淫羊藿苷延长秀丽线虫寿命与机制

目的探讨淫羊藿苷（Icariin,Ica）对秀丽线虫寿命的干预效果与机制,为筛选延缓衰老、延长寿命的药物提供实验依据。方法将秀丽线虫分为空白对照组、Ica5mg／L、10mg／L、15mg／L、20mg／L各剂量干预实验组,观察在Ica不同梯度剂量作用下秀丽线虫寿命的变化,以明确Ica作用的最佳剂量。接着设立秀丽线虫空白对照组和Ica（15mg／L）干预组,评价Ica对秀丽线虫平均寿命、生殖能力的干预效果;同时进行急性热应激和急性氧化应激实验,观察应激时线虫的平均生存时间,探讨Ica延长线虫寿命的机制。结果15mg／L的Ica是延长秀丽线虫寿命的最佳剂量。Ica组线虫的平均寿命明显长于空白对照组[（31．87±4．46）d vs．（20．13±2．81）d]（P〈0．01）;Ica组线虫生殖高峰期子代数目比空白对照组显著增加（151±21．13VS．122±17．09,P〈O．01）;急性热应激实验和急性氧化应激实验发现Ica组线虫平均生存时间均明显长于空白对照组[（9．53±1．34）hVS．（5．97±0．84）h,（8．34±1．17）hvs.（5．77±O．81）h]（P〈0．01）。结论淫羊藿苷能延长秀丽线虫的寿命,其机制可能与淫羊藿苷提高线虫的应激能力有关。     

应用秀丽隐杆线虫评估重金属生物毒性效应研究

目的 目的 应用秀丽隐杆线虫评估重金属生物毒性效应。方法 方法 将L4期秀丽隐杆线虫暴露于低浓度的CdCl2、 CrCl3、 As2O3、 PbCl2和HgCl2溶液及M9缓冲液 （对照组） 中72 h, 评价不同浓度重金属暴露对线虫生存时间和生殖毒性的影 响。 结果 结果 2.5、 10 μmol/L的HgCl2 和PbCl2、 10 μmol/L CdCl2、 50 μmol/L CrCl3染毒线虫72 h后, 与对照组相比, 线虫平均 寿命均缩短, 平均寿命及生存曲线差异均有统计学意义 （P均< 0.05）。L4期线虫分别在2.5、 50、 100 μmol/L上述重金属 溶液中暴露72 h, 世代时间延长、 后代数目减少, 与对照组比较差异均有统计学意义 （P均 < 0.01）。在低浓度时, Hg生殖 毒性较Pb、 Cd、 Cr大, As毒性较弱。结论 结论 重金属暴露对秀丽隐杆线虫寿命有一定影响, 可致子代生殖能力下降。     

5种重金属暴露对秀丽线虫生物毒性效应的Meta回归分析

目的 目的 评价5种重金属暴露对秀丽线虫的生物毒性效应。方法 方法 以秀丽线虫、 重金属等为关键词检索 PubMed、 Web of Science、 EBSCO、 中国知网、 万方等国内外数据库, 检索时间为2004?01-2014?12, 按照文献纳入和排除标 准筛选关于镉 （Cd）、 汞 （Hg）、 铅 （Pb）、 砷 （As）、 铬 （Cr） 及铜 （Cu） 暴露对秀丽线虫毒性效应的文献。提取文献中相关数据, 以秀丽线虫的毒性指标终点为因变量, 不同金属种类、 暴露浓度、 暴露时间等为自变量, 采用Meta回归分析比较5种重金 属暴露对秀丽线虫的生物毒性效应。结果 结果 根据文献纳入和排除标准, 最终筛选出有关Cu暴露对秀丽线虫生物毒性的 文献10 篇、 有关Cr的文献12篇、 有关Pb的文献12篇、 有关Cd的文献10 篇、 有关As的文献3 篇、 有关Hg的文献14 篇。 Meta回归分析显示, 以Cu为参照, 5种重金属对秀丽线虫致死率排序为Hg > Pb > Cr > Cd > As, 回归模型校正决定系数 为0.600 8; 基于发育影响的体长指标、 基于生殖毒性的世代时间指标、 基于神经毒性的身体弯曲度指标和头部摆动频率 指标的毒性效应排序均为Hg > Pb > Cr > Cd, 回归模型校正决定系数分别为0.888 4、 0.538 6、 0.698 6和0.747 1; 根据LC50 指标, 各重金属对线虫毒性效应排序为Hg > Pb > Cr > Cd > As。敏感性分析显示, Meta回归分析结果较为稳定。结论 结论 Hg、 Pb对秀丽线虫的生物毒性效应强于Cr、 Cd和As。     

表观遗传年龄与衰老和心血管疾病的研究进展

衰老作为心血管疾病的重要风险因素,其相关致病机制的研究一直受到广泛重视,寻找能准确地评估和预测人体衰老程度的标志物是生物医学领域的研究热点。表观遗传调控被证实参与了多种心血管疾病的致病机制。近年来,发现利用人体DNA甲基化图谱构建的DNA甲基化年龄,也叫表观遗传时钟,可准确地评估个体生物年龄并评估组织器官功能衰退程度。表观遗传年龄被证实与衰老相关心血管疾病风险密切相关,有望成为新的临床生物标志物用于心血管疾病患者的个体化治疗。现就表观遗传年龄的发展、与衰老和心血管疾病的关系、研究现状及应用做详细阐述。     

自噬调控衰老的研究进展

随着机体老化,组织器官可发生不可逆退行性改变,这些变化与疾病和死亡密切相关。自噬是细胞内一种重要的分解代谢过程,在维持细胞稳态和促进长寿中起重要作用,机体衰老后,其自噬调节能力也随之下降。本文综述了自噬与衰老相关疾病的关系,明确自噬调控衰老的相关分子机制可能为治疗衰老相关疾病提供新的靶点。     

环境酸碱度对秀丽隐杆线虫生长发育及毒性试验的影响

目的  探讨不同的pH值环境对培养秀丽隐杆线虫及其在毒性评价试验中的影响。 方法  通过监测秀丽隐杆线虫培养环境中pH值随时间的变化及设置不同的pH值环境,观察pH值环境变化对秀丽隐杆线虫生长发育的影响。结果  在酸性环境中培养,线虫繁殖率低,在中性环境中繁殖良好,在碱性环境中,几乎未见繁殖现象。线虫在中性环境中培养时,随时间延长pH值升高。染毒试验中毒液pH值酸碱性环境不同,线虫致死率差异有统计学意义（χ2=31.344,Ｐ<0.001）。结论  不同pH值培养环境影响秀丽隐杆线虫的生长发育,在培养过程中应及时调整pH值环境和更换新培养皿,毒性评价试验时应注意环境pH值对线虫生长发育的影响。     

衰老机制研究进展

<正>衰老与增龄相关的老年慢性病(如心脑血管疾病,中枢神经病,风湿免疫病、退行性骨关节炎)的发生、发展密切相关。因此,随着人口老龄化的加剧,深入探索衰老机制,不但有助于机体抗衰老、保健的研究与实践及延长寿命,而且对于防治与增龄相关的老年病具有重大意义。随着包括自由基理论、长寿基因、端粒酶理论及表观遗传学等领域研究的进展,科学家们在衰老的内在和外在的机制上有了更深入的认识。本文对近年来有关衰老机制研究中具有代表性的     

哮喘遗传与基因调控

哮喘是一种多基因遗传病,受多因素调控。本文就哮喘与遗传的关系、遗传与气道高反应性、IgE的免疫遗传控制、哮喘与炎症介质基因调控等作一综述。     

表观遗传调控在动脉粥样硬化中的研究进展

表观遗传是在基因组DNA序列不发生改变的条件下,基因表达发生了可遗传性改变.发生动脉粥样硬化时,炎性细胞因子、氧化低密度脂蛋白和内膜下的胆固醇晶体等刺激巨噬细胞,诱导其发生表观遗传学改变,从而导致巨噬细胞无法正常转录.靶向干预泡沫细胞的表观遗传改变可能是抑制巨噬细胞表型转变及降低粥样斑块形成速度的有效治疗策略.组蛋白修...     

Hormesis and aging in Caenorhabditis elegans

Hormesis has emerged as an important manipulation for the study of aging. Although hormesis is manifested in manifold combinations of stress and model organism, the mechanisms of hormesis are only partly understood. The increased stress resistance and extended survival caused by hormesis can be manipulated to further our understanding of the roles of intrinsic and induced stress resistance in aging. Genes of the dauer/insulin/insulin-like signaling (IIS) pathway have well-established roles in aging in Caenorhabditis elegans. Here, we discuss the role of some of those genes in the induced stress resistance and induced life extension attributable to hormesis. Mutations in three genes (daf-16, daf-18, and daf-12) block hormetically induced life extension. However, of these three, only daf-18 appears to be required for a full induction of thermotolerance induced by hormesis, illustrating possible separation of the genetic requirements for stress resistance and life extension. Mutations in three other genes of this pathway (daf-3, daf-5, and age-1) do not block induced life extension or induced thermotolerance; daf-5 mutants may be unusually sensitive to hormetic conditions.     

Neurosecretory control of aging in Caenorhabditis elegans

In the nematode Caenorhabditis elegans, an insulin receptor signaling pathway regulates adult life span and developmental arrest at the dauer larval stage. Here we show that the unc-64 and unc-31 genes also function in this pathway. These two genes are involved in mediating Ca2+-regulated secretion. Mutations in unc-64 and unc-31 increase adult life span and cause constitutive dauer formation. Both phenotypes are suppressed by mutations in daf-16, which also suppresses other mutations in this pathway. We present evidence that the site of action of unc-64 is neuronal, suggesting that a neurosecretory signal regulates life span and dauer formation.     

Advantages and disadvantages of Caenorhabditis elegans for aging research

The nematode Caenorhabditis elegans has been the organism of choice for most aging research, especially genetic approaches to aging. More than 70 longevity genes have been identified, with more to come, and these genes have been the subjects of intense study. I identify the major reasons for this and discuss limitations of this organism for future progress in research on aging.     

Genetic analysis of life-span in Caenorhabditis elegans.

Crosses between Bristol and Bergerac strains of the self-fertilizing hermaphroditic nematode Caenorhabditis elegans do not show the heterosis effects for life-span that complicate analysis of interstrain crosses with Drosophila or mice. Instead they yield F1 progeny with life-spans similar to those of the parent strains. By analysis of life-span variation among progeny F2 populations from such crosses and by two independent analyses of life-spans among recombinant inbred lines derived from F2 individuals by 18 rounds of self-fertilization, we estimate that the heritability of life-span in C. elegans is between 20% and 50%. Recombinant inbred lines show a range in mean life-spans of 10 days to 31 days compared to life-spans of about 18 days for each of the two parental strains. We conclude that life-span variation in C. elegans has a substantial genetic component and that this organism offers promising opportunities for selective breeding of longer-lived strains and genetic analysis of senescence.     

Genetic dissection of late-life fertility in Caenorhabditis elegans

The large post-reproductive life span reported for the free-living hermaphroditic nematode, Caenorhabditis elegans, which lives for about 10 days after its 5-day period of self-reproduction, seems at odds with evolutionary theory. Species with long post-reproductive life spans such as mammals are sometimes explained by a need for parental care or transfer of information. This does not seem a suitable explanation for C elegans. Previous reports have shown that C elegans can regain fertility when mated after the self-fertile period but did not report the functional limits. Here, we report the functional life span of the C elegans germ line when mating with males. We show that C elegans can regain fertility late in life (significantly later than in previous reports) and that the end of this period corresponds quite well to its 3-week total life span. Genetic analysis reveals that late-life fertility is controlled by conserved pathways involved with aging and dietary restriction.     

Identifying factors that promote functional aging in Caenorhabditis elegans

A major feature of aging is a reduction in muscle strength from sarcopenia, the loss of muscle mass. Sarcopenia impairs physical ability, reduces quality of life and increases the risk of fall and injury. Since aging is a process of stochastic decline, there may be many factors that impinge on the progression of sarcopenia. Possible factors that may promote muscle decline are contraction-related injury and oxidative stress. However, relatively little is understood about the cellular pathways affecting muscle aging, in part because lifespan studies are difficult to conduct in species with large muscles, such as rodents and primates. For this reason, shorter-lived invertebrate models of aging may be more useful for unraveling causes of sarcopenia and functional declines during aging. Recent studies have examined both physiological and genetic factors that affect aging-related declines in Caenorhabditis elegans nematodes. In C. elegans, aging leads to significant functional declines that correlate with muscle deterioration, similar to those documented for longer-lived vertebrates. This article will examine the current research into aging-related functional declines in this species, focusing on recent studies of locomotory and feeding decline during aging in the nematode, C. elegans.     

Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans

The identification and analysis of compounds that delay aging and extend lifespan is an important aspect of gerontology research; these studies can test theories of aging, lead to the discovery of endogenous systems that influence aging, and establish the foundation for treatments that might delay normal human aging. Here we review studies using the nematode Caenorhabditis elegans to identify and characterize compounds that delay aging and extend lifespan. These studies are considered in four groups: (1) Studies that address the free-radical theory of aging by analyzing candidate compounds with antioxidant activities including vitamin E, tocotrienols, coenzyme Q, and Eukarion-8/134. (2) Studies that analyze plant extracts (blueberry and Ginko biloba) that contain a mixture of compounds. (3) Studies of resveratrol, which was identified in a screen for compounds that affect the activity of the Sir2 protein that influences lifespan. (4) Studies based on screening compound libraries using C. elegans aging as a bioassay, which led to the identification of the anticonvulsant medicines ethosuximide and trimethadione. There has been exciting progress in the analysis of compounds that influence C. elegans aging, and important challenges and opportunities remain in determining the mechanisms of action of these compounds and the relevance of these observations to aging of other animals.