抗氧化剂对防晒剂的补助光防护功效

紫外线(UV)照射是导致皮肤氧化应激的主要原因之一.慢性UV照射能增加人皮肤细胞中的活性氧簇(ROS),损伤表皮和真皮细胞内的脂质、蛋白质和核酸,并导致皮肤的光老化. 长波紫外线(UVA)约占到达地表UV的95％,已证实与ROS的产生和皮肤光老化关系最为密切.防晒剂能够抵御UV照射对皮肤造成的伤害,包括减少日光对皮肤所致的短期急性和长期慢性损伤.但通常由于防晒剂的使用量不足和涂抹不均匀,难以达到100％的理想防护功效.     

光动力治疗光老化及对皮肤屏障的影响

日光累积照射可导致皮肤光老化(photoaging),不仅加速皮肤外观的衰老,也增加皮肤癌前病变和皮肤肿瘤的发生风险,亦影响皮肤屏障功能。皮肤屏障(skin barrier)作为机体的最外层防线,保护皮肤免受外界不良因素损伤,亦防止机体水分及营养物质等流失,其功能的稳定性与皮肤光老化密切相关。近年来的临床研究证实,光动力疗法(photodynamic therapy,PDT)对皮肤光老化的疗效确切,并且可以同时改善皮肤屏障功能。光动力治疗光老化的机制主要体现在对真皮胶原的重塑,改善皮肤屏障的具体机制尚不明确,可能与光动力对角质形成细胞的作用有关。     

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。     

反复紫外线损伤后人体皮肤组织蛋白酶K活性变化

目的:在人体光老化皮肤中检测组织蛋白酶K的活性变化,为探讨皮肤光老化机制提供实验依据.方法:日光模拟紫外线反复照射[剂量为最小红斑量(MED),5 d/周,共6周]8例成人臀部皮肤,诱导光老化后,检测照射部位局部组织蛋白酶K活性变化.结果:和对照组皮肤相比,紫外线照射诱导后的皮肤组织蛋白酶K活性明显下降(P ＜ 0.001).结论:组织蛋白酶K在紫外线反复照射诱导的皮肤中活性明显降低,提示其与皮肤光老化密切相关.推测紫外线可能通过降低皮肤组织蛋白酶K活性使弹性纤维降解减少,从而导致其在真皮层堆积.     

5-氨基酮戊酸联合强脉冲光治疗皮肤光老化

皮肤光老化主要由日光中的紫外线长期累积性照射引起,而光老化中的皱纹和皮肤粗糙则是困扰患者的常见问题,迫使患者急切需要去改善老化的皮肤.近年来局部使用5-氨基酮戊酸(5-ALA)联合强脉冲光治疗皮肤光老化的应用逐渐引起重视,且其疗效已得到证实,其操作简单、疗效确切、无明显不良反应,治疗前后皮肤组织病理表现有所改变,但治疗机制还不十分明确.该文主要综述局部使用5-ALA联合强脉冲光治疗皮肤光老化的研究进展.     

Split-face模式评价强脉冲光治疗面部光老化的疗效

皮肤光老化为日光曝露部位皮肤出现的特有的外观和组织学变化[1].强脉冲光(intense pulsed light,IPL)技术作为新一代非剥脱性皮肤美容术,在治疗光老化方面具有很大优势.     

Split-face模式评价强脉冲光治疗面部光老化的疗效

皮肤光老化为日光曝露部位皮肤出现的特有的外观和组织学变化[1].强脉冲光(intense pulsed light,IPL)技术作为新一代非剥脱性皮肤美容术,在治疗光老化方面具有很大优势.     

Split-face模式评价强脉冲光治疗面部光老化的疗效

皮肤光老化为日光曝露部位皮肤出现的特有的外观和组织学变化[1].强脉冲光(intense pulsed light,IPL)技术作为新一代非剥脱性皮肤美容术,在治疗光老化方面具有很大优势.     

Split-face模式评价强脉冲光治疗面部光老化的疗效

皮肤光老化为日光曝露部位皮肤出现的特有的外观和组织学变化[1].强脉冲光(intense pulsed light,IPL)技术作为新一代非剥脱性皮肤美容术,在治疗光老化方面具有很大优势.     

Split-face模式评价强脉冲光治疗面部光老化的疗效

皮肤光老化为日光曝露部位皮肤出现的特有的外观和组织学变化[1].强脉冲光(intense pulsed light,IPL)技术作为新一代非剥脱性皮肤美容术,在治疗光老化方面具有很大优势.     

Skin rejuvenating effects of chemical peeling: a study in photoaged hairless mice

Background Chemical peeling is a dermatologic treatment for skin aging. However, the mechanism by which the chemical peel achieves its results is not clear. We investigated the effects of chemical peeling and the mechanism of wrinkle reduction in photoaged hairless mice skin. Methods After inducing photoaged skin in hairless mice by repetitive ultraviolet‐B irradiation applied over 14 weeks, we applied trichloroacetic acid (TCA) 30%, TCA 50%, and phenol on areas of the same size on the backs of the mice. Punch biopsies were obtained 7, 14, 28, and 60 days after the procedure for histologic and immunohistochemical analyses. Results Histologic examination showed an increase in dermal thickness, collagen fibers, and elastic fibers in the dermis of intervention groups compared with control groups. These increases were maintained significantly for 60 days. Conclusions This study demonstrates that chemical peeling reduces wrinkles and regenerates skin by increasing dermal thickness and the amount of collagen and elastic fibers in photoaged skin.     

Retinoids suppress cysteine-rich protein 61 (CCN1), a negative regulator of collagen homeostasis, in skin equivalent cultures and aged human skin in vivo

Alterations in connective tissue collagen are prominent features of both chronologically aged and photoaged (ageing because of sun exposure) human skin. These age-related abnormalities are mediated in part by cysteine-rich protein 61 (CCN1). CCN1 is elevated in the dermis of both chronologically aged and photoaged human skin in vivo and promotes aberrant collagen homeostasis by down-regulating type I collagen, the major structural protein in skin, and promoting collagen degradation. Vitamin A and its metabolites have been shown to improve chronologically aged and photoaged skin by promoting deposition of new collagen and preventing its degradation. Here, we investigated regulation of CCN1 expression by retinoids in skin equivalent cultures and chronologically aged and photoaged human skin in vivo. In skin equivalent cultures, all-trans retinoic acid (RA), the major bioactive form of vitamin A in skin, significantly increased type I procollagen and reduced collagenase (matrix metalloproteinases-1, MMP-1). Addition of recombinant human CCN1 to skin equivalent cultures significantly reduced type I procollagen and increased MMP-1. Importantly, RA significantly reduced CCN1 expression in skin equivalent cultures. Topical treatment with retinol (vitamin A, 0.4%) for 7days significantly reduced CCN1 mRNA and protein expression in both chronologically aged (80+years) and photoaged human skin in vivo, compared to vehicle-treated skin. These data indicate that the mechanism by which retinoids improve aged skin, through increased collagen production, involves down-regulation of CCN1.     

K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin

Sphingosine-1-phosphate (S1P), which is formed by phosphorylation of sphingosine through a process catalysed by sphingosine kinase (SK), is a multifunctional mediator of a variety of cellular responses including proliferation, differentiation, motility, and survival. K6PC-5, which was recently synthesized as a novel SK activator, is expected to increase S1P levels. Indeed studies have already demonstrated that K6PC-5 exhibits anti-aging effects on intrinsic aged murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and epidermal differentiation. However, photoaging and intrinsic aging have highly different clinical and histopathological properties. In this study, we developed a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC-5, as an SK activator, had anti-aging effects on photoaged murine skin in addition to its effects on intrinsic aged murine skin and determined the mechanism. K6PC-5 increased dermal collagen density in photoaged skin through increases in fibroblasts and collagen production. Photoaged murine skin treated with K6PC-5 showed an increase in stratum corneum (SC) integrity with increased corneodesmosome density and an improvement in barrier recovery rate. Matrix metalloproteinase 13 remained unchanged. These results indicate that topical application of K6PC-5 improves photoaged skin by improving skin barrier and increasing fibroblast count and function. In conclusion, K6PC-5, as an S1P activator, improves long-term UV-exposed aged skin as well as intrinsic aged skin.     

Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.

To the best of our knowledge, no study has been conducted to date to directly compare the collagen metabolism of photoaged and naturally aged human skin. In this study, we compared collagen synthesis, matrix metalloproteinase-1 levels, and gelatinase activity of sun-exposed and sun-protected skin of both young and old subjects. Using northern blot analysis, immunohistochemical stain, and Western blot analysis, we demonstrated that the levels of procollagen type I mRNA and protein in photoaged and naturally aged human skin in vivo are significantly lower than those of young skin. Furthermore, we demonstrated, by northern blot analysis, that the procollagen alpha1(I) mRNA expression of photoaged skin is much greater than that of sun-protected skin in the same individual. In situ hybridization and immunohistochemical stain were used to show that the expression of type I procollagen mRNA and protein in the fibroblasts of photoaged skin is greater than for naturally aged skin. In addition, it was found, by Western blot analysis using protein extracted from the dermal tissues, that the level of procollagen type I protein in photoaged skin is lower than that of naturally aged skin. The level of matrix metalloproteinase-1 protein and the activity of matrix metalloproteinase-2 were higher in the dermis of photoaged skin than in naturally aged skin. Our results suggest that the natural aging process decreases collagen synthesis and increases the expression of matrix metalloproteinases, whereas photoaging results in an increase of collagen synthesis and greater matrix metalloproteinase expression in human skin in vivo. Thus, the balance between collagen synthesis and degradation leading to collagen deficiency is different in photoaged and naturally aged skin.     

H2O2 accumulation by catalase reduction changes MAP kinase signaling in aged human skin in vivo

To understand the molecular alterations occurring during the aging process, we compared mitogen-activated protein (MAP) kinase activities in the intrinsically aged and photoaged skins in the same individuals. Furthermore, we investigated the molecular events related to MAP kinase changes in intrinsically aged and photoaged skins. We found that extracellular-signal-regulated kinase (ERK) activity in photoaged skin was reduced, and that the activities of c-Jun N-terminal kinase (JNK) and p38 kinase were increased compared with intrinsically aged skin in the same individuals. Phospho-c-Jun levels and activator protein 1 activities in photoaged skin were also higher than in intrinsically aged skin. Moreover, catalase activity was found to be much reduced in primary dermal fibroblasts from photoaged skin, and as a result, H2O2 accumulated more in primary dermal fibroblasts in photoaged skin. In addition, treating primary dermal fibroblasts from photoaged skin with catalase reduced H2O2 levels, reversed aging-dependent MAP kinase changes, and inhibited matrix metalloproteinase (MMP)-1 expression. Our results indicate that the accumulation of reactive oxygen species due to catalase attenuation may be a critical aspect of the MAP kinase signaling changes that may lead to skin aging and photoaging in human skin in vivo. Thus, the induction and regulation of endogenous antioxidant enzymes including catalase may offer a strategy for preventing and treating skin aging.     

Repair of photoaged dermal matrix by topical application of a cosmetic 'antiageing' product

BACKGROUND: Photoaged skin is characterized by coarse and fine wrinkles. The mechanism of wrinkle formation appears to involve changes to components of the dermal extracellular matrix. Topical treatment with all-trans retinoic acid (RA) can repair photoaged dermal matrix; this is regarded as the 'gold standard' against which repair agents are judged. To date, little is known regarding the ability of over-the-counter 'antiageing' products to repair photoaged skin. OBJECTIVES: We used a modified occluded patch test to ascertain whether topical applications of cosmetic 'antiageing' products are able to repair photoaged human skin. METHODS: Commercially available test products [basic moisturizer, 'antiageing' cream containing different active complex levels (6% active: lipopentapeptide, white lupin peptides, antioxidants, retinyl palmitate; 2% active: lipopentapeptide, white lupin peptides, antioxidants)] were applied under occlusion for 12 days prior to biopsy and histological assessment in photoaged volunteers (n=9). RA was used as a positive control. RESULTS: In agreement with previous studies, the patch-test study revealed that RA produced significant fibrillin-1 deposition in the papillary dermis (P<0.01) but had little effect on procollagen I or matrix metalloproteinase-1 expression. The 6% total active complex formulation, however, increased the deposition of fibrillin-1 and procollagen I (P<0.01, P<0.05, respectively). CONCLUSIONS: This study indicates that in an in vivo 12-day patch test an over-the-counter cosmetic product can induce changes in photoaged dermal extracellular matrix, which are indicative of repair.     

Fibrillin-rich microfibrils are reduced in photoaged skin. Distribution at the dermal-epidermal junction

Chronic sun exposure results in photoaged skin with deep coarse wrinkles and loss of elasticity. We have examined the distribution and abundance of fibrillin-rich microfibrils, key structural components of the elastic fiber network, in photoaged and photoprotected skin. Punch biopsies taken from photoaged forearm and from photoprotected hip and upper inner arm of 16 subjects with a clinical range of photoaging were examined for fibrillin-1 and fibrillin-2 expression and microfibril distribution. In situ hybridization revealed decreased fibrillin-1 mRNA but unchanged fibrillin-2 mRNA levels in severely photoaged forearm biopsies relative to photoprotected dermal sites. An immunohistochemical approach demonstrated that microfibrils at the dermal-epidermal junction were significantly reduced in moderate to severely photoaged forearm skin. Confocal microscopy revealed that the papillary dermal microfibrillar network was truncated and depleted in photoaged skin. These studies highlight that the fibrillin-rich microfibrillar network associated with the upper dermis undergoes extensive remodeling following solar irradiation. These changes may contribute to the clinical features of photoaging, such as wrinkle formation and loss of elasticity.     

Cosmeceuticals: focus on topical retinoids in photoaging

Evidence from a randomized clinical trial showed that, in spite of the many surgical procedures effective in ameliorating the clinical appearance of photoaged skin, the only medical therapy with proven benefits in photoaged skin are topical retinoids, in particular tretinoin, isotretinoin, and tazarotene. The application of retinoids might not only clinically and biochemically repair photoaged skin, but their use might also prevent photoaging. Furthermore, new evidence suggests a beneficial role of topical retinoids in the treatment of intrinsically aged skin.     

Effects of 12-O-tetradecanoyl-phorbol-13-acetate [corrected] and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged human keratinocytes.

Skin aging may be divided into photoaging and intrinsic aging. The purpose of this study was to investigate the effects of 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate on the production and expression of cytokines and proto-oncogenes in photoaged and intrinsically aged skin, compared with young skin. Keratinocytes were taken from newborns, young adults in their twenties, and from the forearm and thigh of volunteers in their fifties and seventies. Interleukin-1alpha and -6, and interleukin-1 receptor antagonist, c-fos and c-myc were measured after cultured keratinocytes had been treated with 12-O-tetradecanoyl-phorbol-13-acetate and sodium lauryl sulfate. There has been no report concerning the dependence of cytokine production by sodium lauryl sulfate upon photoaging and intrinsic aging. This study also involves the first investigation of the effects of aging on c-myc expression by 12-O-tetradecanoyl-phorbol-13-acetate treatment. Cytokine production decreased markedly with age. These results suggest the progressive decline of cellular function with age. The ratio of cytokine production in the irritant-treated group compared with that in the control group showed a different pattern in photoaging and intrinsic aging. With the significant difference between photoaging and intrinsic aging, T/C ratio decreased in interleukin-1alpha and interleukin-1 receptor antagonist upon aging, whereas it increased in interleukin-6. S/C ratio was uniquely elevated on photoaged skin in the 50 y age group. It is suggested that photoaged skin shows an exaggerated reaction to surfactant. Compared with the control, c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes decreased with age in the thigh, but increased in the photoaged skin of forearm. The increased c-fos expression in 12-O-tetradecanoyl-phorbol-13-acetate-treated keratinocytes could be relevant for the predisposition of photoaged keratinocytes to malignant transformation.     

Effects of moisturization on epidermal homeostasis and differentiation

Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine.