![]() Among these factors, UV irradiation is considered to be most deleterious in inducing cellular senescence and aging in the skin. ROS can be engendered by a variety of sources, such as UV light, environment pollution, mitochondria respiration. Accumulation of molecular damage due to reactive oxygen species (ROS) generation has long been thought to drive skin aging, indicating oxidative stress as a causative factor of skin senescence. Cellular senescence induces aberrant collagen homeostasis and causes gradual loss of epidermal stem cell function, which will eventually disrupt the structural integrity and the function of skin, resulting in skin aging. However, senescence also contributes to age-related pathologies in various tissues, especially in the skin. Senescence is an important mechanism that protects cells from oncogenic stresses. Keywords: autophagy, caffeine, cellular senescence, skin aging, UV radiation Introduction These discoveries implicate the potential of caffeine in the protection of skin disease. Our study not only demonstrated the beneficial effect of caffeine using both in vitro and in vivo models, but also systematically investigated the underlying molecular mechanisms. On the other hand, co-administration with autophagy inhibitors attenuated the protective effect of caffeine on UV-induced skin damage in mice.Ĭonclusion: The results reveal that caffeine protects skin from oxidative stress-induced senescence through activating the A2AR/SIRT3/AMPK-mediated autophagy. Oral administration of caffeine increased the protein level of SIRT3, induced autophagy, and reduced senescence and tissue damage in UV-irradiated mouse skin. Using a combination of RNAi and chemical treatment, we demonstrate that caffeine activates autophagy through a series of sequential events, starting from the inhibition of its primary cellular target adenosine A2a receptor (A2AR) to an increase in the protein level of Sirtuin 3 (SIRT3) and to the activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Mechanistically, caffeine facilitated the elimination of ROS by activating autophagy. Remarkably, low dose of caffeine (<10 μM) suppressed cellular senescence and skin damage induced by AAPH or UV. Similarly, UV irradiation induced senescence in mouse skin tissues. Results: We report that AAPH induced senescence in both transformed skin cells and in NHEKs. Reactive oxygen species (ROS) detection by commercial kits, gene knockdown by RNA interference (RNAi) and receptor activation/inactivation by agonist/antagonist treatment were applied in mechanistic experiments. Activation of autophagy was confirmed by western blotting, immunofluorescence, and transmission electron microscopy. Cellular senescence was determined by SA β-galactosidase staining, immunofluorescence and western blotting. Ultraviolet (UV) irradiation was established as the in vivo oxidative stress model in mouse skin tissues. Methods: A free radical inducer 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was used to induce oxidative stress and cellular senescence in both transformed skin cells and in normal human epidermal keratinocytes (NHEKs). This study aims to investigate whether caffeine, a well-known purine alkaloid, is able to prevent skin from oxidative stress-induced senescence, and to explore the underlying molecular mechanisms. ![]() Therefore, strategies that can ameliorate oxidative stress-induced senescence are expected to protect skin from damage, holding the promise of treating skin diseases in the clinic. Skin cells are vulnerable to oxidative stress-induced senescence, which may lead to abnormal aging or aging-related disorders. Select the file that you have just downloaded and select import option Reference Manager (RIS). Caffeine Protects Skin from Oxidative Stress-Induced Senescence through the Activation of Autophagy. ![]() Li YF, Ouyang SH, Tu LF, Wang X, Yuan WL, Wang GE, Wu YP, Duan WJ, Yu HM, Fang ZZ, Kurihara H, Zhang Y, He RR. ![]()
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