端粒与皮肤老化

人类皮肤老化分为内源性和外源性两种,紫外线辐射是外源性老化的最主要因素,所以又称为光老化。细胞染色体末端的特殊结构———端粒,在皮肤老化过程中扮演了非常重要的角色。细胞多次分裂造成的端粒进行性缩短很大程度上控制了内源性老化。暴露于日光的皮肤,紫外线辐射也可损伤DNA,加速端粒缩短。无论是内源性老化还是光老化,在端粒环破裂后均通过p 53肿瘤抑制蛋白途径启动了DNA损伤信号传递。这一共同的路径解释了自然老化和光老化皮肤的广泛相似性,预示着对一种老化进程采取有效的预防和治疗措施可能对其他进程产生良性影响。     

紫外线照射对成纤维细胞染色体端粒DNA复制的影响

目的:旨在DNA水平探讨紫外线启动人皮肤光老化的机制,以加深对光老化的理解,并为减缓光老化进程提供新靶点.方法:紫外线照射原代人成纤维细胞,用比色法测定成纤维细胞的增殖活性;用1 000 mJ/cm2紫外线照射细胞,采用实时定量PCR方法测定照射与未照射细胞不同代数的端粒长度;不同剂量紫外线照射同代细胞,并测定端粒长度.结果:紫外线照射与未照射细胞的端粒长度均有随着细胞的复制传代而逐渐缩短趋势;在不同剂量紫外线照射的同一代细胞之间,紫外线剂量越高,端粒长度则越短,高剂量组与未照射组相比有统计学差异(P<0.05).结论:单次大剂量紫外线照射可以使端粒长度变短.急性光损伤可能启动光老化的早期进程.     

外用含维生素C、阿魏酸和根皮素的抗氧化制剂对紫外线诱导的皮肤光损伤的保护功效

UV可诱发氧化应激反应.由皮肤暴露于UV后所导致的细胞水平上的活性氧簇(ROS)增加,将对表皮细胞和真皮细胞中的脂类、蛋白和核酸造成损伤,从而参与晒伤反应、皮肤光老化及光致癌效应.该文通过检测皮肤光损伤相关生物标记研究了含维生素C、阿魏酸(ferulic anid)和根皮素(phloretin)外用制剂对健康志愿者UV所致皮肤光损伤的保护效应.     

外用含维生素C、阿魏酸和根皮素的抗氧化制剂对紫外线诱导的皮肤光损伤的保护功效

UV可诱发氧化应激反应.由皮肤暴露于UV后所导致的细胞水平上的活性氧簇(ROS)增加,将对表皮细胞和真皮细胞中的脂类、蛋白和核酸造成损伤,从而参与晒伤反应、皮肤光老化及光致癌效应.该文通过检测皮肤光损伤相关生物标记研究了含维生素C、阿魏酸(ferulic anid)和根皮素(phloretin)外用制剂对健康志愿者UV所致皮肤光损伤的保护效应.     

外用含维生素C、阿魏酸和根皮素的抗氧化制剂对紫外线诱导的皮肤光损伤的保护功效

UV可诱发氧化应激反应.由皮肤暴露于UV后所导致的细胞水平上的活性氧簇(ROS)增加,将对表皮细胞和真皮细胞中的脂类、蛋白和核酸造成损伤,从而参与晒伤反应、皮肤光老化及光致癌效应.该文通过检测皮肤光损伤相关生物标记研究了含维生素C、阿魏酸(ferulic anid)和根皮素(phloretin)外用制剂对健康志愿者UV所致皮肤光损伤的保护效应.     

Nrf2基因在紫外线氧化应激与光老化中的作用研究进展

皮肤是直接暴露于日光紫外线照射的人类器官,紫外线的照射可导致皮肤的多种损伤,如光老化以及各种皮肤肿瘤。重复的细胞光损伤是导致皮肤光老化的基础。研究发现,紫外线辐射于人体皮肤发生氧化应激反应,产生的活性氧簇(reactive oxygen species,ROS)是导致细胞光损伤的主要原因。Nrf 2在很多与氧化应激反应相关的病变中均发挥重要的防御保护作用,Nrf2缺失或激活障碍会增加细胞对紫外线辐射的敏感性,而加重细胞的光损伤以及光老化。该文综述了Nrf2基因在光损伤以及光老化中的重要保护作用。     

基质金属蛋白酶与基质金属蛋白酶抑制剂在光老化中作用的研究进展

紫外线照射会给人体的皮肤造成有害影响,其中,光老化是目前公认的长期暴露于紫外线照射所造成的主要危害之一.紫外线照射导致了基质金属蛋白酶家族的表达增加,其可降解真皮中的胶原及其他细胞外基质蛋白.大量的皮肤正常结缔组织结构的破坏损害了皮肤的功能并引起皮肤的老化.基质金属蛋白酶抑制剂是基质金属蛋白酶家族特异性的内源性抑制剂,并参与调控其在机体组织中的活性变化.二者之间的平衡在皮肤光老化的发生与发展中占有举足轻重的地位.     

皮肤光老化组织学改变研究进展

皮肤光老化是不断累积的日光照射所致的一个连续性过程,是指长期的日光照射(主要是紫外线)导致皮肤衰老.在组织学方面,表皮变化主要是角质形成细胞、黑素细胞、朗格汉斯细胞,真皮变化主要是弹力纤维变性和胶原减少.其机制主要涉及免疫系统、细胞因子改变、基质金属蛋白酶生成增加、活性氧簇增加及DNA损伤等.概述并探讨皮肤光老化组织学变化及其相应的发生机制.     

皮肤光老化的治疗现状

皮肤老化通常分为内源性老化和外源性老化.而外源性老化主要由环境因素如紫外线辐射、吸烟、风吹、日晒及接触有害化学物质等引起.由于日光中紫外线辐射是环境因素中导致皮肤老化的最主要因素,所以皮肤外源性老化又称为皮肤光老化.     

皮肤光老化发生机制的研究进展

皮肤光老化是由于紫外线的长期慢性辐射损害而造成的皮肤损伤,在临床表现、组织病理学等方面与自然老化有着不同的表现.近年国内外关于光老化发生机制方面的研究有了很大的进展,研究已经证实,激活蛋白-1和核因子-кB活化导致基质金属蛋白酶的合成、线粒体损伤、蛋白质氧化和端粒在光老化发生中的作用.理解并认识这些发生机制有助于在防治慢性紫外线辐射造成的皮肤损伤方面提出新的预防和治疗策略.     

Genetic basis for skin youthfulness

Aging skin is a consequence of both intrinsic factors, including genetics, and extrinsic factors, including environmental exposures such as ultraviolet (UV) radiation and smoking. This contribution focuses on intrinsic factors that promote aging skin. Specifically, in this contribution we review the literature describing how single nucleotide polymorphisms, epigenetic changes, variable gene expression, microRNA, and mitochondrial depletion relate to skin aging. Investigations studying intrinsic factors associated with skin aging are important as they promote a better understanding of the underlying pathophysiology of aging skin. This contribution also describes potential avenues for future genetic research in skin aging. Molecular mechanisms that may be therapeutically intervened upon are of particular interest given the cultural value placed on youthful appearing skin. Future research efforts will hopefully reveal a means upon which to intercede on the skin aging process.     

Skin aging

There are two main processes that induce skin aging: intrinsic and extrinsic. A stochastic process that implies random cell damage as a result of mutations during metabolic processes due to the production of free radicals is also implicated. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsic aging reflects the genetic background and depends on time. Various expressions of intrinsic aging include smooth, thinning skin with exaggerated expression lines. Extrinsically aged skin is characterized by photo damage as wrinkles, pigmented lesions, patchy hypopigmentations, and actinic keratoses. Timely protection including physical and chemical sunscreens, as well as avoiding exposure to intense UV irradiation, is most important. A network of antioxidants such as vitamins E and C, coenzyme Q10, alpha-lipoic acid, glutathione, and others can reduce signs of aging. Further anti-aging products are three generations of retinoids, among which the first generation is broadly accepted. A diet with lot of fruits and vegetables containing antioxidants is recommended as well as exercise two or three times a week.     

Hautalterung

Like the entire human organism, the skin is subject to an intrinsic unpreventable aging process. But exogenous factors also influence skin aging. Ultraviolet radiation in particular results in premature skin aging, also referred to as extrinsic skin aging or photo aging, causing in large part aging-associated changes in sun-exposed areas. Intrinsic and extrinsic aging share several molecular similarities despite morphological and pathophysiological differences. The formation of reactive oxygen species and the induction of metalloproteinases reflect central aspects of skin aging. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for further degradation of extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin aging and the detection of its mechanisms has given rise to development of various therapeutic and preventive strategies.     

过氧化物酶体增殖激活物受体γ在皮肤自然衰老过程中的表达及意义

目的研究过氧化物酶体增殖激活物受体γ（PPARγ）在皮肤自然衰老过程中的表达及其意义。方法采用免疫组化方法（SP法）检测PPARγ的蛋白表达水平，RT—PCR方法检测PPARγ的mRNA表达水平。结果免疫组化研究结果表明中老年组PPARγ蛋白的表达强度显著高于青少年组（x^2=15．48，P=0．001）；RT—PCR检测结果表明中老年组PPARγmRNA的平均表达水平为0．697±0．204，青少年组为0．337±0．124，中老年组亦显著高于青少年组（t=8．25，P〈0．001）。结论随着年龄的增加，皮肤PPARγ的表达增高，在皮肤自然老化过程中可能起重要作用，PPARγ有可能成为研制延缓皮肤自然衰老药物的新靶点。     

Proposed mechanisms of action for retinoid derivatives in the treatment of skin aging

Skin aging (intrinsic aging) and photoaging (extrinsic aging) involve a similar process that leads to the typical creased appearance of the skin, with the progressive loss of its physical and biologic properties. Photoaging is a premature skin aging caused by long-term exposure to the ultraviolet B radiations of the sun, and is more frequently associated to skin cancer than intrinsic aging. Retinoids are natural and synthetic vitamin A derivatives. They are lipophilic molecules and penetrate the epidermis easily. Their biologically active forms can modulate gene expression by binding to nuclear receptors and then to specific DNA sequences. Because of their ability to modulate genes involved in cellular differentiation and proliferation, they appear as good candidates to treat and prevent photoaging. Hyaluronate and collagen, two major constituents of the dermis, are progressively decreased and altered during aging. Various retinoids were shown to increase their synthesis and concentration in the skin and reduce their rate of degradation. Furthermore, retinoids share a common chemical structure containing several conjugated double bonds that enable them to trap free radicals and absorb UV radiations from the sun, thereby protecting cellular targets such as DNA, lipid membranes, or proteins by preventing direct photochemical damage or UV-induced oxidative stress. Therefore, retinoids may be beneficial in treating skin aging and photoaging because of their biologic, chemical, and physical properties, which act at several levels.     

Angiogenesis in skin aging and photoaging

Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process.     

Physiological consequences of human skin aging

The expression and treatment of cutaneous disease in the elderly differ from those applicable to younger adults. Anatomical changes in aging skin result in altered physiological behavior and susceptibility to disease. Decreased epidermal renewal and tissue repair accompany the aging process. The rate of hair and nail growth declines, as well as the quantity of eccrine, apocrine, and sebum secretion. There are alterations in immune surveillance and antigen presentation with aging. The cutaneous vascular supply is decreased, leading to decreases in inflammatory response, absorption, and cutaneous clearance. Impaired thermal regulation, tactile sensitivity, and pain perception occur as one ages. We summarize the major changes that occur during the intrinsic aging process of the skin to facilitate the recognition and treatment of skin disease in the older patient.     

Facial changes in the mature patient

During the aging process, the appearance of the human face changes significantly due to fundamental alterations in the bones, soft tissues, and skin. Both endogenous and environmental factors are involved in age-related transformations of the face; however, facial skin is particularly influenced by environmental factors, and the risk of overexposure and consequent premature facial aging. This review summarizes the current state of knowledge of the most common facial skin changes in the mature patient, including pathogenesis of both intrinsic and extrinsic skin aging, as well as clinical and histologic features of skin aging. Because the majority of facial skin changes in the elderly develop as the consequence of ultraviolet radiation, these can be prevented by adequate photoprotection.     

Relative contribution of intrinsic vs extrinsic factors to skin aging as determined by a validated skin age score

OBJECTIVE: To assess the relative contribution of intrinsic aging vs lifestyle factors to facial skin age. DESIGN: Prospective analysis of a cohort. SETTING: Skin research institute. STUDY SUBJECTS: A cohort of 361 white women (age range, 18-80 years) with apparently healthy skin. MEASUREMENTS: Visual and tactile assessment of facial skin features. RESULTS: Twenty-four skin characteristics were used to build a skin age score (SAS). The relationship between the SAS and chronological age followed a linear model with 2 plateaus--1 before age 30 years and 1 after age 71 years. An analysis was performed to determine whether certain lifestyle habits known to have effects on skin aging were related to the discrepancies between chronological age and the SAS. Significant effects were identified for phototype, body mass index, menopausal status, degree of lifetime sun exposure, and number of years of cigarette smoking. However, these factors accounted for only 10% of the discrepancies. Moreover, most skin characteristics used reflected changes understood to represent intrinsic aging rather than photodamage or other extrinsic factors. CONCLUSIONS: An SAS can be generated from multiple discrete signs evaluated on facial skin and is an informative tool for quantifying skin aging. The SAS is influenced by factors already recognized to affect the aging phenotypes; however, factors related to the rate of intrinsic aging, presumably genetic in character, seem to play a larger role than previously suspected.