Cellular senescence in skin-related research: Targeted signaling pathways and naturally occurring therapeutic agents

Abstract

Despite the growing interest by researchers into cellular senescence, a hallmark of cellular aging, its role in human skin remains equivocal. The skin is the largest and most accessible human organ, reacting to the external and internal environment. Hence, it is an organ of choice to investigate cellular senescence and to target root-cause aging processes using senolytic and senomorphic agents, including naturally occurring plant-based derivatives. This review presents different aspects of skin cellular senescence, from physiology to pathology and signaling pathways. Cellular senescence can have both beneficial and detrimental effects on the skin, indicating that both prosenescent and antisenescent therapies may be desirable, based on the context. Knowledge of molecular mechanisms involved in skin cellular senescence may provide meaningful insights for developing effective therapeutics for senescence-related skin disorders, such as wound healing and cosmetic skin aging changes.

Keywords: cellular senescence; senescence-related skin disorders; senolytic agents; senomorphic agents; skin aging.

FIGURE 1

Structural differences between young (left panel) and aged, elderly skin (middle panel). Senescent cells (red) accumulate in aged skin. Right panel: Senescent cells are characterized by upregulation of p21 and p16, secretion of the senescence‐associated secretory phenotype (SASP), increased β‐galactosidase activity, translocation of HMGB1, reduced laminin B1 expression, accumulation of ROS, aberrant of the MAPK‐FOXO3, and modulation of the Nrf2, mTOR and Notch pathways, and DNA damage. DEJ, dermo‐epidermal junction; SC, stratum corneum.