皮肤受内源性和外源性因素的影响，这些因素是衰老的直观后果表达。衰老不仅影响皮肤的美观，还导致皮肤功能的下降，引发许多皮肤疾病甚至皮肤癌。抗衰老配方(AAF)具有抗氧化、调节肠道菌群代谢、抗衰老和改善记忆等多种生物学效应。然而，尚不清楚它是否能抗衰老皮肤及其抗衰老机制。本研究旨在调查AAF是否能预防氧化应激诱导的皮肤衰老，并探索其潜在的分子机制。我们基于紫外线(UV)照射建立了小鼠皮肤氧化应激衰老模型，并测量了皮肤水分含量、黑色素生成、皱纹产生、病理变化和衰老标志蛋白等参数，以阐明AAF是否对皮肤具有抗衰老作用。随后，利用转录组测序(RNA-Seq)鉴定靶基因。我们建立了体外细胞衰老模型，通过检测衰老相关标志物评估AAF对细胞氧化应激衰老的作用，同时通过靶基因的沉默或过表达阐明AAF在延迟皮肤衰老方面的特定作用机制。体内实验证明，AAF显著增加了皮肤水分含量，减轻了皮肤敏感度和黑色素含量，减缓了皱纹产生，改善了UV诱导的表皮增厚，增加了胶原纤维含量，改善了弹性纤维形态，并减少了皮肤组织中衰老蛋白P21和P16的表达。RNA-Seq结果确定了趋化因子受体2 (CXCR2) 作为延缓皮肤衰老的潜在靶点之一。体外实验显示，AAF显著改善了衰老表型，而沉默或过表达实验证实了CXCR2在皮肤衰老过程中的重要作用。机制研究表明，AAF通过降低CXCR2的表达，抑制了P38/P53通路的活化，从而改善了衰老表型，减少了氧化损伤，最终延缓了细胞衰老。结果表明，AAF通过调节关键靶点CXCR2的表达，降低P38蛋白的磷酸化，抑制P53通路的活化，保护皮肤免受氧化应激诱导的衰老。这些发现揭示了AAF在保护皮肤衰老疾病方面的潜力。 Copyright © 2023. Published by Elsevier B.V.

The skin is affected by endogenous and exogenous factors, which are the intuitive consequence expression of aging. Aging not only affects the aesthetics of the skin but also causes the decline of skin functions, leading to many skin diseases and even skin cancer. Anti-aging formula (AAF) has various biological effects such as antioxidants, regulation of intestinal flora metabolism, anti-aging, and memory improvement. However, it is not clarified whether it could be anti-aging of the skin and the anti-aging mechanism.This study aimed to investigate whether AAF could prevent skin from oxidative stress-induced senescence and explore the underlying molecular mechanisms.A mouse skin oxidative stress aging model was established based on ultraviolet (UV) irradiation, and parameters such as skin water content, melanogenesis, wrinkle production, pathological changes, and aging marker proteins were measured to elucidate whether AAF has an anti-aging effect on the skin. Subsequently, transcriptome sequencing (RNA-Seq) was used to identify target genes. An in vitro cellular senescence model was established to assess the role of AAF against cellular oxidative stress senescence by detecting senescence-related markers, while the specific mechanism of action of AAF in delaying skin senescence was elucidated by silencing or overexpression of targets.In vivo experiments demonstrated that AAF significantly increased skin water content, reduced skin sensitivity and melanin content, slowed wrinkles, improved UV-induced epidermal thickening, increased collagen fiber content, improved elastic fiber morphology, and reduced the expression of senescence proteins P21 and P16 in skin tissues. The RNA-Seq results identified chemokine receptor 2 (CXCR2) as one of the potential targets for delaying skin senescence. In vitro experiments showed that AAF markedly improved the aging phenotype, and knockdown or overexpression experiments verified the essential role of CXCR2 in the skin senescence process. Mechanistic studies suggested that AAF inhibited the P38/P53 pathway by reducing CXCR2 expression, which improved the aging phenotype, reduced oxidative damage, and ultimately delayed cellular senescence.The results reveal that AAF protects skin from oxidative stress-induced senescence by regulating the expression of critical target CXCR2, reducing P38 protein phosphorylation, and inhibiting P53 pathway activation. These discoveries implicate the potential of AAF in the protection of skin aging disease.Copyright © 2023. Published by Elsevier B.V.