Sarandy Mariáurea Matias, Gonçalves Reggiani Vilela, Valacchi Giuseppe
Department of Animal Science, Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, NC 28081, USA.
Department of General Biology, Federal University of Viçosa, Viçosa 36570-900, MG, Brazil.
Biomedicines. 2024 Feb 1;12(2):348. doi: 10.3390/biomedicines12020348.
Our current understanding of skin cell senescence involves the role of environmental stressors (UV, O, cigarette smoke, particulate matter, etc.), lifestyle (diet, exercise, etc.) as well as genetic factors (metabolic changes, hormonal, etc.). The common mechanism of action of these stressors is the disturbance of cellular redox balance characterized by increased free radicals and reactive oxygen species (ROS), and when these overload the intrinsic antioxidant defense system, it can lead to an oxidative stress cellular condition. The main redox mechanisms that activate cellular senescence in the skin involve (1) the oxidative damage of telomeres causing their shortening; (2) the oxidation of proteomes and DNA damage; (3) an a in lysosomal mass through the increased activity of resident enzymes such as senescence-associated β-galactosidase (SA-β-gal) as well as other proteins that are products of lysosomal activity; (4) and the increased expression of SASP, in particular pro-inflammatory cytokines transcriptionally regulated by NF-κB. However, the main targets of ROS on the skin are the proteome (oxi-proteome), followed by telomeres, nucleic acids (DNAs), lipids, proteins, and cytoplasmic organelles. As a result, cell cycle arrest pathways, lipid peroxidation, increased lysosomal content and dysfunctional mitochondria, and SASP synthesis occur. Furthermore, oxidative stress in skin cells increases the activity of p16 and p53 as inhibitors of Rb and CDks, which are important for maintaining the cell cycle. p53 also promotes the inactivation of mTOR-mediated autophagic and apoptotic pathways, leading to senescence. However, these markers alone cannot establish the state of cellular senescence, and multiple analyses are encouraged for confirmation. An updated and more comprehensive approach to investigating skin senescence should include further assays of ox-inflammatory molecular pathways that can consolidate the understanding of cutaneous redox senescence.
我们目前对皮肤细胞衰老的理解涉及环境应激源（紫外线、臭氧、香烟烟雾、颗粒物等）、生活方式（饮食、运动等）以及遗传因素（代谢变化、激素等）的作用。这些应激源的共同作用机制是细胞氧化还原平衡的紊乱，其特征是自由基和活性氧（ROS）增加，当这些物质超过内在抗氧化防御系统的负荷时，会导致细胞处于氧化应激状态。皮肤中激活细胞衰老的主要氧化还原机制包括：（1）端粒的氧化损伤导致其缩短；（2）蛋白质组的氧化和DNA损伤；（3）通过衰老相关β-半乳糖苷酶（SA-β-gal）等驻留酶以及溶酶体活性产物等其他蛋白质活性的增加，导致溶酶体质量增加；（4）衰老相关分泌表型（SASP）的表达增加，特别是由核因子κB（NF-κB）转录调控的促炎细胞因子。然而，ROS在皮肤上的主要靶点是蛋白质组（氧化蛋白质组），其次是端粒、核酸（DNA）、脂质、蛋白质和细胞质细胞器。结果，出现细胞周期停滞途径、脂质过氧化、溶酶体含量增加和线粒体功能障碍以及SASP合成。此外，皮肤细胞中的氧化应激会增加作为Rb和周期蛋白依赖性激酶（CDks）抑制剂的p16和p53的活性，这对维持细胞周期很重要。p53还会促进雷帕霉素靶蛋白（mTOR）介导的自噬和凋亡途径的失活，从而导致细胞衰老。然而，仅凭这些标志物无法确定细胞衰老的状态，建议进行多项分析以进行确认。一种更新的、更全面的研究皮肤衰老的方法应包括对氧化炎症分子途径的进一步检测，这有助于巩固对皮肤氧化还原衰老的理解。
