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胰岛素样生长因子-1通过调控核内p53-progerin通路减轻肝细胞衰老 被引量:2
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作者 江小柯 李俊 +9 位作者 白阳秋 丁辉 杨志煜 孙锁锋 梁园 彭聪 韩双印 李修岭 罗晓英 张炳勇 《中华肝脏病杂志》 CSCD 北大核心 2021年第3期271-274,共4页
H_(2)O_(2)刺激原代肝细胞构建细胞衰老模型,采用p53 siRNA、早衰蛋白(pmgerin)siRNA或胰岛素样生长因子(IGF)-1腺病毒载体转染原代肝细胞,检测β-半乳糖背酶染色阳性细胞数及p53、progerin的表达。结果显示,p53 siRNA和progerin siRNA... H_(2)O_(2)刺激原代肝细胞构建细胞衰老模型,采用p53 siRNA、早衰蛋白(pmgerin)siRNA或胰岛素样生长因子(IGF)-1腺病毒载体转染原代肝细胞,检测β-半乳糖背酶染色阳性细胞数及p53、progerin的表达。结果显示,p53 siRNA和progerin siRNA敲低p53和progerin的表达,肝细胞衰老减轻;转染IGF-1腺病毒载体至原代肝细胞过表达IGF-1,β-半乳糖背酶阳性细胞数减少,细胞核中p53和progerin表达下调、细胞质中p53表达上调;p53与progerin共沉淀及共定位于肝细胞核区减少。过表达IGF-1可通过抑制p53核转位,减少核内p53-progerin相互作用,减轻肝细胞衰老。 展开更多
关键词 胰岛素样生长因子 肝细胞衰老 P53 早衰蛋白
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Anti-Aging Efficacy of a New Alendronate-Pravastatin Cosmetic Combination: A Randomized Double Blind Comparative Study
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作者 Bénédicte Cantecor Marie-Pierre Savelli +4 位作者 Marie-Pierre Savelli Philippe Piccerelle Nicolas Lévy Vincent Bonniol Pierre Cau 《Journal of Cosmetics, Dermatological Sciences and Applications》 2013年第3期163-171,共9页
Progeria is a rare genetic disease that causes accelerated aging and death in children at a mean age of 13.5 years. An?aminobisphosphonate-statin combination has been shown to reduce the toxicity of the mutated protei... Progeria is a rare genetic disease that causes accelerated aging and death in children at a mean age of 13.5 years. An?aminobisphosphonate-statin combination has been shown to reduce the toxicity of the mutated protein, progerin, in progeria patient cell cultures and in a mouse model of the disease. This combination is currently being tested in a European Therapeutic Trial for progeria in Marseille (ClinicalTrials.gov identifier NCT00731016). Progerin has been shown to be produced by skin cells during physiological aging. The objective of this study was to assess the efficiency of a new and original cosmetic formulation containing alendronate and pravastatin sodium salts, reduce crow’s feet wrinkles, and cheek hollow in a double blind, randomized and placebo controlled comparative study. Three cosmetic preparations were evaluated using Fast Optical in vivo Topometry of human Skin (FOITS): one containing sodium alendronate and sodium pravastatin, a placebo, and a commercial anti-aging product. Fifty-seven female and twenty-five male volunteers between 51 and 71-year-old were selected. Each subject tested two of the three products once a day, in the evening, by spreading each selected product on one side of the face. Skin micro-relief was analyzed at 0, 28, 56 and 84 days. Statistical analysis of 7 clinical qualitative (left or right side of face, gender, and 3 skin types) and 6 quantitative parameters (age, weight at each test time, wrinkle clinical grade at inclusion time) showed no statistical differences between the three tested products. In contrast, most of the 8 quantitative FOITS parameters describing skin micro-relief were statistically improved by the alendronate-pravastatin combination compared to the placebo or to the commercial anti-aging product. A cosmetic preparation containing alendronate and pravastatin sodium salts exhibited anti-aging effects by reducing crow’s feet wrinkles and restoring cheek volume. 展开更多
关键词 Skin Aging progerin STATIN Aminobisphosphonate Double Blind Comparative Clinical Study PLACEBO FOITS
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雷帕霉素诱导细胞自噬在衰老相关疾病中的作用 被引量:17
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作者 吴伯艳 刘新光 陈维春 《中国药理学通报》 CAS CSCD 北大核心 2015年第1期11-14,共4页
哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)是衰老和衰老相关疾病的一个关键调节因子。雷帕霉素(rapamycin,RAPA)可通过抑制m TOR通路,诱导和促进细胞自噬的发生。细胞自噬是维持细胞内稳态的主要方式与途径,通过降... 哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)是衰老和衰老相关疾病的一个关键调节因子。雷帕霉素(rapamycin,RAPA)可通过抑制m TOR通路,诱导和促进细胞自噬的发生。细胞自噬是维持细胞内稳态的主要方式与途径,通过降解多余的、受损的及衰老的蛋白与细胞器,为细胞重建、再生和修复提供必需原料。早老症(hutchinson-gilford progeria syndrome,HGPS)患者细胞中伴随早老蛋白(progerin)的异常聚集;此外,诸如亨廷顿病、帕金森病、阿尔茨海默病等神经退行性疾病细胞内同样出现异常蛋白质的聚集,而这些异常蛋白的清除正依赖于细胞的自噬作用。由此可见,雷帕霉素是潜在的抗衰老、治疗早老症及衰老相关疾病的重要药物。该文主要阐述雷帕霉素促进细胞自噬方面的功能及在HGPS、神经退行性疾病方面的应用。 展开更多
关键词 雷帕霉素 雷帕霉素靶蛋白 自噬 早老症 早老蛋白 神经退行性疾病
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Telomere Protective Effects of a Cyanobacteria Phycocyanin against Blue Light and UV Irradiations: A Skin Anti-Aging and Photo-Protective Agent
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作者 Francine Joly Jean-Eric Branka +1 位作者 Eric Darnis Luc Lefeuvre 《Journal of Cosmetics, Dermatological Sciences and Applications》 2019年第4期336-345,共10页
Background: Cyanobacteria phycocyanins (Cps) have already shown powerful antioxidant properties. In human cells submitted to oxidative stress the telomeres length decrease, the expression of progerin and the activity ... Background: Cyanobacteria phycocyanins (Cps) have already shown powerful antioxidant properties. In human cells submitted to oxidative stress the telomeres length decrease, the expression of progerin and the activity of mTOR are increased. At our knowledge, there is no published data on Cps correlated with ultraviolet radiation (UV) and blue light effects in human cells regarding telomeres’ length, progerin expression or mTOR1 complex activity. Objectives: In this study, we sought to assess 1) telomeres’ length in newborn human fibroblasts exposed to UV and blue light;2) progerin production in mature human normal fibroblasts exposed to UV;3) mTOR1 activation in adult human normal keratinocytes exposed to UV, analyzing the activity of a Cyanobacteria phycocyanin (Cp) in these in vitro models. Materials and Methods: Human skin fibroblasts or human normal keratinocytes were cultured—in the absence or in the presence of Cp and submitted to UVB + UVA and blue light irradiations. Telomeres’ length, progerin expression and mTOR1 activity were then assessed by molecular biology and immuno-enzymatic methods. Results: In cultured fibroblasts exposed to irradiations and treated by Cp, telomeres’ shortage and progerin expression were lower compared to irradiated untreated cells. In cultured keratinocytes treated by Cp and exposed to irradiations, the mTOR activity was lower compared to irradiated untreated cells. Conclusions: In these in vitro studies on human skin fibroblasts and on normal human keratinocytes, the cyanobacteria phycocyanin (Cp) showed a decrease of damages induced by UV and blue light expressed by telomeres preservation and downregulation of progerin expression and of mTOR activity, thus showing skin anti-aging and photo-protective potential. 展开更多
关键词 CYANOBACTERIA Phycocyanins UVA UVB Blue Light TELOMERE Length TELOMERE Shortage progerin Production mTOR1 Activity Human SKIN Cells Aging/Photo-Aging
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早老素导致基因组不稳定的机制 被引量:2
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作者 胡晓婷 刘新光 陈维春 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2019年第8期843-849,共7页
基因组不稳定(genomic instability)是机体衰老的标志之一,也是儿童早老症(HutchinsonGilford progeria syndrome,HGPS)患者细胞的典型特征。HGPS的发生与早老素(progerin)堆积密切相关,但早老素如何引起基因组不稳定尚缺乏系统性的阐... 基因组不稳定(genomic instability)是机体衰老的标志之一,也是儿童早老症(HutchinsonGilford progeria syndrome,HGPS)患者细胞的典型特征。HGPS的发生与早老素(progerin)堆积密切相关,但早老素如何引起基因组不稳定尚缺乏系统性的阐述。基因组的结构稳定与DNA的正确复制、DNA损伤修复、端粒的维持和稳定以及表观遗传学修饰密切相关。本文主要讨论早老素在改变正常核纤层结构的基础上,通过影响相关通路关键蛋白质的水平或者定位,引起细胞内氧化应激增强、DNA复制应激和DNA损伤修复障碍,细胞DNA损伤增多和端粒的加速缩短,并在改变组蛋白甲基化和乙酰化方面导致基因组不稳定的机制。 展开更多
关键词 早老素 DNA损伤修复 基因组不稳定 端粒 表观遗传
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早老症
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作者 彭斌 耿松梅 《皮肤科学通报》 2020年第1期106-114,共9页
早老症极其罕见,是一种由核纤层蛋白A(LMNA)基因突变引起的散发性常染色体显性遗传疾病。LMNA突变产生法尼基化的早老蛋白在不同组织中累积,引起过早衰老的特征性表现,包括硬皮病样皮肤改变、脱发、头皮静脉显露、骨关节异常和动脉粥样... 早老症极其罕见,是一种由核纤层蛋白A(LMNA)基因突变引起的散发性常染色体显性遗传疾病。LMNA突变产生法尼基化的早老蛋白在不同组织中累积,引起过早衰老的特征性表现,包括硬皮病样皮肤改变、脱发、头皮静脉显露、骨关节异常和动脉粥样硬化。患者平均在14.6岁时死于心肌梗塞或卒中。本文会描述早老症的历史、发病机制、流行病学、临床特征、以及目前的治疗方法。对早老症的研究有助于我们对生理性衰老的理解。 展开更多
关键词 早老症 早老蛋白 衰老
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早老素通过下调CDK4使HEK293T细胞周期阻滞
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作者 宋浩昌 余辉 +1 位作者 刘新光 陈维春 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2018年第1期96-102,共7页
早老素(progerin)的累积导致儿童早老症(Hutchinson-Gilford progeria syndrome,HGPS)的发生,并与正常衰老相关。早老素能使细胞内稳态失衡但分子机制仍有待深入研究。本研究旨在探讨早老素导入人胚胎肾293T细胞(human embryo kidney 29... 早老素(progerin)的累积导致儿童早老症(Hutchinson-Gilford progeria syndrome,HGPS)的发生,并与正常衰老相关。早老素能使细胞内稳态失衡但分子机制仍有待深入研究。本研究旨在探讨早老素导入人胚胎肾293T细胞(human embryo kidney 293T cell,HEK293T)后细胞增殖、周期变化的分子机制。形态学观察发现过表达早老素的HEK293T细胞密度下降,(57±2.47)%细胞核形态皱缩。细胞增殖和周期实验证明早老素使细胞增殖减慢,发生G1/S期阻滞,G1细胞从(42.3±1.31)%升至(47.2±1.26)%,而S期细胞从(43.1±1.36)%降至(38.5±1.42)%。Western印迹结果显示早老素的高表达引起p21蛋白表达上调(103.2±1.49)%,CDK4下调(63±1.52)%,而p53、ATM、Cyclin E1以及p16等蛋白质水平均不变;HEK293T细胞中早老素的过表达导致γ-H2AX水平下调(53±1.36)%,H2O2处理后变化趋势不变。我们的研究结果提示,早老素通过上调p21和下调CDK4使细胞发生周期阻滞,不能增加HEK293T细胞的损伤及衰老。 展开更多
关键词 早老症 早老素 人胚胎肾293T细胞 细胞周期阻滞 衰老
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雷帕霉素或可延缓早老综合征患者疾病进程
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作者 杨臻峥(编译) 《药学进展》 CAS 2011年第7期F0003-F0003,共1页
据《科学一转化医学》杂志(Science Translational Medicine)于2011年6月29日报道,美国国立卫生研究院(National Institutes of Health,NIH)人类基因组研究中心、马里兰大学细胞生物学和分子遗传学系以及哈佛大学麻省总医院(MGH... 据《科学一转化医学》杂志(Science Translational Medicine)于2011年6月29日报道,美国国立卫生研究院(National Institutes of Health,NIH)人类基因组研究中心、马里兰大学细胞生物学和分子遗传学系以及哈佛大学麻省总医院(MGH)神经科的研究人员发现,大环内酯类免疫抑制剂雷帕霉素(rapamycin)或可用于治疗早老综合征(Hutchinson—Gilford progeria syndrome,HGPS,也称早衰症)。 展开更多
关键词 早老综合征 雷帕霉素 LMNA基因 progerin
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