槲皮素对线虫抗衰老的影响及其机制的初步研究

以秀丽线虫作为研究体内抗衰老作用的模型生物,研究槲皮素抗衰老作用及其机制.通过对秀丽线虫上进行的寿命分析实验、生殖能力测试和压力应激测试所得指标,探讨槲皮素延缓线虫衰老的作用机理.结果表明,高剂量的槲皮素组能显著延长线虫的平均寿命和最大寿命百分率分别为35.97%、20%(p<0.001),对其生殖能力没有损害.提高线...     

秀丽隐杆线虫免疫衰老指标的建立

秀丽隐杆线虫是研究衰老的重要模式生物,但目前对其免疫衰老的研究缺乏评价指标。建立了秀丽隐杆线虫-铜绿假单胞菌感染模型,考察了线虫抗感染免疫能力与衰老之间的关系,建立了线虫免疫衰老的评价指标。首先用铜绿假单胞菌感染线虫建立模型,将处于不同衰老程度的线虫用于感染实验,考察了线虫感染后的生存时间与衰老程度的关系;将感染后的生存时间作为抗感染免疫衰老的指标,其结果与线虫抗氧化能力和寿命指标的结果相互印证。结果显示,7 d、14 d、21 d龄的线虫感染后的生存时间依次减少,与抗氧化能力的衰退情况相符;与野生型相比,长寿线虫(daf-2突变线虫)感染后的生存时间延长,短寿线虫(daf-16突变线虫)感染后的生存时间缩短,线虫的抗感染免疫指标与寿命指标结果相符;能延长线虫寿命的化合物酪氨酸也延长了线虫感染后的生存时间。因此线虫-铜绿假单胞菌感染模型可以用于评价线虫的免疫衰老,感染后线虫的生存时间可作为免疫衰老的评价指标。     

多球壳菌素延长裂殖酵母细胞寿命可能机制研究

寻找抗衰老活性分子并研究其作用机制是衰老药物学的研究重点和热点。前期研究发现天然产物多球壳菌素(一种神经鞘脂合成特异性抑制剂)能够延长模式生物芽殖酵母的寿命,而裂殖酵母在进化上更接近哺乳动物,且在形态和遗传上与芽殖酵母有显著差异的另一种模式生物,本研究考察了多球壳菌素对裂殖酵母寿命的影响,并进一步研究了其调控细胞寿命的相关机制。结果显示,多球壳菌素延长裂殖酵母寿命具有保守性,其延长细胞寿命的机制包括:增强细胞压力抗性、促进糖原和海藻糖的积累、降低胞内活性氧的水平,且发现多球壳菌素介导的寿命延长依赖于压力应答类蛋白激酶Sty1。综上,多球壳菌素是一种潜在的抗衰老药物分子,后期有望开发它用于延缓哺乳动物细胞(包括人类)衰老及预防和治疗衰老相关疾病。     

秀丽隐杆线虫模型在抗衰老研究中的应用

随着人口老龄化问题的凸显,衰老相关的研究越来越被重视。秀丽隐杆线虫（Caenorhabditis elegans）是抗衰老研究领域中非常重要的生物模型,具有生命周期短、易于培养和观察等优点,但与其他哺乳动物模型相比仍有一些局限性,如DNA甲基化的缺乏等。本文主要综述了秀丽隐杆线虫模型在抗衰老研究和药物筛选中的应用,包括抗衰老药物对线虫寿命和抗性的测定与评估、药物筛选以及健康衰老研究中的应用,并概括了该模型的优势和局限性,为秀丽隐杆线虫模型在抗衰老研究中的应用提供理论依据。     

中药补骨脂中黄酮类榛仁球蛋白(Corylin)具有延长小鼠寿命的特性CSCD

抗衰老药物既能促进人体健康衰老,又能用于老年相关疾病的治疗。在过去的20年中,老龄化研究一直是一个活跃的研究领域。有研究表明,TOR和SIRT1在寿命中发挥调节作用。TOR信号减少有助于延长寿命,但由于候选物种类的不足和筛选方法的局限,只有少数化合物被成功鉴定具有延长寿命的功效。     

综述: 秀丽线虫胰岛素类生长因子和雷帕霉素受体信号通路对衰老的调节作用

衰老表现为随着时间推移而带来的功能上的衰退和死亡率的上升.利用模式生物,研究人员已经证明,衰老受高度保守的信号通路所调控,而且遗传与环境因素的改变可以显著延长寿命并延缓功能上的衰退.作为一种模式生物,秀丽线虫由于其遗传操作的简单性以及基因组的高度保守性,已被广泛应用于现代生物学研究中.许多关于衰老的分子机理最初是在秀丽线虫中被阐明的.本文总结了秀丽线虫中高度保守的胰岛素类生长因子(IGF-1)和雷帕霉素受体(TOR)这两条信号通路调控衰老的研究进展,并对未来的研究方向展开了评述.     

秀丽线虫胰岛素类生长因子和雷帕霉素受体信号通路对衰老的调节作用

衰老表现为随着时间推移而带来的功能上的衰退和死亡率的上升.利用模式生物,研究人员已经证明,衰老受高度保守的信号通路所调控,而且遗传与环境因素的改变可以显著延长寿命并延缓功能上的衰退.作为一种模式生物,秀丽线虫由于其遗传操作的简单性以及基因组的高度保守性,已被广泛应用于现代生物学研究中.许多关于衰老的分子机理最初是在秀丽线虫中被阐明的.本文总结了秀丽线虫中高度保守的胰岛素类生长因子(IGF-1)和雷帕霉素受体(TOR)这两条信号通路调控衰老的研究进展,并对未来的研究方向展开了评述.     

模式生物秀丽隐杆线虫在肠道菌群研究中的应用

肠道菌群是人体的重要组成部分,在物质代谢、免疫应答等方面起着重要作用,目前对其组成和功能研究已成为热点。模式生物秀丽隐杆线虫因其结构简单、生活周期短、便于制备无菌个体等特性,在肠道菌群与机体共生关系及功能研究方面受到广泛应用。现就秀丽线虫在肠道菌群功能研究方面的应用进行综述。     

必需氨基酸延缓秀丽隐杆线虫衰老的研究

利用模式生物秀丽隐杆线虫,考察8种人体必需氨基酸对衰老的影响。首先建立秀丽隐杆线虫寿命模型,以雷帕霉素为阳性对照药,分别考察8种必需氨基酸对线虫生存时间的影响。再用筛选出的氨基酸处理线虫21d,通过秀丽隐杆线虫-绿脓杆菌感染模型,考察氨基酸对线虫的抗感染能力的影响,利用实时荧光定量Real-Time RT-PCR方法检测氨基酸处理线虫后DAF-16/FOXO下游基因和免疫相关基因的表达水平。结果表明8种必需氨基酸中苏氨酸和异亮氨酸既能延长野生型线虫的寿命又能延长daf-16突变型线虫的寿命,同时还能增强秀丽隐杆线虫抗绿脓杆菌感染的能力,并提高免疫相关基因lys-7、clec-67的表达水平,而DAF-16/FOXO下游基因表达没有明显变化。因此苏氨酸和异亮氨酸能延长线虫寿命、提高抗感染能力,且对线虫寿命的延长作用不完全依赖于DAF-16/FOXO转录因子。     

细菌与秀丽隐杆线虫之间互作关系的研究进展

秀丽隐杆线虫(Caenorhabditis elegans)以其个体小、易培养、生活周期短等优势成为生物发育、衰老、神经及免疫相关机制研究的模式生物.它在实验室培养时主要靠饲喂大肠杆菌OP50,有报道,细菌及其代谢物对线虫的代谢、行为和寿命有至关重要的影响.因此,作为一个遗传模型,秀丽隐杆线虫可以帮助研究微生物与宿主相...     

Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans

The beneficial effects of polyphenol compounds in fruits and vegetables are mainly extrapolated from in vitro studies or short-term dietary supplementation studies. Due to cost and duration, relatively little is known about whether dietary polyphenols are beneficial in whole animals, particularly with respect to aging. To address this question, we examined the effects of blueberry polyphenols on lifespan and aging of the nematode, Caenorhabditis elegans, a useful organism for such a study. We report that a complex mixture of blueberry polyphenols increased lifespan and slowed aging-related declines in C. elegans. We also found that these benefits did not just reflect antioxidant activity in these compounds. For instance, blueberry treatment increased survival during acute heat stress, but was not protective against acute oxidative stress. The blueberry extract consists of three major fractions that all contain antioxidant activity. However, only one fraction, enriched in proanthocyanidin compounds, increased C. elegans lifespan and thermotolerance. To further determine how polyphenols prolonged C. elegans lifespan, we analyzed the genetic requirements for these effects. Prolonged lifespan from this treatment required the presence of a CaMKII pathway that mediates osmotic stress resistance, though not other pathways that affect stress resistance and longevity. In conclusion, polyphenolic compounds in blueberries had robust and reproducible benefits during aging that were separable from antioxidant effects.     

Some highlights of research on aging with invertebrates, 2009

This annual review focuses on invertebrate model organisms, which shed light on new mechanisms in aging and provide excellent systems for both genome-wide and in-depth analysis. This year, protein interaction networks have been used in a new bioinformatic approach to identify novel genes that extend replicative lifespan in yeast. In an extended approach, using a new, human protein interaction network, information from the invertebrates was used to identify new, candidate genes for lifespan extension and their orthologues were validated in the nematode Caenorhabditis elegans . Chemosensation of diffusible substances from bacteria has been shown to limit lifespan in C. elegans , while a systematic study of the different methods used to implement dietary restriction in the worm has shown that they involve mechanisms that are partially distinct and partially overlapping, providing important clarification for addressing whether or not they are conserved in other organisms. A new theoretical model for the evolution of rejuvenating cell division has shown that asymmetrical division for either cell size or for damaged cell constituents results in increased fitness for most realistic levels of cellular protein damage. Work on aging-related disease has both refined our understanding of the mechanisms underlying one route to the development of Parkinson's disease and has revealed that in worms, as in mice, dietary restriction is protective against cellular proteotoxicity. Two systematic studies genetically manipulating the superoxide dismutases of C. elegans support the idea that damage from superoxide plays little or no role in aging in this organism, and have prompted discussion of other kinds of damage and other kinds of mechanisms for producing aging-related decline in function.     

Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans

Resveratrol and SRT1720 have been shown to act as sirtuin activators that may ameliorate type 2 diabetes and metabolic diseases in mice. Moreover, resveratrol extends lifespan in model organisms like C. elegans, N. FURZERI, and possibly D. melanogaster. The aim of the study was to test whether pharmacological concentrations of resveratrol and SRT1720 are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. ELEGANS roundworms were maintained on agar plates and fed E. COLI strain OP50 bacteria. Resveratrol (5 micromolar, 500 nanomolar) or SRT1720 (1 micromolar, 100 nanomolar) was applied to the agar to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extends C. elegans lifespan by 3.6% (mean lifespan) and 3.4% (maximum lifespan). By unexpected contrast, SRT1720, which was previously proposed to be several hundred times more active than resveratrol, did not extend lifespan at none of the concentrations tested. Thus, in the model organisms C. elegans, resveratrol is capable of promoting longevity at a concentration that pharmacologically relevant and 20 times lower than previously published doses. The sirtuin activator SRT1720 did not extend lifespan, suggesting that in C. elegans, some relevant effects of resveratrol cannot be mimicked by SRT1720.     

Valproic acid extends Caenorhabditis elegans lifespan

Aging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging. Caenorhabditis elegans is a valuable model for studies of animal aging, and the analysis of drugs that extend the lifespan of this animal can elucidate mechanisms of aging and might lead to treatments for age-related disease. By testing drugs that are Food and Drug Administration approved for human use, we discovered that the mood stabilizer and anticonvulsant valproic acid (VA) extended C. elegans lifespan. VA also delayed age-related declines of body movement, indicating that VA delays aging. Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans. A structure-activity analysis demonstrated that the related compound valpromide also extends lifespan. Valproic acid treatment may modulate the insulin/IGF-1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF-16 nuclear localization. To investigate the mechanism of action of VA in delaying aging, we analyzed the effects of combining VA with other compounds that extend the lifespan of C. elegans. Combined treatment of animals with VA and the heterocyclic anticonvulsant trimethadione caused a lifespan extension that was significantly greater than treatment with either of these drugs alone. These data suggest that the mechanism of action of VA is distinct from that of trimethadione, and demonstrate that lifespan-extending drugs can be combined to produce additive effects.     

No increase in lifespan in Caenorhabditis elegans upon treatment with the superoxide dismutase mimetic EUK-8

The superoxide dismutase mimetic EUK-8 has been reported to extend lifespan in the nematode Caenorhabditis elegans. However, in five trials administering EUK-8 in liquid culture with E. coli, and two trials using defined liquid medium, we observed no increase in C. elegans lifespan. Instead we saw a dose-dependent reduction of lifespan and fertility. We conclude that extension of C. elegans lifespan by EUK-8 may only occur under very particular culture conditions.     

A steroid hormone that extends the lifespan of Caenorhabditis elegans

Removing the germline of Caenorhabditis elegans extends lifespan. This lifespan extension requires the nuclear receptor DAF-12 and the cytochrome P450 DAF-9, suggesting that a lipophilic hormone is involved. Here we show that C. elegans contains several hormonal steroids that are also present in humans, including pregnenolone (3beta-hydroxy-pregn-5-en-20-one; PREG) and other pregnane and androstane derivatives. We find that PREG can extend the lifespan of C. elegans. Moreover, PREG levels rise when the germline is removed in a daf-9-dependent fashion. PREG extends the lifespan of germline-defective daf-9 mutants dramatically, but has no effect on daf-12 mutants. Thus, germline removal may extend lifespan, at least in part, by stimulating the synthesis of PREG.