics in dermatology.
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