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自由基与衰老及帕金森氏病 总被引:7,自引:0,他引:7
随着人们对导致衰老及相关疾病(帕金森氏病)的各种因素的研究不断深入,认为随机体年龄的增加,线粒体氧化磷酸化系统中产生的自由基逐渐增多,并累积到一定程度,促成了衰老及相关疾病的形成的理论,越来越引起人们广泛的关注。本文就当前关于自由基与衰老的成因、帕金森氏病的关系的研究进展作了简要概括。 相似文献
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采用目前公认的DNA氧化损伤标志物8-OHdG的单抗,利用LSAB法研究不同年龄组BALB/C小鼠胸腺和脾脏8-OHdG的生成水平,对免疫组织在衰老过程中DNA氧化损伤的水平进行免疫组织化学研究。以探讨免疫系统的自由基损伤对衰老的影响。结果表明,在胸腺,8-OHdG^ 细胞密度随增龄而增多,并主要位于髓质区;脾脏中的阳性细胞则无明显的增龄性变化,但胸染形态却存在明显差异。本研究结果显示,衰老过程中,免疫细胞内8-OHdG含量发生改变,免疫系统受到了氧自由基的损伤。8-OHdG可作为免疫老化过程中的一种生物标志。 相似文献
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目的:探讨有氧运动对衰老大鼠骨骼肌线粒体能量代谢的影响。方法:将20只12月龄的雌性Wistar大鼠随机分为老年安静组(AC,n=10)及老年运动组(AE,n=10),另取10只2月龄的雌性Wistar大鼠为青年安静组(YC,n=10);安静组大鼠进行正常饲养,运动组大鼠进行坡度为5°,速度为15.2 m/min,第1天运动15 min、第2天运动30 min、从第3天开始每天运动45 min,每周6 d,共12周。12周后所有大鼠断头处死,取腓肠肌样本,差速离心法提取线粒体,测定SOD和GSH-Px活性、MDA含量、三羧酸循环限速酶(CS、ICD和α-KGDHC)活性及呼吸链酶复合体(RCCⅠ~Ⅳ)活性。结果:①与YC组相比,AC组骨骼肌线粒体SOD活性和MDA含量显著增加(P<0.05),CS和α-KGDHC活性均显著降低(P<0.05),RCCⅠ、RCCⅡ和RCCⅣ活性均显著下降(P<0.05),RCCⅢ活性显著升高(P<0.05);AE组骨骼肌线粒体SOD、GSH-Px活性和MDA含量均显著增加(P<0.01),CS、ICD和α-KGDHC活性均显著升高(P<0.01),RCCⅠ~Ⅳ活性均显著升高(P<0.01)。②与AC组相比,AE组骨骼肌线粒体SOD、GSH-Px活性均显著升高(P<0.05),MDA含量显著下降(P<0.05),CS、ICD、α-KGDHC和RCCⅠ~Ⅳ活性均显著升高(P<0.01)。结论:有氧运动可以提高老年大鼠骨骼肌线粒体抗氧化能力,降低脂质过氧化水平,提高三羧酸循环及呼吸链功能,促进线粒体能量代谢,延缓衰老过程中线粒体的退行性变化。 相似文献
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随人口老龄化进程加速,由心脏衰老引发的各类心血管疾病已成为不可忽略的健康问题。心脏中,约95%的ATP来源于心肌线粒体,以维持心脏泵血功能。线粒体功能障碍可导致心肌能量不足,心肌细胞受损死亡或心肌衰老。因此,线粒体的功能完好对于维持心脏正常功能具有重要作用,并被认为是心脏衰老的一个关键特征。本文对心脏衰老与线粒体功能障碍进行综述,主要概述了衰老心脏的特征,衰老心肌细胞线粒体结构与功能的变化,重点阐述线粒体功能障碍导致心脏衰老的5大因素,包括线粒体形态数量的改变,线粒体DNA突变,线粒体质量控制失败,线粒体酶的改变,线粒体相关代谢产物及应激信号的变化。总结了靶向线粒体的心脏衰老治疗方式及作用机制,同时探讨了靶向年龄相关的线粒体治疗心脏衰老的现状和未来方向。 相似文献
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裂叶牵牛花在一日内开放过程中,花的 SOD 活性、TBA 物质的含量均发生显著性的变化。结果表明:SOD 活性随开花时间的延长而降低(P<0.01),TBA 物质含量上升(P<0.01),花直径变小(P<0.01),花的鲜重下降(P<0.01)。提示:牵牛花的衰老可能与自由基有密切关系。 相似文献
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鼠毛及脑线粒体DNA片段缺失与增龄的关系 总被引:10,自引:0,他引:10
以聚合酶链反应(PCR)技术检测不同年龄Balb/c小鼠脑细胞线粒体DNA片段缺失与增龄的关系.发现老年鼠脑细胞线粒体3867bp片段缺失率为50%;而断奶鼠与青年鼠均无此缺失片段出现;用鼠毛为材料进行无损伤检测亦获类似的结果.有人认为线粒体DNA片段缺失率可作为生物衰老的一种生物学标志 相似文献
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Takayuki Ozawa 《Bioscience reports》1997,17(3):237-250
The molecular genetics and bioenergetics of oxidative damage, fragmentation, and fragility of mitochondrial DNA in cellular apoptosis is reviewed in connection with the redox mechanism of ageing. 相似文献
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Dietary Restriction at Old Age Lowers Mitochondrial Oxygen Radical Production and Leak at Complex I and Oxidative DNA Damage in Rat Brain 总被引:8,自引:0,他引:8
Sanz A Caro P Ibañez J Gómez J Gredilla R Barja G 《Journal of bioenergetics and biomembranes》2005,37(2):83-90
Previous studies in mammalian models indicate that the rate of mitochondrial reactive oxygen species ROS production and the ensuing modification of mitochondrial DNA (mtDNA) link oxidative stress to aging rate. However, there is scarce information concerning this in relation to caloric restriction (CR) in the brain, an organ of maximum relevance for ageing. Furthermore, it has never been studied if CR started late in life can improve those oxidative stress-related parameters. In this investigation, rats were subjected during 1 year to 40% CR starting at 24 months of age. This protocol of CR significantly decreased the rate of mitochondrial H2O2 production (by 24%) and oxidative damage to mtDNA (by 23%) in the brain below the level of both old and young ad libitum-fed animals. In agreement with the progressive character of aging, the rate of H2O2 production of brain mitochondria stayed constant with age. Oxidative damage to nuclear DNA increased with age and this increase was fully reversed by CR to the level of the young controls. The decrease in ROS production induced by CR was localized at Complex I and occurred without changes in oxygen consumption. Instead, the efficiency of brain mitochondria to avoid electron leak to oxygen at Complex I was increased by CR. The mechanism involved in that increase in efficiency was related to the degree of electronic reduction of the Complex I generator. The results agree with the idea that CR decreases aging rate in part by lowering the rate of free radical generation of mitochondria in the brain. 相似文献
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《Free radical research》2013,47(3-6):121-128
Progress in identifying the important endogenous processes damaging DNA and developing methods to assay this damage in individuals is presented. This approach may aid studies on modulation of cancer and aging.The endogenous background level of oxidant-induced DNA damage in vivo has been assayed by measuring 8-hydroxydeoxyguanosine (oh8dG), thymine glycol and thymidine glycol in urine and oh8dG in DNA. oh8dG is one of about 20 adducts found on oxidizing DNA, e.g., by radiation. The level of oxidative DNA damage as measured by oh8dG in normal rat liver is shown to be extensive, especially in mtDNA (1/130,000 bases in nuclear DNA and 1/8,000 bases in mitochondrial DNA). We also discuss three hitherto unrecognized antioxidants in man. 相似文献
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Previous studies have shown that caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat organs, which can be linked to the slowing of aging rate induced by this regime. These two characteristics are also typical of long-lived animals. However, it has never been investigated if those decreases are linked to the decrease in the intake of calories themselves or to decreases in specific dietary components. In this study the possible role of the dietary protein was investigated. Using semipurified diets, the ingestion of proteins of Wistar rats was decreased by 40% below that of controls while the other dietary components were ingested at the same level as in animals fed ad libitum. After seven weeks in this regime the liver of the protein restricted animals showed 30–40% decreases in mitochondrial production of reactive oxygen species (ROS) and in oxidative damage to nuclear and mitochondrial DNA. The decreases in ROS generation occurred specifically at complex~I. They also occurred without changes in mitochondrial oxygen consumption. Instead, there was a decrease in the percent free radical leak (the percentage of total electron flow leading to ROS generation in the respiratory chain). These results are strikingly similar to those previously obtained after 40% caloric restriction in the liver of Wistar rats. Thus, the results suggest that part of the decrease in aging rate induced by caloric restriction can be due to the decreased intake of proteins acting through decreases in mitochondrial ROS production and oxidative DNA damage. Interestingly, these tissue oxidative stress-linked parameters can be lowered by restricting only the intake of dietary protein, probably a more feasible option than caloric restriction for adult humans. 相似文献
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Stephanie Lazo Nicole Noren Hooten Jamal Green Erez Eitan Nicolle A. Mode Qing‐Rong Liu Alan B. Zonderman Ngozi Ezike Mark P. Mattson Paritosh Ghosh Michele K. Evans 《Aging cell》2021,20(1)
The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell‐free mtDNA (ccf‐mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30–400 nm), lipid‐bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems. Here, we report that a portion of ccf‐mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30–64 years cross‐sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV‐derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age‐dependent manner. 相似文献
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Free Radical-Induced Tandem Base Damage in DNA Oligomers 总被引:6,自引:0,他引:6
Harold C Box Edwin E Budzinski Jean B Dawidzik Jason S Gobey Harold G Freund 《Free radical biology & medicine》1997,23(7):1021-1030
A new tandem base lesion has been identified in two DNA oligomers, namely d(GpT) and d(CpGpTpA), exposed to X-irradiation in deoxygenated aqueous solution. In this lesion the C6 carbon atom of thymine is hydroxylated and a covalent link is formed between the C5 carbon atom of thymine and the C8 carbon atom of the adjacent guanine base. In addition, further evidence in the form of mass spectrometric data is presented confirming the structures of previously reported tandem base lesions that are produced by ionizing radiation in the presence of oxygen. New data is presented on the prevalence of a previously reported tandem base lesion in which the methyl carbon atom of thymine is covalently linked to the C8 carbon atom of the adjacent guanine base. The free radical-initiated processes by which tandem base damages are generated are discussed. To date four different radiation-induced tandem base lesion have been identified. The evidence suggests that tandem base damage is a significant component of free radical-induced DNA damage. 相似文献
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人mtDNA比核DNA更易受到自由基的氧化损伤,这些损伤可以被线粒体内的DNA修复机制所修复,损伤与修复是决定突变是否产生的两个重要因素.为了确定氧化损伤与损伤后修复对mtDNA突变的具体影响,采用四氧嘧啶处理LO2细胞,这种试剂进入细胞后,经氧化还原反应生成的自由基与线粒体自身代谢产生的自由基类似,然后观察自由基对细胞mtDNA的氧化损伤与损伤后DNA修复的动力学变化.由于线粒体的正常功能为修复机制所必需,采用MTT细胞活力实验检测不同浓度四氧嘧啶处理下线粒体酶活力,发现9 mmol/L四氧嘧啶培养细胞1h后,线粒体琥珀酸脱氢酶功能在撤去药物后0,2,8和24 h时间点均无明显变化.提取各组细胞的mtDNA,用EndoⅢ和Fgp两种酶切除受氧化损伤的核苷酸,然后用碱性琼脂糖凝胶电泳分离大小不等的mtDNA,进行DNA印迹实验,地高辛-抗体-碱性磷酸酶系统显色,检测完整与断裂的mtDNA量,利用Poisson公式(s=-lnP0/P,P0为未断裂链光密度值,P为所有链光密度值总和)计算一个mtDNA分子的平均损伤频率,结果显示,9 mmol/L四氧嘧啶处理细胞1 h,链平均损伤频率由对照的0.11个/分子增加至5.60个/分子,明显增加了mtDNA上核苷酸的氧化损伤,除去药物后8 h,绝大部分损伤可被修复,损伤频率减至0.40个/分子,除去药物后24 h核苷酸的氧化损伤恢复至正常水平.采用接头介导PCR(LM-PCR)检测MTTL1基因区域内单个核苷酸的损伤与修复动力学.这种方法可以检测各组mtDNA上MTTL1基因75 bp区域内单个核苷酸损伤的部位及频率.结果显示,人MTTL1基因存在20个易受氧化损伤的核苷酸热点,经与相应区域内文献报道的16个突变热点比较,有12个热点部位重合,而修复未显示热点部位或区域.结果提示,自由基对核苷酸的选择性氧化损伤是决定mtDNA点突变发生及发生部位的主要原因. 相似文献