The Role of Endoplasmic Reticulum Stress in Extrinsic Skin Aging and Protective Strategies of Natural Plant Products.

<h4>Background</h4>The complicated process of extrinsic skin aging is brought on by long-term exposure to ultraviolet (UV) radiation, air pollution, and other environmental stressors. Its primary manifestations include deep wrinkles, skin laxity, abnormal pigmentation, epidermal barrier dysfunction, chronic inflammation, and telangiectasia. According to recent research, endoplasmic reticulum stress (ERS) is an important stress mechanism involved in extrinsic skin aging. Through the production of reactive oxygen species (ROS), disruption of Ca2+ homeostasis, and defects in protein folding, extrinsic environmental stressors can activate ERS and cause the unfolded protein response (UPR).<h4>Summary</h4>ERS-induced UPR activation initially functions as a protective mechanism that restores endoplasmic reticulum (ER) homeostasis by enhancing protein-folding capacity, promoting ER-associated degradation (ERAD), and attenuating global protein translation. However, under persistent or severe ER stress, sustained UPR signaling may shift from a homeostatic response toward a detrimental response and contribute to the development of characteristic cutaneous phenotypes of extrinsic skin aging, including wrinkles, hyperpigmentation, epidermal barrier dysfunction, chronic inflammation, and telangiectasia, through increased oxidative stress, amplification of inflammatory responses, and induction of cellular senescence(definition) and apoptosis. An increasing amount of evidence suggests that natural plant products can prevent or alleviate extrinsic skin aging by regulating ERS and related processes, including apoptosis, autophagy(definition), and oxidative stress.<h4>Key messages</h4>This review summarizes the major molecular mechanisms of ERS in extrinsic skin aging and its associations with various aging phenotypes, outlining potential intervention strategies using natural plant products.