滋补肝肾、行气活血类中药延缓线虫衰老的作用及分子机制研究
|
摘要
研究背景
21世纪是人口老龄化时代,人口老龄化和增长过快给社会经济、文化、教育、医疗、保健等都带来了巨大的压力和挑战。因此,探索衰老的内涵,寻找有效的延缓衰老的方式,是当前重要且紧迫的任务。衰老研究主要包括衰老机制研究和延缓衰老药物研究。迄今为止,解释衰老机理的学说多达200余种,其中包括：自由基损伤说、神经内分泌紊乱说、代谢学说、线粒体损伤学说、限食理论等。然而归根结底,上述学说都受基因表达调控的影响,任何一种衰老学说都有与之相对应的基因表达改变,可以在基因水平将各种学说统一起来研究衰老及药物对衰老的影响。
中医药学在长期实践中形成了独特的衰老理论,并在此基础上发现了许多具有延年益寿功效的中药,具有很大的研究价值。中医肝、肾与衰老关系密切,肾虚是衰老之本,肝虚是衰老之助。二至丸为临床常用的滋补肝肾的名方,现代研究证实其确有延缓衰老作用,需要进一步探讨其分子机制。“气滞血瘀”也是人体衰老的主要机制之一。行气活血方剂能改善微循环、提高免疫、提高应激能力等,从而延缓衰老。川芎为活血行气之要药,临床应用广泛,具有改善微循环、调节免疫等多种药理作用,显示了良好的延缓衰老作用,值得进行深入研究。
秀丽隐杆线虫因其寿命周期短、廉价易培养、子代数目多、细胞数目简单、遗传背景清楚等优点已成为良好的衰老研究的实验动物。
本课题以线虫为研究对象,首先对传统中医或临床实践认为可以延缓衰老的30多种中药及其有效成份进行寿命实验的筛选研究,筛选出能延寿的及其最佳延寿浓度(以滋补肝肾中药—二至丸、行气活血中药—川芎为代表),并进一步观察上述药物对线虫繁殖力和急性热应激能力的影响。在此基础上,采用realtime RT-PCR技术检测分析上述中药对不同衰老学说涉及的衰老／长寿基因表达的影响,探讨并比较分析两类中药延缓衰老作用在分子机制上的异同。
实验研究
1延缓线虫衰老中药筛选
建立了中药及其有效成分直接添加入线虫培养基的中药干预线虫培养方法及寿命实验筛选的方法,并对30多种中药及其有效组分进行了延长线虫寿命作用的筛选,发现7种药物具有延寿或延寿趋势。以滋补肝肾中药复方—二至丸、行气活血中药—川芎提取物为代表。
2二至丸(EZW)对线虫衰老的影响及分子机制研究
发现二至丸水提液具有较好的延长线虫寿命的作用,以500mg／L浓度组为最佳,线虫平均寿命延长10.6%(P<0.01),最大寿命延长16.2%(P<0.01)；二至丸水提液能一定程度的提高线虫的急性热应激能力,不影响其繁殖力。采用实时荧光定量RT-PCR方法发现二至丸延缓衰老作用与调控IIS信号通路、神经内分泌、生物钟等多个途径的基因表达有关。
3川芎提取物(CXE)对线虫衰老的影响及分子机制研究
发现川芎提取物具有较好的延长线虫寿命的作用,以25mg／L浓度组为最佳,线虫平均寿命延长29.9%(P<0.01),最大寿命延长9.4%(P<0.01)；川芎提取物能一定程度的提高线虫的急性热应激能力,不影响其繁殖力。采用实时荧光定量RT-PCR方法研究其延缓衰老的分子机制,发现在衰老自然进程中,线虫体内与衰老关系密切的IIS信号通路和限食通路的基因表达发生变化——衰老基因的表达量开始增加,而长寿基因的表达量开始减少。川芎提取物通过调控IIS信号、抑制脂肪积累、提高线粒体活性等与能量代谢有关的基因和抗氧化应激等多个生理生化途径共同影响线虫的生理机能,发挥延缓衰老的功效。
总结
本研究采用适合大规模药物筛选和机制研究的模式生物线虫对30多种中药及其有效成分进行了寿命实验筛选,共筛选出7种具有延寿或延寿趋势的药物,以滋补肝肾中药复方—二至丸和行气活血中药川芎为代表。
二至丸和川芎水提液均能延长线虫寿命、提高应激能力,不影响其繁殖力。两药延缓衰老的分子机制上存在异同点,相同点是上述两药物均能调控IIS信号通路,促进“长寿基因”表达,抑制“衰老基因”表达；不同点在于除IIS外,二至丸还调控神经内分泌、生物钟等途径,而川芎提取物主要调控与能量代谢有关的基因,如限食通路、线粒体活性、脂肪积累等。
因此,有延缓衰老作用的不同中药具有不同的分子靶点和作用机制,能否利用这一特点从分子靶点入手在中医理论指导下进行各类中药的药效及中药的组分再配伍研究有必要在今后的工作中进行进一步探索。
本研究将多种衰老学说统一到基因水平进行研究,更有助于观察各衰老理论的相互关系和调控网络,有利于寻找真正有效的衰老功能基因群,更好地为延缓衰老药物的机制研究和新药开发服务。
The 21st century is the era of aging population, aging and overgrowth of the population bring great challenges to social economy, culture,education and medical care.Therefore,it is an important ergent task to explore the mechanisms of aging and find out the effective way to delay aging.The mechanisms of aging are important contents of aging research. So far, there are more than 200 theories about aging, including damage of free radicals, disorder of neuroendocrine system, disorder of metabolism, damage of mitochondria, dietary restriction, etc. But all in all, the theories above are all regulated by gene expression. There are always some related gene expression changes corresponding to any kind of the aging theories. So, the theories could be integrated at the genetic level to investigate the aging mechanisms and the effects of medicine on it.
During the long-term clinical practices of traditional Chinese medicine (TCM), many unique aging theories have been formed, a lot of TCM formulas that could retard aging effectively have been found as well with great value for research and application. In TCM, kidney and liver have close relationships with aging that kidney deficiency is the foundation of aging while liver deficiency is the aid of it. Erzhi Wan is a famous formula with founction of nourishing kidney and liver(NKL), which has been widely used in clinical practices.Since its anti-aging effects has been proved, it is necessary to explore the underlying molecular mechanisms. Qi stagnation and blood stasis(QSBS) is another important TCM theory of aging. The formulas with founctions of promoting Qi and activating Blood (PQAB)could delay aging through improving microcirculation and immunity, strengthening the ability of stess resistence. Chuanxiong is a typical TCM with functions mentioned above that deserves further research.
Caenorhabditis elegans(C.elegans) has been an excellent organism for aging research with good characters of short lifespan, cheap and easy to culture, huge amounts of offspring, small numbers of cells, well-understood genetic background, ect.
In the study, we chose C.elegans as a organism model to screen the medicines that could prolong lifespan of the animal from more than 30 kinds of TCMs. Among them, Erzhi Wan and Chuanxiong were the typical ones.The effects of them on reproductivity and acute heat-resisting ability of the nematodes were also investigated. In addition, we used realtime RT-PCR to explore the different underlying molecular mechanisms between these two TCMs.
The method of culturing C.elegans with TCMs was established that the water extract of TCMs could be added directly to the mediums; By lifespan assay,7 of 30 TCMs were screened out for lifespan-prolonging effects on C. elegans, Erzhi Wan and Chuanxiong are the typical ones.
We found that the water extract of Erzhi Wan could prolong lifespan of C.elegans effectively and the optimal concentration is 500mg/L. The mean lifespan could be extended by 10.6% (P<0.01), and the maximum lifespan was extended by 16.2% (P <0.01). Furthermore, the acute heat-resisting ability of the animal was increased to a certain extent while the reproductivity remained unchanged. By using realtime RT-PCR, we found that the anti-aging effects of Erzhi Wan pertain to the regulation of genes expression in IIS pathway,neuroendocrine and clock genes,ect.
We found that the water extract of CXE could prolong lifespan of C.elegans effectively and the optimal concentration is 25mg/L. The mean lifespan could be extended by 29.9% (P<0.01), and the maximum lifespan was extended by 9.4% (P< 0.01). Furthermore, the acute heat-resisting ability of the animal was increased to a certain extent while the reproductivity remained unchanged. By using realtime RT-PCR, we found that:①In the progress of aging, the expression of aging genes in IIS and dietary restriction pathway increased, while the expression of longevity genes decreased;②CXE entended the lifespan through regulating genes expression of IIS, inhibiting TOR signal, improving antioxidation, stress resisting and mitochondria activity, which contributed to affecting the physiology of C.elegans.
In the study, we used a model organism-C.elegans, which was suitable for large-scale medicine screening and mechanism research, to screen medicines that could delay senility effectively. Among more than 30 kinds of TCMs,7 TCMs were screened out for medicines that could prolong lifespan effectively, Erzhi Wan (NKL) and Chuanxiong (PQAB) were the typical ones.
Both Chuanxiong and Erzhi Wan could extend the lifespan and improve the heat-resisting ability of C.elegans with no reduction of reproductivity. But there were similarities and differences of molecular mechanisms between these two TCMs. The similarity was that both of them have relationships with IIS, the longevity genes of the pathway were upregulated while aging genes were downregulated.The differences were:besides IIS, Erzhi Wan affected aging mainly through regulating neuroendocrine genes and clock genes while Chuanxiong mostly affected genes of energe metabolisms, such as dietary restriction, mitochondrial activity and fat storage, etc.
Consequently, different anti-aging TCM has different molecular mechanisms.We wondered whether this character could be used to study the efficacy and component compatability of TCMs proceeded with molecular targets in the future.
In this study, we integrated several aging theories at the genetic level, which contributes to understand the relationship and regulating network among them more easily, helps to seek for the real function genes affecting aging. We considered the methods would bring great benefits for mechanism research and development of new medicine.
21世纪是人口老龄化时代,人口老龄化和增长过快给社会经济、文化、教育、医疗、保健等都带来了巨大的压力和挑战。因此,探索衰老的内涵,寻找有效的延缓衰老的方式,是当前重要且紧迫的任务。衰老研究主要包括衰老机制研究和延缓衰老药物研究。迄今为止,解释衰老机理的学说多达200余种,其中包括：自由基损伤说、神经内分泌紊乱说、代谢学说、线粒体损伤学说、限食理论等。然而归根结底,上述学说都受基因表达调控的影响,任何一种衰老学说都有与之相对应的基因表达改变,可以在基因水平将各种学说统一起来研究衰老及药物对衰老的影响。
中医药学在长期实践中形成了独特的衰老理论,并在此基础上发现了许多具有延年益寿功效的中药,具有很大的研究价值。中医肝、肾与衰老关系密切,肾虚是衰老之本,肝虚是衰老之助。二至丸为临床常用的滋补肝肾的名方,现代研究证实其确有延缓衰老作用,需要进一步探讨其分子机制。“气滞血瘀”也是人体衰老的主要机制之一。行气活血方剂能改善微循环、提高免疫、提高应激能力等,从而延缓衰老。川芎为活血行气之要药,临床应用广泛,具有改善微循环、调节免疫等多种药理作用,显示了良好的延缓衰老作用,值得进行深入研究。
秀丽隐杆线虫因其寿命周期短、廉价易培养、子代数目多、细胞数目简单、遗传背景清楚等优点已成为良好的衰老研究的实验动物。
本课题以线虫为研究对象,首先对传统中医或临床实践认为可以延缓衰老的30多种中药及其有效成份进行寿命实验的筛选研究,筛选出能延寿的及其最佳延寿浓度(以滋补肝肾中药—二至丸、行气活血中药—川芎为代表),并进一步观察上述药物对线虫繁殖力和急性热应激能力的影响。在此基础上,采用realtime RT-PCR技术检测分析上述中药对不同衰老学说涉及的衰老／长寿基因表达的影响,探讨并比较分析两类中药延缓衰老作用在分子机制上的异同。
实验研究
1延缓线虫衰老中药筛选
建立了中药及其有效成分直接添加入线虫培养基的中药干预线虫培养方法及寿命实验筛选的方法,并对30多种中药及其有效组分进行了延长线虫寿命作用的筛选,发现7种药物具有延寿或延寿趋势。以滋补肝肾中药复方—二至丸、行气活血中药—川芎提取物为代表。
2二至丸(EZW)对线虫衰老的影响及分子机制研究
发现二至丸水提液具有较好的延长线虫寿命的作用,以500mg／L浓度组为最佳,线虫平均寿命延长10.6%(P<0.01),最大寿命延长16.2%(P<0.01)；二至丸水提液能一定程度的提高线虫的急性热应激能力,不影响其繁殖力。采用实时荧光定量RT-PCR方法发现二至丸延缓衰老作用与调控IIS信号通路、神经内分泌、生物钟等多个途径的基因表达有关。
3川芎提取物(CXE)对线虫衰老的影响及分子机制研究
发现川芎提取物具有较好的延长线虫寿命的作用,以25mg／L浓度组为最佳,线虫平均寿命延长29.9%(P<0.01),最大寿命延长9.4%(P<0.01)；川芎提取物能一定程度的提高线虫的急性热应激能力,不影响其繁殖力。采用实时荧光定量RT-PCR方法研究其延缓衰老的分子机制,发现在衰老自然进程中,线虫体内与衰老关系密切的IIS信号通路和限食通路的基因表达发生变化——衰老基因的表达量开始增加,而长寿基因的表达量开始减少。川芎提取物通过调控IIS信号、抑制脂肪积累、提高线粒体活性等与能量代谢有关的基因和抗氧化应激等多个生理生化途径共同影响线虫的生理机能,发挥延缓衰老的功效。
总结
本研究采用适合大规模药物筛选和机制研究的模式生物线虫对30多种中药及其有效成分进行了寿命实验筛选,共筛选出7种具有延寿或延寿趋势的药物,以滋补肝肾中药复方—二至丸和行气活血中药川芎为代表。
二至丸和川芎水提液均能延长线虫寿命、提高应激能力,不影响其繁殖力。两药延缓衰老的分子机制上存在异同点,相同点是上述两药物均能调控IIS信号通路,促进“长寿基因”表达,抑制“衰老基因”表达；不同点在于除IIS外,二至丸还调控神经内分泌、生物钟等途径,而川芎提取物主要调控与能量代谢有关的基因,如限食通路、线粒体活性、脂肪积累等。
因此,有延缓衰老作用的不同中药具有不同的分子靶点和作用机制,能否利用这一特点从分子靶点入手在中医理论指导下进行各类中药的药效及中药的组分再配伍研究有必要在今后的工作中进行进一步探索。
本研究将多种衰老学说统一到基因水平进行研究,更有助于观察各衰老理论的相互关系和调控网络,有利于寻找真正有效的衰老功能基因群,更好地为延缓衰老药物的机制研究和新药开发服务。
The 21st century is the era of aging population, aging and overgrowth of the population bring great challenges to social economy, culture,education and medical care.Therefore,it is an important ergent task to explore the mechanisms of aging and find out the effective way to delay aging.The mechanisms of aging are important contents of aging research. So far, there are more than 200 theories about aging, including damage of free radicals, disorder of neuroendocrine system, disorder of metabolism, damage of mitochondria, dietary restriction, etc. But all in all, the theories above are all regulated by gene expression. There are always some related gene expression changes corresponding to any kind of the aging theories. So, the theories could be integrated at the genetic level to investigate the aging mechanisms and the effects of medicine on it.
During the long-term clinical practices of traditional Chinese medicine (TCM), many unique aging theories have been formed, a lot of TCM formulas that could retard aging effectively have been found as well with great value for research and application. In TCM, kidney and liver have close relationships with aging that kidney deficiency is the foundation of aging while liver deficiency is the aid of it. Erzhi Wan is a famous formula with founction of nourishing kidney and liver(NKL), which has been widely used in clinical practices.Since its anti-aging effects has been proved, it is necessary to explore the underlying molecular mechanisms. Qi stagnation and blood stasis(QSBS) is another important TCM theory of aging. The formulas with founctions of promoting Qi and activating Blood (PQAB)could delay aging through improving microcirculation and immunity, strengthening the ability of stess resistence. Chuanxiong is a typical TCM with functions mentioned above that deserves further research.
Caenorhabditis elegans(C.elegans) has been an excellent organism for aging research with good characters of short lifespan, cheap and easy to culture, huge amounts of offspring, small numbers of cells, well-understood genetic background, ect.
In the study, we chose C.elegans as a organism model to screen the medicines that could prolong lifespan of the animal from more than 30 kinds of TCMs. Among them, Erzhi Wan and Chuanxiong were the typical ones.The effects of them on reproductivity and acute heat-resisting ability of the nematodes were also investigated. In addition, we used realtime RT-PCR to explore the different underlying molecular mechanisms between these two TCMs.
The method of culturing C.elegans with TCMs was established that the water extract of TCMs could be added directly to the mediums; By lifespan assay,7 of 30 TCMs were screened out for lifespan-prolonging effects on C. elegans, Erzhi Wan and Chuanxiong are the typical ones.
We found that the water extract of Erzhi Wan could prolong lifespan of C.elegans effectively and the optimal concentration is 500mg/L. The mean lifespan could be extended by 10.6% (P<0.01), and the maximum lifespan was extended by 16.2% (P <0.01). Furthermore, the acute heat-resisting ability of the animal was increased to a certain extent while the reproductivity remained unchanged. By using realtime RT-PCR, we found that the anti-aging effects of Erzhi Wan pertain to the regulation of genes expression in IIS pathway,neuroendocrine and clock genes,ect.
We found that the water extract of CXE could prolong lifespan of C.elegans effectively and the optimal concentration is 25mg/L. The mean lifespan could be extended by 29.9% (P<0.01), and the maximum lifespan was extended by 9.4% (P< 0.01). Furthermore, the acute heat-resisting ability of the animal was increased to a certain extent while the reproductivity remained unchanged. By using realtime RT-PCR, we found that:①In the progress of aging, the expression of aging genes in IIS and dietary restriction pathway increased, while the expression of longevity genes decreased;②CXE entended the lifespan through regulating genes expression of IIS, inhibiting TOR signal, improving antioxidation, stress resisting and mitochondria activity, which contributed to affecting the physiology of C.elegans.
In the study, we used a model organism-C.elegans, which was suitable for large-scale medicine screening and mechanism research, to screen medicines that could delay senility effectively. Among more than 30 kinds of TCMs,7 TCMs were screened out for medicines that could prolong lifespan effectively, Erzhi Wan (NKL) and Chuanxiong (PQAB) were the typical ones.
Both Chuanxiong and Erzhi Wan could extend the lifespan and improve the heat-resisting ability of C.elegans with no reduction of reproductivity. But there were similarities and differences of molecular mechanisms between these two TCMs. The similarity was that both of them have relationships with IIS, the longevity genes of the pathway were upregulated while aging genes were downregulated.The differences were:besides IIS, Erzhi Wan affected aging mainly through regulating neuroendocrine genes and clock genes while Chuanxiong mostly affected genes of energe metabolisms, such as dietary restriction, mitochondrial activity and fat storage, etc.
Consequently, different anti-aging TCM has different molecular mechanisms.We wondered whether this character could be used to study the efficacy and component compatability of TCMs proceeded with molecular targets in the future.
In this study, we integrated several aging theories at the genetic level, which contributes to understand the relationship and regulating network among them more easily, helps to seek for the real function genes affecting aging. We considered the methods would bring great benefits for mechanism research and development of new medicine.
引文
[1]张晓文,宋清.从基因角度探讨“肾主生长发育”的本质.中医药研究,1996(03)：12-14
[2]于志恒,白雪原,陈香美.肾脏基因表达数据库的建立与肾脏衰老相关基因表达谱研究.中华肾脏病杂志,2001,17(2)：135-140
[3]高黝,高泓,,王米渠.1个糖尿病家系肾阴阳两虚血瘀证糖尿病的差异表达基因分析.现代中西医结合杂志,2005,14(01)：
[4]陈智松,潘苏彦,吴志奎.补肾生血药对衰老小鼠原癌基因c-myc表达的影响.实用老年医学,2001,15(02)：
[5]陈智松,吴志奎,陈玉英,等.枸杞多糖对衰老小鼠脑NO、NOS的影响.中药药理与临床,2000,16(06)：16-18.
[6]周坤福,王明艳,赵凤鸣,等.六味地黄丸延缓衰老作用机理的实验研究.江苏中医,1999(01).
[7]吴白燕,邹俊华,孟书聪,等.枸杞子、淫羊藿对衰老-年轻2BS融合细胞DNA合成的影响.中国中西医结合杂志,2003,23(12)：926-928
[8]王正引,张小如,兰风华,补肾健脾养血活血方对老年小鼠肾线粒体DNA缺失突变的影响.中华中医药杂志,2006,21(11)：652-654
[9]王学美,富宏,刘庚信.五子衍宗丸及其拆方对老年大鼠心脑线粒体DNA缺失、线粒体呼吸链酶复合体及ATP合成的影响.中国中西医结合杂志,2001(06).
[10]王学美,富宏,刘庚信.五子衍宗丸对男性老年肾虚者外周血白细胞线粒体DNA缺失及线粒体呼吸链酶复合体活力的影响.中国中西医结合杂志,2002(02).
[11]胡兵,安红梅,史云峰,等.补肾填精复方对WI_(38)细胞周期及相关基因表达的影响.成都中医药大学学报,2007,30(2)：35-38
[12]李国星,刘克明,何宁,等.快速老化鼠和自然衰老鼠中超氧化物歧化酶的比较研究,中国老年学杂志,2007,27：820-822
[13]李占魁.人体超氧化岐化酶的活性与年龄的关系.中日友好医学学报,1996,10(3)：209
[14]江明,李庆阳,郑旭.老年脾、肾虚与SOD关系研究.安徽中医学院学报,1999,18(6)：21
[15]江明,李庆阳,郑旭.老年脾肾虚与LPO关系研究,陕西中医学院学报,1999,22(5)：57
[16]陈丽娟,张丽宏,王兴炎,等.十精丸对老龄大鼠血清及皮肤SOD、MDA影响的实验研究.中医药学报,2007,35(5)：32-34
[17]孙兰,邹梅,张培军,等.鹿胎冲剂延缓衰老作用机理研究,中国实用医药,2007,2(8)：78-79
[18]杨婷,张冲,陈清轩.衰老机制研究进展.中国生物工程杂志,2005,25(3)：6-11
[19]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探,福建医药杂志,2000,22(1)：192
[20]王米渠,王宇,骆永珍,等.“恐伤肾”对小鼠红细胞免疫及免疫器官的影响.成都中医药大学学报,1996,19(2)：34-35.
[21]雷娓娓,黄真炎,郑高飞,等.肾虚、脾虚造型动物免疫超微结构的比较研究.深圳中西医结合杂志,1999,9(2)：14-15.
[22]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探,福建医药杂志,2000,22(1)：192
[24]王燕,董群.左归饮及其部分组方对老年小鼠细胞免疫功能的影响,中国老年学杂志,2006,
[23]陈小峰,许少峰.肾虚病人的细胞因子研究.福建中医学院学报,2000,]0(2)：12-13.26：1402-1403
[25]陈贵海,迟华基.左归饮对不同月龄衰老大鼠免疫调节作用比较辽宁中医学院学报,2006,8(2)：40-41
[26]谢红林,方艳辉,陈志,等.衰老大鼠细胞免疫功能的变化及中药天年饮的延缓衰老作用,时珍国医国药,2007,18(10)：2393-2394
[27]王虎清,吴海琴.衰老过程中神经系统的作用,国外医学·老年医学分册,2008,29(2)：53-56
[28]Meites J. Neuroendocrinology of aging.New York and London:Pleunm Press,2003,23:349
[29]沈自尹,王文健,张玲娟.从肾阳虚和老年人的不同反馈模式讨论阴阳学说.中西结合杂志,1986,6(10)：628
[30]沈自尹,王文健.肾的中西结合研究成就.中西结合杂志,1988,8(特Ⅱ集)：8-10
[31]张凤山,金友,王荣春,等.肾虚与血浆睾丸酮含量关系.中医杂志,1982,23(18)：60-61
[32]朱光楣,张越林,杨先林,等.中医肾虚与下丘脑-垂体-睾丸轴关系的探讨.天津医药,1990,32(1)：37-38
[33]张新民,沈自尹,王文健,等.补肾对神经内分泌老化调节作用研究(1).中国杂志,1991,32(11)：43态变化的影响,辽宁中医杂志,2006,33(1)：103-104
[34]龚张斌,姚建平,金国琴.补肾方药对老年大鼠下丘脑-垂体-肾上腺皮质所属组织结构形
[35]康湘萍,金国琴,龚张斌.左归丸、右归丸对老年大鼠下丘脑氨基酸类神经递质受体表达的影响,中药药理与临床,2007,23(3)：6-8
[36]杜玉珍,童建.生物钟的基因调控,生理科学进展,2002,33(4)：：343-345
[37]金戈.生物节律的分子生物学研究进展,国外医学遗传学分册,1999,22(4)：194-198
[38]顾佳黎,吴涛,童红飞,等.生物钟与衰老的相关研究进展,生理科学进展,2009,40(2)：123-]28
[1]Lin, K., et al., daf-16:An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science,1997.278(5341):p.1319-22.
[2]Lin, Y.J., L. Seroude, and S. Benzer, Extended life-span and stress resistance in the Drosophila mutant methuselah. Science,1998.282(5390):p.943-6.
[3]Guarente, L. and C. Kenyon, Genetic pathways that regulate ageing in model organisms. Nature,2000.408(6809):p.255-62.
[4]Arantes-Oliveira, N., J.R. Berman, and C. Kenyon, Healthy animals with extreme longevity. Science,2003.302(5645):p.611.
[5]Hsu, A.L., C.T. Murphy, and C. Kenyon, Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science,2003.300(5622):p.1142-5.
[6]Budovsky, A., et al., Longevity network:construction and implications. Mech Ageing Dev, 2007.128(1):p.117-24.
[7]Browner, W.S., et al., The genetics of human longevity. Am J Med,2004.117(11):p. 851-60.
[8]Sohal, R.S. and R. Weindruch, Oxidative stress, caloric restriction, and aging. Science, 1996.273(5271):p.59-63.
[9]Ozanne, S.E. and C.N. Hales, Lifespan:catch-up growth and obesity in male mice. Nature, 2004.427(6973):p.411-2.
[10]Masoro, E.J., Caloric restriction and aging:an update. Exp Gerontol,2000.35(3):p. 299-305.
[11]Mair, W., et al., Demography of dietary restriction and death in Drosophila. Science,2003. 301(5640):p.1731-3.
[12]Masoro, E.J., Overview of caloric restriction and ageing. Mech Ageing Dev,2005.126(9): p.913-22.
[13]Longo, V.D. and C.E. Finch, Evolutionary medicine:from dwarf model systems to healthy centenarians? Science,2003.299(5611):p.1342-6.
[14]de Cabo, R., et al., An in vitro model of caloric restriction. Exp Gerontol,2003.38(6):p. 631-9.
[15]Roth, G.S., D.K. Ingram, and M.A. Lane, Caloric restriction in primates and relevance to humans. Ann N Y Acad Sci,2001.928:p.305-15.
[16]Lane, M.A., et al., Caloric restriction and aging in primates:Relevance to humans and
possible CR mimetics. Microsc Res Tech,2002.59(4):p.335-8.
[17]Lakowski, B. and S. Hekimi, The genetics of caloric restriction in Caenorhabditis elegans Proc Natl Acad Sci U S A,1998.95(22):p.13091-6.
[18]Knauf, F., et al., Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc Natl Acad Sci U S A,2002.99(22):p. 14315-9.
[19]Rogina, B., S.L. Helfand, and S. Frankel, Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science,2002.298(5599):p.1745.
[20]Chen, D. and L. Guarente, SIR2:a potential target for calorie restriction mimetics. Trends Mol Med,2007.13(2):p.64-71.
[21]Klar, A.J., S. Fogel, and K. Macleod, MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE. Genetics,1979.93(1):p.37-50.
[22]Kaeberlein, M., M. McVey, and L. Guarente, The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev, 1999.13(19):p.2570-80.
[23]Tissenbaum, H.A. and L. Guarente, Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature,2001.410(6825):p.227-30.
[24]Berdichevsky, A., et al., C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell,2006.125(6):p.1165-77.
[25]Viswanathan, M., et al., A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell,2005.9(5):p.605-15.
[26]Chen, J., et al., SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem,2005.280(48):p.40364-74.
[27]Parker, J.A., et al., Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet,2005.37(4):p.349-50.
[28]Qin, W., et al., Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem,2006.281(31):p.21745-54.
[29]Vega, R.B., J.M. Huss, and D.P. Kelly, The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol,2000.20(5):p. 1868-76.
[30]Rauser, C.L., L.D. Mueller, and M.R. Rose, Dietary restriction in Drosophila. Science, 2004.303(5664):p.1610-2; author reply 1610-2.
[31]Holliday, R., Food, reproduction and longevity:is the extended lifespan of calorie-restricted animals an evolutionary adaptation? Bioessays,1989.10(4):p.125-7.
[32]Burks, D.J., et al., IRS-2 pathways integrate female reproduction and energy homeostasis. Nature,2000.407(6802):p.377-82.
[33]Kaeberlein, T.L., et al., Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell,2006.5(6):p.487-94.
[34]Tatar, M., A. Bartke, and A. Antebi, The endocrine regulation of aging by insulin-like signals. Science,2003.299(5611):p.1346-51.
[35]Longo, V.D. and P. Fabrizio, Regulation of longevity and stress resistance:a molecular strategy conserved from yeast to humans? Cell Mol Life Sci,2002.59(6):p.903-8.
[36]Garigan, D., et al., Genetic analysis of tissue aging in Caenorhabditis elegans:a role for heat-shock factor and bacterial proliferation. Genetics,2002.161(3):p.1101-12.
[37]Lin, K., et al., Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet,2001.28(2):p.139-45.
[38]Wolff, S., et al., SMK-1, an essential regulator of DAF-16-mediated longevity. Cell,2006. 124(5):p.1039-53.
[39]Morley, J.F. and R.I. Morimoto, Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell,2004.15(2):p.657-64.
[40]Clancy, D.J., et al., Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science,2001.292(5514):p.104-6.
[41]Tatar, M., et al., A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science,2001.292(5514):p.107-10.
[42]Holzenberger, M., et al., IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature,2003.421(6919):p.182-7.
[43]Bluher, M., B.B. Kahn, and C.R. Kahn, Extended longevity in mice lacking the insulin receptor in adipose tissue. Science,2003.299(5606):p.572-4.
[44]Hsieh, C.C., et al., Implications for the insulin signaling pathway in Snell dwarf mouse longevity:a similarity with the C. elegans longevity paradigm. Mech Ageing Dev,2002. 123(9):p.1229-44.
[45]Carter, C.S., et al., Models of growth hormone and 1GF-1 deficiency:applications to studies of aging processes and life-span determination. J Gerontol A Biol Sci Med Sci, 2002.57(5):p. B177-88.
[46]Coschigano, K.T., et al., Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology,2003.144(9):p.3799-810.
[47]Nemoto, S. and T. Finkel, Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science,2002.295(5564):p.2450-2.
[48]Tran, H., et al., DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein..Science,2002.296(5567):p.530-4.
[49]Laron, Z., Growth hormone insensitivity (Laron syndrome). Rev Endocr Metab Disord, 2002.3(4):p.347-55.
[50]Bonafe, M., et al., Polymorphic variants of insulin-like growth factor Ⅰ (IGF-Ⅰ) receptor and phosphoinositide 3-kinase genes affect IGF-Ⅰ plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab,2003.88(7):p.3299-304.
[51]Gray, M.D., et al., The Werner syndrome protein is a DNA helicase. Nat Genet,1997. 17(1):p.100-3.
[52]Huang, S., et al., The premature ageing syndrome protein, WRN, is a 3'->5' exonuclease. Nat Genet,1998.20(2):p.114-6.
[53]Eriksson, M., et al., Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature,2003.423(6937):p.293-8.
[54]Warner, H.R., Longevity genes:from primitive organisms to humans. Mech Ageing Dev, 2005.126(2):p.235-42.
[55]Guo, Z., K. Higuchi, and M. Mori, Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Free Radic Biol Med,2003.35(12):p.1645-52.
[56]Schachter, F., et al., Genetic associations with human longevity at the APOE and ACE loci. Nat Genet,1994.6(1):p.29-32.
[57]Rose, G., et al., Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol,2003.38(10):p.1065-70.
[1]Turnheim,Klau S.When drug therapy get sold:pharmacokinetics and pharmacodynamics in the elderly.Experimental Gerontology,2003,38(8):843-53
[2]钟星明,江丽霞,肖海,等.葛根素抗衰老作用的研究[J].时珍国医国药,2006,17(12)：2430-243]
[3]郑奕辉,李荔,张奕鹏,等.胡桃叶黄酮对D-半乳糖衰老模型小鼠的影响[J].国际医药卫生导报,2006,17(12)：2430-2431
[4]张洪泉,翁晓静,陈莉莉,等.管花肉苁蓉麦角甾苷对衰老小鼠端粒酶活性和免疫功能的影响[J].中国药理学与毒理学杂志,2008,22(4)：270-273
[5]刘晓瑞,俞仲毅.月见草油抗衰老作用的实验研究[J].中国老年学杂志,2008,27(16)：1571-72
[6]许爱霞,张振明,葛斌,等.党参多糖抗衰老作用机制的实验研究[J].中国现代应用药学杂志,2006,23(8)：729-31
[7]白雪,杨杰,刘昌福,等.延胡索总生物碱对D-半乳糖所致衰老模型小鼠相关指标的影响[J].贵州医药,2008,32(5)：399-41
[8]刘晓瑞.北五味子抗衰老作用的实验研究[J].中国老年学杂志,2005,25(12)：1562
[9]邓廷飞,梁李广.大黄抗衰老的实验研究[J].中华中医药学刊,2007,25(7)：1510-1511
[]0]谢学渊,王强.蕨麻提取物抗衰老作用研究[J].重庆医学,2007,36(8)：734-36
[11]姚丹丹,黄善华.绞股蓝对亚急性衰老大鼠的抗衰老作用研究[J].现代中西医结合杂志,2007,13(12)：4-8
[12]王爱梅,周建辉,欧阳静萍.黄精对D-半乳糖所致衰老小鼠的抗衰老作用研究[J].长春中医药大学学报,2008,24(2)：137-38
[13]李盛青,徐大量,林辉.玉竹抗衰老有效部位的药效筛选[J].中药新药与临床药理,2008,19(3)：57-58
[]4]宋巧梅.熊胆粉对D-半乳糖致衰小鼠抗衰老作用机制研究[J].江苏中医药,2006,27(8)：177-80
[15]池凤好,陈媛媛,范瑞强.二至丸加味方对D-半乳糖所致衰老模型大鼠体内自由基和免疫功能的影响[J].广州中医药大学学报,2008,25(4)：343-44
[16]周大勇.复方茶多酚胶囊抗衰老作用研究[J].实用中医药杂志,2007,23(7)：413-14
[17]高秀丽,曹恒仪,王鹏娇.丹黄通络胶囊抗衰老作用的实验研究[J].黑龙江医学,2007,31(10)：749-50
[18]陈丽艳,刘君星,施晓光.中药四君子汤抗衰老的实验研究[J].黑龙江医药,2006,19(5)：363-64
[19]沈自尹,陈瑜,黄建华,等.EF延缓HPAT轴衰老的基因表达谱研究[J].中国免疫学杂志,2004,20(1)：59-62
[20]马渊,周文霞,程军平,等.六味地黄汤对快速老化模型小鼠下丘脑-垂体-卵巢轴的调节作用及机理研究[J].中国中西医结合杂志,2004,24(4)：325-330
[21]魏小龙.海马学习记忆功能有关基因及六味地黄汤益智作用与基因表达关系的研究[J].生理科学进展,2000,31(3)：227-230
22]孙静汾，吴素慧,董进,等.复方更年康延缓老年骨质疏松雌性大鼠神经内分泌衰老
[23]牛嗣云,庞晓静,高福禄,等.松花粉对D-半乳糖亚急性衰老模型大鼠下丘脑-垂体-的实验研究[J].中国药物与临床,2006,6(12)：896-98
[24]田荣波,何宏文. 当归芍药散抗衰老作用的松果体机制[J]. 中国中西医结合杂志罩丸轴的调节作用[J].中国老年学杂志,2006,26(8)：1098-992008,28(5)：444-47
[25]许静,秦小红,薛梅.黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响[J].江苏医药,2007,33(6)：596-97
[26]韩晶利,于文丽,贾继英.野玫瑰根多糖对D-半乳糖所致衰老模型小鼠免疫功能影响的实验研究[J].中国老年学杂志,2008,28(8)：759-60
[27]王燕,董群.左归饮及其部分组方对老年小鼠细胞免疫功能的影响[J].中国老年学杂志,2006,26(10)：1042-43
[28]杨继军,佘延芬,杨阳,等.加味青麟丸提高老龄大鼠免疫能力作用的研究[J].四川中医,2008,26(4)：35-37
[29]黄伟,张旋.三七总皂苷对老龄大鼠免疫功能的影响[J].昆明医学院学报,2008,29(2)：32-35
[30]覃红斌.银杏叶提取物提高老年大鼠免疫功能及抗衰老的实验研究[J].辽宁中医杂志,2007,34(6)：836-38
[31]刘小雨,沈自尹,王琦,等.淫羊藿总黄酮(EF)对老龄大鼠Th1、Th2、Th3细胞的调节作用[J].中国免疫学杂志,2005,21(11)：842-49
[32]刘小雨,沈自尹,吴斌,等.衰老进程中大鼠淋巴细胞凋亡率的比较研究及淫羊藿总黄酮的干预作用[J].中国免疫学杂志,2007,23(9)：803-10
[33]伍倩,董淳.六味地黄汤及其补、泻组分的抗衰老作用及机制[J].中药理与临床,2003,19(3)：6-9
[34]杨靖,詹向红,孙晔,等.四君子汤对D-半乳糖衰老模型小鼠心、肝、脑组织MDA含量及端粒酶活性的影响[J].中国中西医结合杂志,2005,25(6)：531-33
[35]张士侠,李心,尹家乐,等.江苏地产白首乌C21甾苷抗衰老作用研究[J].实用老年医学,2007,21(2)：104-7
[36]赵立新,喻陆.松花粉延缓细胞衰老及对细胞端粒酶活性的影响[J].四川中医,2004,22(4)： 11-12
[37]胡作为,沈自尹,黄建华.淫羊藿总黄酮保护衰老细胞端粒长度缩短的实验研究[J].中国中西医结合杂志,2004,24(12)：1094-97
[38]赵朝晖,陈晓春,朱元贵,等.人参皂苷Rgl延缓细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国药理学通报,2005,21(1)：61-6
[39]黄浩,余南才,刘倩,等.马齿苋水提液保护衰老小鼠DNA端粒长度缩短的实验研究[J].中国临床药理学与治疗学,2007,12(7)：804-07
[40]冯全生,刘渊,周毅,等.补肾增效液对60Coγ射线小鼠脾淋巴细胞DNA损伤的影响[J].四川中医,2005,23(3)：25-26
[41]陈彪,焦淑萍,尹荣,等.6种吉林抗癌中药清除羟自由基及其抗DNA损伤体外实验研究[J].第三军医大学学报,2004,26(1)：88-89
[42]陆茵,孙志广,陈文星,等.原花青素对MNNG致DNA损伤及拓扑异构酶Ⅱ的影响[J].中药药理与临床,2003,19(1)：52-55
[43]施红,金国琴,高尤亮,等.石斛合剂对衰老糖尿病大鼠胰腺组织凋亡相关基因Bax,Bcl-2 mRNA及蛋白表达的调控[J].老年学杂志,2006,26(1)：57-60
[44]黎志萍,赵伟康,徐品初,等.益气活血方药对老年大鼠肝脏衰老相关基因表达的影响[J].中国中西医结合学报,2005,3(5)：370-73
[45]黎志萍,赵伟康,徐品初,等.补肾健脾方药对老年大鼠肝脏衰老有关基因表达的影响[J].上海中医药大学学报,2008,22(4)：61-64
[46]刘小雨,沈自尹,吴斌,等.衰老大鼠淋巴细胞磷酸化p65, IκBα, IκBε表达特点及淫羊藿总黄酮的干预研究[J].中国中药杂志,2008,33(1)：73-76
[47]王雅丽,欧芹,魏晓东,等.山茱萸多糖对衰老HDF细胞cyclinD1、CDK4表达的影 响[J].中国老年学杂志,2008,28(8)：739-41
[48]王雅丽,欧芹,魏晓东,等.山茱萸多糖对HDF细胞p-半乳糖苷酶及p16表达的影响[J].中国老年学杂志,2007,27(4)：325-27
[49]陈晓东,林建华.鹿茸多肽对大鼠软骨细胞复制性老化的作用[J].中国骨伤,2008,21 (7)：515-18
[1]王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报,2002,2002,26(4)：1249
[2]吴小明,朱美香.肝肾二脏与抗衰老的关系探讨.甘肃中医,2004,17(3)：3-5
[3]李如辉.肾脏若干基本概念的发生学思考.浙江中医学院学报,2000,24(2)：11
[4]邵英,邵华.中医肾与衰老关系的探讨—自制补肾片治疗老年虚证32例.安徽中医临床杂志,2001,13(6)：413
[5]李晓康.人之衰老,肝为先导.天津中医学院学报,1999,18(3)：3-5
[6]徐文海,徐文萍,肾气的实质及其在人体长寿中的重要作用.中国中医基础医学杂志,2001,(06).
[7]沈自尹,王文健,张玲娟,从肾阳虚和老年人的不同反馈模式讨论阴阳学说.中国中西医结合杂志,1986(10).
[8]周联,等.肾虚与脾虚动物甲状腺轴功能的比较.广州中医药大学学报,1996(02).
[9]张凤山,等.肾虚与血浆睾丸酮含量的关系—附76例血浆睾丸酮测定报告.中医杂志,1982(08).
[10]朱楣光,等.中医肾虚与下丘脑—垂体—睾丸轴关系的探讨.天津医药,1990(01).
[11]方素钦,等.中老年人肾虚证与性激素及免疫功能的研究.福建中医药,2002(02).
[12]王米渠,等.“恐伤肾”对小鼠红细胞免疫及免疫器官的影响.成都中医药大学学报,1996(02).
[13]吴玲霓,等.肾虚、脾虚造型动物免疫超微结构的比较研究.中医药研究,1999(03).
[14]武文斌,张文信,王锦丽,王玉芳,马秀伟,T淋巴细胞亚群与肾气盛衰规律的探讨.辽宁中医杂志,1995(06).
[15]李庆阳,郑家铿,老年肾虚与T细胞亚群关系.福建中医学院学报,2001(02).
[16]张家玮,金匮肾气丸对金匮肾气丸证患者T淋巴细胞亚群的影响.北京中医,2002(01).
[]7]杨嘉珍,肾虚血瘀证与红细胞免疫的关系.湖北中医杂志,1996(03).
[18]Siegel,I., T.L. Liu, and N. Gleicher, The red-cell immune system. Lancet,1981.2(8246): 556-559
[19]陈小峰,许少锋,肾虚患者的细胞因子研究.福建中医学院学报,2000(02).
[20]徐文流,周联,肾虚与脾虚模型动物IL-1的比较.广州中医药大学学报,1997(03).
[21]李文静,陈如泉,半硫丸对甲状腺机能减退肾阳虚大鼠血清SIL-2R水平影响的实验研究.辽宁中医学院学报,2002(01).
[22]宋淑霞,等.益气补肾方药对肾虚小鼠细胞因子1L-1、IL-2及lL-12基因表达的影响.中国实验动物学报,2002(02).
[23]宋淑霞,吕占军,刘福英,益气补肾方药对肾虚小鼠脾细胞CD40、CD40L:表达的调节.中华老年医学杂志,2002(05).
[24]李承军,等.老年虚证自由基代谢机理的研究.中医杂志,1988(12).
[25]薛红丽,et al.,补肾活血延缓衰老作用的实验研究.江苏中医,1999(09).
[26]陈玉碧,郭赛珊,张宏,肾虚血瘀Ⅱ型糖尿病患者红细胞SOD、血清LPO水平的观察.北京中医,1995(04).
[27]李庆阳,江明,严桂珍,老年脾肾虚证LPO、SOD、血脂及细胞免疫水平变化.福建中医学院学报,2001(03).
[28]镇而康.关于衰老与抗衰老的现代研究.国外医学,社会医学分册,2000,(24)：97
[29]黄柄山,李爱中,范隆昌,等.肝郁气滞证及其实质研究.黑龙江中医药,1998,8(3)：4
[30]李峰,杨维益.从中医学看肝脏调节应激反应的作用,北京中医药大学学报,1998,21(1)：20
[31]陈家旭。肝脏实质的研究概.浙江中医学院学报1993,17(3)：50
[32]王朝勋.怒伤肝与神经-内分泌-免疫系统失调探析.辽宁中医杂志,1997,(24)：205
[331杜艳军,康玉屏.浅析肝脾肾在衰老中的机制.江苏中医药,2003,24(11)：6-8
[34]靳晓明,董琳,范峰,等.女贞子化学成分与药理作用的研究进展.中医药信息,2008,25 (1)：40-42
[35]张振明,葛斌,许爱霞等.女贞子多糖的抗衰老作用.中国药理学与毒理学杂志,2006,20(2)：108-111
[36]黄泰康.常用中药成分与药理手册.北京：中国医药科技出版社,1994.1806-1808
[37]张金生,郭倩明.旱莲草化学成分研究.药学学报,2001,36(1)：34-37
[38]李弋,周 琳,杨风云.旱莲草对D2半乳糖所致亚急性衰老小鼠的抗衰老作用研究.山西医科大学学报,2005,36(5)：574-576
[39]王淑梅,王灿岭.二至丸对亚急性衰老模型小鼠抗衰老作用的实验研究.中医研究,2006,19(5)：21-22.
[40]赵雪莹,李胜志,李冀.二至丸对衰老大鼠血液流变学影响的实验研究.辽宁中医杂志,2008,35(6)：945-946.
[41]孙洪涛.二至丸对衰老小鼠模型脑细胞N a+-K+-ATP酶、C a2+-ATP酶活性影响的研究.中外医疗,2008(13)：78.
[42]李弋,杨友谊.中药二至丸对老年痴呆模型小鼠脑组织N a+-K+-ATPase、Ca2+-ATPase活性及学习记忆的影响.广州医学院学报,2005,33(3)：23-25.
[43]刘大基,刘解生,徐继勋,等.二至丸对小鼠淋巴细胞免疫功能的调节作用.湖北中医杂志,2002,24(2)：48-49.
[44]操红缨,梁颂名,荣向路,等.二至丸对阴虚模型神经内分泌免疫网络调节作用的研究.中药材,2000,23(3)：164-166.
[45]高会丽,王丹巧,汪晓燕.二至丸抗衰老大鼠神经细胞凋亡的实验研究.
[46]颜德馨.气血与衰老.江苏中医,1990,(4)：27
[47]韩明向.“虚-瘀-衰老”模式初探.安徽中医学院学报,1992,11(3)：2
[48]颜德馨.中国历代中医抗衰老秘要.文汇出版社,1993
[49]颜德馨。气虚血瘀是人体衰老的主要机制.中国医药学报,1989,2：10-12
[50]韩明向.老年虚证与SOD及中药提高SOD活性的研究.安徽中医学院学报,1991,10(4)：64
[51]王香婷,朱晓红,魏民等.补气活血方药对衰老性急性肺损伤大鼠SOD及MDA的影响.中国中医基础医学杂志.2009,15(6)：435-436
[52]毛腾敏.丹参、当归对老年大鼠血瘀的影响.中西医结合杂志,1988,8(10)：635
[53]詹小萍,孙梅,金晓滢等.益肾活血方对家兔血瘀模型纤溶指标与血液流变学影响的研究.中国中药杂志,2006,31(5)：411-413
[54]刘礼意.益气活血方对老年大鼠神经免疫调节影响的研究.中国中西医结合杂志,1997,17(10)：616
[55]黄华永,沈海星,郑锦鸿.阿魏酸及其类似物的合成及其清除自由基活性研究.中国新药杂志,2006(6)：236-237
[56]徐升强,贾岷.川芎嗪对急性胰腺炎大鼠细胞凋亡的影响.微循环学杂志,2009,19(2)：25-28
[57]胡燕月,阮琴,徐叶芬等.川芎嗪和阿魏酸对大鼠离体心脏血流动力学的影响.浙江师范大学学报(自然科学版),2004,4(3)：382-385.
[58]杨静,雷燕,崔巍等.人参三七川芎提取物延缓内皮细胞复制性衰老的机制研究.中国中药杂志,2009,34(12)：1544-1548
[59]董晓华,张丹参,武海霞,衰老动物模型的研究进展及评价.河北北方学院学报,2004(06).
[60]Frisard, M. and E. Ravussin, Energy metabolism and oxidative stress:impact on the metabolic syndrome and the aging process. Endocrine,2006.29(1):p.27-32.
[61]马宏,张宗玉,童坦君,衰老的生物学标志.生理科学进展,2002(01).
[62]Sohal, R.S. and R. Weindruch, Oxidative stress, caloric restriction, and aging. Science,1996. 273(5271):59-63.
[63]Ozanne, S.E. and C.N. Hales, Lifespan:catch-up growth and obesity in male mice. Nature, 2004.427(6973):p.411-2.
[64]Mair, W., et al., Demography of dietary restriction and death in Drosophila. Science,2003. 301 (5640):1731-1733
[65]Masoro, E.J., Overview of caloric restriction and ageing. Mech Ageing Dev,2005.126(9): 913-22.
[66]沈自尹,淫羊藿总黄酮延缓衰老的研究.世界科学技术-中医药现代化,2005(01).
[67]黎志萍,赵伟康,徐品初,等.益气活血方药对老年大鼠肝脏衰老相关基因表达的影响,中西医结合学报,2005,3(5)：370-373
[68]周明学,徐浩,潘琳,等.活血、益气、化痰中药对ApoE基因敲除小鼠主动脉粥样硬化斑块炎症反应的影响.中国中医急症,2008,17(4)：496-498
[69]杨靖,詹向红,孙哗,等.四君子汤对D2半乳糖衰老模型小鼠心、肝、脑组织MDA含量及端粒酶活性的影响,中国中西医结合杂志,2005,25(6)：531-533
[70]Erik M. Jorgensen and Susan E.Mango. The art and desige of genetic screens:caenorhabditis elegans. Nature Reviews Genetics.2002,3,356-369
[71]Sulston,J.E.,Horvitz,H.R.Post-embryonic cell lineages of the nematode Caenorhabditiselegans. Dev. Biol.1997,56,110-156
[72]Bargmann CI. Neurobioligy of the Caenorhabditis elegans genome. Science,1998.282: 2028-2033
[73]Vanfleteren, J.R., Braeckman, B.P.. Mechanisms of life span determination in Caenorhabditis elegans. Neurobiol. Aging,1999,20,487-502.
[74]Hobert, O., Behavioral plasticity in C.elegans:Paradigms, circuits, genes. J Neurobiol.2003, 54(1):203-223
[75]Harriet Gershon, David Gershon. Caenorhabditis elegans-a paradigm for aging research: advantages and limitations. Mechanisms of Ageing and Development,2002,123:261-274
[76]蔡外娇,张新民,黄建华,等.淫羊藿总黄酮延缓秀丽隐杆线虫衰老的实验研究,中国中西医结合杂志,2008,28(6)：522-525
[77]Mark A. Wilson, Barbara Shukitt-Hale, Wilhelmina Kalt, et al. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans, Aging Cell,2006,5,59-68
[78]Brenner, S. The genetics of Caenorhabditis elegans. Genetics,1974,77:71-94
[79]Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-△ △Ct method. Methods,2001,25:402-408
[80]李春生,侯荣先.国内应用寿命试验和衰老动物模型研究抗衰老中药的近室内概况.中医杂志,1998；39(11)：690-693
[81]Evason K, Huang C, Yamben I, et al. Anticonvulsant medications extend worm life-span. Science,2005,307 (12):258-62
[82]冀敦福,季海刚.关于衰老与老年病中医机制的探讨.天津中医学院学报,2004,23(4)：169
[83]于英军,管宇,宋高臣.蜂胶对果蝇寿命的影响,中医药学报,2004,32(5)：53-54
[84]Partridge, L. et al. Sex and death:what is the connection? Cell,2005,120,461-472
[85]Mukhopadhyay A, Tissenbaum HA. Reproduction and longevity:secrets revealed by C.elegans. Trands Cell Biol,2007,17(2):65-71
[86]Kenyon C. The plasticity of aging:insights from long-lived mutants. Cell,2005,120 (4): 449-460
[87]Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science,2003,299(5611):1346-1351
[88]Browner, W.S., et al., The genetics of human longevity. American Journal of Medicine,2004. 117(11):p.851-860
[89]Braeckman B. P., Vanfleteren J. R. Genetic control of longevity in C. elegans. Experimental Gerontology,2007,42:90-98
[90]Ailion, M., T. Inoue, C. I. Weaver, R. W. Holdcraft, et al. Neurosecretory control of aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA,1999,96:7394-7397.
[91]Manuel J. Munoz, Donald L. Riddle. Positive Selection of Caenorhabditis elegans Mutants With Increased Stress Resistance and Longevity. Genetics,2003,163:171-180
[92]Adam Antebi. Genetics of Aging in Caenorhabditis elegans. PLoS Genetics,2007,3(9):1565-1571
[93]Hristova M, Birse D, Hong Y, Ambros V. The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding. Mol Cell Biol.2005,25:11059-11072.
[94]马永兴,俞卓伟主编.现代衰老学,2008,p496
[95]Bernard Lakowski, Siegfried Hekimi. Determination of life-span in caenorhabditis elegans by four clock genes. Science,1996,272:1010-1013
[96]Chang-Su Lim, I. Saira Mian, Abby F. Dernburg,et al. C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p.
[97]Lemieux, J., Lakowski, B., Webb, A.,et al. Regulation of physiological rates in Current Biology,2001,11:1706-1710 Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria. Genetics, 2001,159,147-157.
[98]Bart P. Braeckman, Koen Houthoofd, Annemie De Vreese,et al. Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans. Current Biology 1999,9(9):493-496
[99]林水森,周如倩.中医论衰老机理,上海中医药杂志,1994,12：14-16
[100]王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报,2002,2002,26(4)：249
[101]吴小明,朱美香,李如辉.肝肾二脏与抗衰老的关系探讨.甘肃中医,2004,17(3)：3-6
[102]陆秀兰.生物钟与衰老.辽宁中医杂志,1998,25(11)：509-511
[103]顾佳黎,吴,涛,童红飞,等.生物钟与衰老的相关研究进展.生理科学进展,2009,40(2)：123-128
[104]颜德馨.中国历代中医抗衰老秘要.文汇出版社,1993
[105]刘士豪.塞里应激学概要.上海：上海科学技术出版社,1963,21
[106]Selye H. Stress and aging. J Am Ger Soci,1970,18:669-679
[107]Tissieres A, Mitchell H K, Tracy U M. Protein synthesis in salivary glands of Drosophila melanogaster in relation to chromosome puffs. J. Mol. Biol.1974,84:389-398
[108]孙秀兰.从自由基角度研究应激与衰老的关系.中国行为医学科学,1998,7(1)：73-76
[109]Lithgow GJ, Walker GA. Stress resistance as a determinate of C.elegans lifespan. Mech Ageing Dev,2002,123(7):765-771
[110]Tsui D,van der Kooy D.Serotonin mediates a learned increase in attraction to high concentrations of benzaldehyde in aged C. elegans. Learning & Memory.2008 Oct 30; 15(11):844-855
[111]Pierce SB, Costa M, Wisotzkey R,et al. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. GeneDevelopment.2001,15(6):672-686
[112]Tissenbaum, H.A., Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature.2001,410,227-230
[113]Yoko Honda,Shuji Honda. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. The FASEB Journal.1999,13:1385-1393
[114]Manoj Nanji, Neil A. Hopper, David Gems. LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell.2005,4,235-245
[115]Masoro EJ.Overview of caloric restriction and ageing. Mechanism of Aging and Development,2005,126:913-922
[116]Guarente L, Picard F. Calorie restriction2the SIR2 connection.Cell,2005,120 (4):473-482
[117]Tissenbaum, H.A., Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature.2001,410,227-230.
[118]Vellai T, Takacs-Vellai K, Zhang Y, et al. Genetics:influence of TOR kinase on lifespan in C. elegans. Nature,2003,426:620
[119]Kailiang Jia, Di Chen, Donald L. Riddle. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development.2004,131,3897-3906
[120]刘小雨,王琦,夏世金,等.增龄进程淋巴细胞核转录因子κB相关基因表达及淫羊藿总黄酮的调控作用.中医杂志,2009,50(1)：66-68
[121]Jennifer M. A. Tullet, Maren Hertweck, Jae Hyung An,etc. Direct inhibition of the longevity promoting factor SKN-1 by Insulin-like signaling in C. elegans. Cell.2008 March 21; 132(6):1025-1038.
[122]Bishop NA, Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature,2007,447 (7144):545-549
[123]Kiang JG, Tsokos G. Heat Shock Protein 70 kDa:Molecular Biology, Biochemistry, and Physiology. Pharmacol Ther,1998,80:183-201
[124]Caminsi A, Diez-fernandez C, Prieto P. Cell Expression of Heat Shock Proteins in Dog Neutrophils after Oxidative Stress. Toxicology in Vitro,1000,13:437-443
[125]Morita K, Saito T, Ohta M, et al. Expression analysis of psychological stress-associated genes in peripheral blood leukocytes. Neuroscience Letters,2005,381:57-62
[126]Oehler R, Pusch E, Zellner M, et al. Cell type-specific variations in the induction of hsp70 in human leukocytes by feverlike whole body hyperthermia. Cell Stress Chaperones,2001,6: 306-315
[127]王玮文,邵枫,刘美,等.衰老、慢性应激与免疫细胞热休克蛋白70反应抑制.中国行为医学科学,2007,16(10)：951-953
[128]马永兴,俞卓伟主编.现代衰老学,2008,141
[129]Vijg J, Suh Y. Functional Genomics of Ageing. Mechanisms of Ageing and Development, 2003,124:3-8
[130]马永兴,俞卓伟主编.现代衰老学,2008,1345-1350
[131]陈方敏,赵伟康,徐品初,等.补肾、健脾、益气、活血法对衰老细胞周期基因表达的调控作用.中国中西医结合杂志,2003,23(11)：837-840
[2]于志恒,白雪原,陈香美.肾脏基因表达数据库的建立与肾脏衰老相关基因表达谱研究.中华肾脏病杂志,2001,17(2)：135-140
[3]高黝,高泓,,王米渠.1个糖尿病家系肾阴阳两虚血瘀证糖尿病的差异表达基因分析.现代中西医结合杂志,2005,14(01)：
[4]陈智松,潘苏彦,吴志奎.补肾生血药对衰老小鼠原癌基因c-myc表达的影响.实用老年医学,2001,15(02)：
[5]陈智松,吴志奎,陈玉英,等.枸杞多糖对衰老小鼠脑NO、NOS的影响.中药药理与临床,2000,16(06)：16-18.
[6]周坤福,王明艳,赵凤鸣,等.六味地黄丸延缓衰老作用机理的实验研究.江苏中医,1999(01).
[7]吴白燕,邹俊华,孟书聪,等.枸杞子、淫羊藿对衰老-年轻2BS融合细胞DNA合成的影响.中国中西医结合杂志,2003,23(12)：926-928
[8]王正引,张小如,兰风华,补肾健脾养血活血方对老年小鼠肾线粒体DNA缺失突变的影响.中华中医药杂志,2006,21(11)：652-654
[9]王学美,富宏,刘庚信.五子衍宗丸及其拆方对老年大鼠心脑线粒体DNA缺失、线粒体呼吸链酶复合体及ATP合成的影响.中国中西医结合杂志,2001(06).
[10]王学美,富宏,刘庚信.五子衍宗丸对男性老年肾虚者外周血白细胞线粒体DNA缺失及线粒体呼吸链酶复合体活力的影响.中国中西医结合杂志,2002(02).
[11]胡兵,安红梅,史云峰,等.补肾填精复方对WI_(38)细胞周期及相关基因表达的影响.成都中医药大学学报,2007,30(2)：35-38
[12]李国星,刘克明,何宁,等.快速老化鼠和自然衰老鼠中超氧化物歧化酶的比较研究,中国老年学杂志,2007,27：820-822
[13]李占魁.人体超氧化岐化酶的活性与年龄的关系.中日友好医学学报,1996,10(3)：209
[14]江明,李庆阳,郑旭.老年脾、肾虚与SOD关系研究.安徽中医学院学报,1999,18(6)：21
[15]江明,李庆阳,郑旭.老年脾肾虚与LPO关系研究,陕西中医学院学报,1999,22(5)：57
[16]陈丽娟,张丽宏,王兴炎,等.十精丸对老龄大鼠血清及皮肤SOD、MDA影响的实验研究.中医药学报,2007,35(5)：32-34
[17]孙兰,邹梅,张培军,等.鹿胎冲剂延缓衰老作用机理研究,中国实用医药,2007,2(8)：78-79
[18]杨婷,张冲,陈清轩.衰老机制研究进展.中国生物工程杂志,2005,25(3)：6-11
[19]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探,福建医药杂志,2000,22(1)：192
[20]王米渠,王宇,骆永珍,等.“恐伤肾”对小鼠红细胞免疫及免疫器官的影响.成都中医药大学学报,1996,19(2)：34-35.
[21]雷娓娓,黄真炎,郑高飞,等.肾虚、脾虚造型动物免疫超微结构的比较研究.深圳中西医结合杂志,1999,9(2)：14-15.
[22]林礼兴,林丽婷,雷焕英,等.衰老与肾虚症及T细胞亚群间关系初探,福建医药杂志,2000,22(1)：192
[24]王燕,董群.左归饮及其部分组方对老年小鼠细胞免疫功能的影响,中国老年学杂志,2006,
[23]陈小峰,许少峰.肾虚病人的细胞因子研究.福建中医学院学报,2000,]0(2)：12-13.26：1402-1403
[25]陈贵海,迟华基.左归饮对不同月龄衰老大鼠免疫调节作用比较辽宁中医学院学报,2006,8(2)：40-41
[26]谢红林,方艳辉,陈志,等.衰老大鼠细胞免疫功能的变化及中药天年饮的延缓衰老作用,时珍国医国药,2007,18(10)：2393-2394
[27]王虎清,吴海琴.衰老过程中神经系统的作用,国外医学·老年医学分册,2008,29(2)：53-56
[28]Meites J. Neuroendocrinology of aging.New York and London:Pleunm Press,2003,23:349
[29]沈自尹,王文健,张玲娟.从肾阳虚和老年人的不同反馈模式讨论阴阳学说.中西结合杂志,1986,6(10)：628
[30]沈自尹,王文健.肾的中西结合研究成就.中西结合杂志,1988,8(特Ⅱ集)：8-10
[31]张凤山,金友,王荣春,等.肾虚与血浆睾丸酮含量关系.中医杂志,1982,23(18)：60-61
[32]朱光楣,张越林,杨先林,等.中医肾虚与下丘脑-垂体-睾丸轴关系的探讨.天津医药,1990,32(1)：37-38
[33]张新民,沈自尹,王文健,等.补肾对神经内分泌老化调节作用研究(1).中国杂志,1991,32(11)：43态变化的影响,辽宁中医杂志,2006,33(1)：103-104
[34]龚张斌,姚建平,金国琴.补肾方药对老年大鼠下丘脑-垂体-肾上腺皮质所属组织结构形
[35]康湘萍,金国琴,龚张斌.左归丸、右归丸对老年大鼠下丘脑氨基酸类神经递质受体表达的影响,中药药理与临床,2007,23(3)：6-8
[36]杜玉珍,童建.生物钟的基因调控,生理科学进展,2002,33(4)：：343-345
[37]金戈.生物节律的分子生物学研究进展,国外医学遗传学分册,1999,22(4)：194-198
[38]顾佳黎,吴涛,童红飞,等.生物钟与衰老的相关研究进展,生理科学进展,2009,40(2)：123-]28
[1]Lin, K., et al., daf-16:An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science,1997.278(5341):p.1319-22.
[2]Lin, Y.J., L. Seroude, and S. Benzer, Extended life-span and stress resistance in the Drosophila mutant methuselah. Science,1998.282(5390):p.943-6.
[3]Guarente, L. and C. Kenyon, Genetic pathways that regulate ageing in model organisms. Nature,2000.408(6809):p.255-62.
[4]Arantes-Oliveira, N., J.R. Berman, and C. Kenyon, Healthy animals with extreme longevity. Science,2003.302(5645):p.611.
[5]Hsu, A.L., C.T. Murphy, and C. Kenyon, Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science,2003.300(5622):p.1142-5.
[6]Budovsky, A., et al., Longevity network:construction and implications. Mech Ageing Dev, 2007.128(1):p.117-24.
[7]Browner, W.S., et al., The genetics of human longevity. Am J Med,2004.117(11):p. 851-60.
[8]Sohal, R.S. and R. Weindruch, Oxidative stress, caloric restriction, and aging. Science, 1996.273(5271):p.59-63.
[9]Ozanne, S.E. and C.N. Hales, Lifespan:catch-up growth and obesity in male mice. Nature, 2004.427(6973):p.411-2.
[10]Masoro, E.J., Caloric restriction and aging:an update. Exp Gerontol,2000.35(3):p. 299-305.
[11]Mair, W., et al., Demography of dietary restriction and death in Drosophila. Science,2003. 301(5640):p.1731-3.
[12]Masoro, E.J., Overview of caloric restriction and ageing. Mech Ageing Dev,2005.126(9): p.913-22.
[13]Longo, V.D. and C.E. Finch, Evolutionary medicine:from dwarf model systems to healthy centenarians? Science,2003.299(5611):p.1342-6.
[14]de Cabo, R., et al., An in vitro model of caloric restriction. Exp Gerontol,2003.38(6):p. 631-9.
[15]Roth, G.S., D.K. Ingram, and M.A. Lane, Caloric restriction in primates and relevance to humans. Ann N Y Acad Sci,2001.928:p.305-15.
[16]Lane, M.A., et al., Caloric restriction and aging in primates:Relevance to humans and
possible CR mimetics. Microsc Res Tech,2002.59(4):p.335-8.
[17]Lakowski, B. and S. Hekimi, The genetics of caloric restriction in Caenorhabditis elegans Proc Natl Acad Sci U S A,1998.95(22):p.13091-6.
[18]Knauf, F., et al., Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc Natl Acad Sci U S A,2002.99(22):p. 14315-9.
[19]Rogina, B., S.L. Helfand, and S. Frankel, Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science,2002.298(5599):p.1745.
[20]Chen, D. and L. Guarente, SIR2:a potential target for calorie restriction mimetics. Trends Mol Med,2007.13(2):p.64-71.
[21]Klar, A.J., S. Fogel, and K. Macleod, MAR1-a Regulator of the HMa and HMalpha Loci in SACCHAROMYCES CEREVISIAE. Genetics,1979.93(1):p.37-50.
[22]Kaeberlein, M., M. McVey, and L. Guarente, The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev, 1999.13(19):p.2570-80.
[23]Tissenbaum, H.A. and L. Guarente, Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature,2001.410(6825):p.227-30.
[24]Berdichevsky, A., et al., C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell,2006.125(6):p.1165-77.
[25]Viswanathan, M., et al., A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Dev Cell,2005.9(5):p.605-15.
[26]Chen, J., et al., SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J Biol Chem,2005.280(48):p.40364-74.
[27]Parker, J.A., et al., Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet,2005.37(4):p.349-50.
[28]Qin, W., et al., Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem,2006.281(31):p.21745-54.
[29]Vega, R.B., J.M. Huss, and D.P. Kelly, The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol,2000.20(5):p. 1868-76.
[30]Rauser, C.L., L.D. Mueller, and M.R. Rose, Dietary restriction in Drosophila. Science, 2004.303(5664):p.1610-2; author reply 1610-2.
[31]Holliday, R., Food, reproduction and longevity:is the extended lifespan of calorie-restricted animals an evolutionary adaptation? Bioessays,1989.10(4):p.125-7.
[32]Burks, D.J., et al., IRS-2 pathways integrate female reproduction and energy homeostasis. Nature,2000.407(6802):p.377-82.
[33]Kaeberlein, T.L., et al., Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell,2006.5(6):p.487-94.
[34]Tatar, M., A. Bartke, and A. Antebi, The endocrine regulation of aging by insulin-like signals. Science,2003.299(5611):p.1346-51.
[35]Longo, V.D. and P. Fabrizio, Regulation of longevity and stress resistance:a molecular strategy conserved from yeast to humans? Cell Mol Life Sci,2002.59(6):p.903-8.
[36]Garigan, D., et al., Genetic analysis of tissue aging in Caenorhabditis elegans:a role for heat-shock factor and bacterial proliferation. Genetics,2002.161(3):p.1101-12.
[37]Lin, K., et al., Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet,2001.28(2):p.139-45.
[38]Wolff, S., et al., SMK-1, an essential regulator of DAF-16-mediated longevity. Cell,2006. 124(5):p.1039-53.
[39]Morley, J.F. and R.I. Morimoto, Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell,2004.15(2):p.657-64.
[40]Clancy, D.J., et al., Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science,2001.292(5514):p.104-6.
[41]Tatar, M., et al., A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science,2001.292(5514):p.107-10.
[42]Holzenberger, M., et al., IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature,2003.421(6919):p.182-7.
[43]Bluher, M., B.B. Kahn, and C.R. Kahn, Extended longevity in mice lacking the insulin receptor in adipose tissue. Science,2003.299(5606):p.572-4.
[44]Hsieh, C.C., et al., Implications for the insulin signaling pathway in Snell dwarf mouse longevity:a similarity with the C. elegans longevity paradigm. Mech Ageing Dev,2002. 123(9):p.1229-44.
[45]Carter, C.S., et al., Models of growth hormone and 1GF-1 deficiency:applications to studies of aging processes and life-span determination. J Gerontol A Biol Sci Med Sci, 2002.57(5):p. B177-88.
[46]Coschigano, K.T., et al., Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology,2003.144(9):p.3799-810.
[47]Nemoto, S. and T. Finkel, Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science,2002.295(5564):p.2450-2.
[48]Tran, H., et al., DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein..Science,2002.296(5567):p.530-4.
[49]Laron, Z., Growth hormone insensitivity (Laron syndrome). Rev Endocr Metab Disord, 2002.3(4):p.347-55.
[50]Bonafe, M., et al., Polymorphic variants of insulin-like growth factor Ⅰ (IGF-Ⅰ) receptor and phosphoinositide 3-kinase genes affect IGF-Ⅰ plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab,2003.88(7):p.3299-304.
[51]Gray, M.D., et al., The Werner syndrome protein is a DNA helicase. Nat Genet,1997. 17(1):p.100-3.
[52]Huang, S., et al., The premature ageing syndrome protein, WRN, is a 3'->5' exonuclease. Nat Genet,1998.20(2):p.114-6.
[53]Eriksson, M., et al., Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature,2003.423(6937):p.293-8.
[54]Warner, H.R., Longevity genes:from primitive organisms to humans. Mech Ageing Dev, 2005.126(2):p.235-42.
[55]Guo, Z., K. Higuchi, and M. Mori, Spontaneous hypomorphic mutations in antioxidant enzymes of mice. Free Radic Biol Med,2003.35(12):p.1645-52.
[56]Schachter, F., et al., Genetic associations with human longevity at the APOE and ACE loci. Nat Genet,1994.6(1):p.29-32.
[57]Rose, G., et al., Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol,2003.38(10):p.1065-70.
[1]Turnheim,Klau S.When drug therapy get sold:pharmacokinetics and pharmacodynamics in the elderly.Experimental Gerontology,2003,38(8):843-53
[2]钟星明,江丽霞,肖海,等.葛根素抗衰老作用的研究[J].时珍国医国药,2006,17(12)：2430-243]
[3]郑奕辉,李荔,张奕鹏,等.胡桃叶黄酮对D-半乳糖衰老模型小鼠的影响[J].国际医药卫生导报,2006,17(12)：2430-2431
[4]张洪泉,翁晓静,陈莉莉,等.管花肉苁蓉麦角甾苷对衰老小鼠端粒酶活性和免疫功能的影响[J].中国药理学与毒理学杂志,2008,22(4)：270-273
[5]刘晓瑞,俞仲毅.月见草油抗衰老作用的实验研究[J].中国老年学杂志,2008,27(16)：1571-72
[6]许爱霞,张振明,葛斌,等.党参多糖抗衰老作用机制的实验研究[J].中国现代应用药学杂志,2006,23(8)：729-31
[7]白雪,杨杰,刘昌福,等.延胡索总生物碱对D-半乳糖所致衰老模型小鼠相关指标的影响[J].贵州医药,2008,32(5)：399-41
[8]刘晓瑞.北五味子抗衰老作用的实验研究[J].中国老年学杂志,2005,25(12)：1562
[9]邓廷飞,梁李广.大黄抗衰老的实验研究[J].中华中医药学刊,2007,25(7)：1510-1511
[]0]谢学渊,王强.蕨麻提取物抗衰老作用研究[J].重庆医学,2007,36(8)：734-36
[11]姚丹丹,黄善华.绞股蓝对亚急性衰老大鼠的抗衰老作用研究[J].现代中西医结合杂志,2007,13(12)：4-8
[12]王爱梅,周建辉,欧阳静萍.黄精对D-半乳糖所致衰老小鼠的抗衰老作用研究[J].长春中医药大学学报,2008,24(2)：137-38
[13]李盛青,徐大量,林辉.玉竹抗衰老有效部位的药效筛选[J].中药新药与临床药理,2008,19(3)：57-58
[]4]宋巧梅.熊胆粉对D-半乳糖致衰小鼠抗衰老作用机制研究[J].江苏中医药,2006,27(8)：177-80
[15]池凤好,陈媛媛,范瑞强.二至丸加味方对D-半乳糖所致衰老模型大鼠体内自由基和免疫功能的影响[J].广州中医药大学学报,2008,25(4)：343-44
[16]周大勇.复方茶多酚胶囊抗衰老作用研究[J].实用中医药杂志,2007,23(7)：413-14
[17]高秀丽,曹恒仪,王鹏娇.丹黄通络胶囊抗衰老作用的实验研究[J].黑龙江医学,2007,31(10)：749-50
[18]陈丽艳,刘君星,施晓光.中药四君子汤抗衰老的实验研究[J].黑龙江医药,2006,19(5)：363-64
[19]沈自尹,陈瑜,黄建华,等.EF延缓HPAT轴衰老的基因表达谱研究[J].中国免疫学杂志,2004,20(1)：59-62
[20]马渊,周文霞,程军平,等.六味地黄汤对快速老化模型小鼠下丘脑-垂体-卵巢轴的调节作用及机理研究[J].中国中西医结合杂志,2004,24(4)：325-330
[21]魏小龙.海马学习记忆功能有关基因及六味地黄汤益智作用与基因表达关系的研究[J].生理科学进展,2000,31(3)：227-230
22]孙静汾，吴素慧,董进,等.复方更年康延缓老年骨质疏松雌性大鼠神经内分泌衰老
[23]牛嗣云,庞晓静,高福禄,等.松花粉对D-半乳糖亚急性衰老模型大鼠下丘脑-垂体-的实验研究[J].中国药物与临床,2006,6(12)：896-98
[24]田荣波,何宏文. 当归芍药散抗衰老作用的松果体机制[J]. 中国中西医结合杂志罩丸轴的调节作用[J].中国老年学杂志,2006,26(8)：1098-992008,28(5)：444-47
[25]许静,秦小红,薛梅.黄芪对D-半乳糖衰老大鼠脂质过氧化及红细胞免疫功能的影响[J].江苏医药,2007,33(6)：596-97
[26]韩晶利,于文丽,贾继英.野玫瑰根多糖对D-半乳糖所致衰老模型小鼠免疫功能影响的实验研究[J].中国老年学杂志,2008,28(8)：759-60
[27]王燕,董群.左归饮及其部分组方对老年小鼠细胞免疫功能的影响[J].中国老年学杂志,2006,26(10)：1042-43
[28]杨继军,佘延芬,杨阳,等.加味青麟丸提高老龄大鼠免疫能力作用的研究[J].四川中医,2008,26(4)：35-37
[29]黄伟,张旋.三七总皂苷对老龄大鼠免疫功能的影响[J].昆明医学院学报,2008,29(2)：32-35
[30]覃红斌.银杏叶提取物提高老年大鼠免疫功能及抗衰老的实验研究[J].辽宁中医杂志,2007,34(6)：836-38
[31]刘小雨,沈自尹,王琦,等.淫羊藿总黄酮(EF)对老龄大鼠Th1、Th2、Th3细胞的调节作用[J].中国免疫学杂志,2005,21(11)：842-49
[32]刘小雨,沈自尹,吴斌,等.衰老进程中大鼠淋巴细胞凋亡率的比较研究及淫羊藿总黄酮的干预作用[J].中国免疫学杂志,2007,23(9)：803-10
[33]伍倩,董淳.六味地黄汤及其补、泻组分的抗衰老作用及机制[J].中药理与临床,2003,19(3)：6-9
[34]杨靖,詹向红,孙晔,等.四君子汤对D-半乳糖衰老模型小鼠心、肝、脑组织MDA含量及端粒酶活性的影响[J].中国中西医结合杂志,2005,25(6)：531-33
[35]张士侠,李心,尹家乐,等.江苏地产白首乌C21甾苷抗衰老作用研究[J].实用老年医学,2007,21(2)：104-7
[36]赵立新,喻陆.松花粉延缓细胞衰老及对细胞端粒酶活性的影响[J].四川中医,2004,22(4)： 11-12
[37]胡作为,沈自尹,黄建华.淫羊藿总黄酮保护衰老细胞端粒长度缩短的实验研究[J].中国中西医结合杂志,2004,24(12)：1094-97
[38]赵朝晖,陈晓春,朱元贵,等.人参皂苷Rgl延缓细胞衰老过程中端粒长度和端粒酶活性的变化[J].中国药理学通报,2005,21(1)：61-6
[39]黄浩,余南才,刘倩,等.马齿苋水提液保护衰老小鼠DNA端粒长度缩短的实验研究[J].中国临床药理学与治疗学,2007,12(7)：804-07
[40]冯全生,刘渊,周毅,等.补肾增效液对60Coγ射线小鼠脾淋巴细胞DNA损伤的影响[J].四川中医,2005,23(3)：25-26
[41]陈彪,焦淑萍,尹荣,等.6种吉林抗癌中药清除羟自由基及其抗DNA损伤体外实验研究[J].第三军医大学学报,2004,26(1)：88-89
[42]陆茵,孙志广,陈文星,等.原花青素对MNNG致DNA损伤及拓扑异构酶Ⅱ的影响[J].中药药理与临床,2003,19(1)：52-55
[43]施红,金国琴,高尤亮,等.石斛合剂对衰老糖尿病大鼠胰腺组织凋亡相关基因Bax,Bcl-2 mRNA及蛋白表达的调控[J].老年学杂志,2006,26(1)：57-60
[44]黎志萍,赵伟康,徐品初,等.益气活血方药对老年大鼠肝脏衰老相关基因表达的影响[J].中国中西医结合学报,2005,3(5)：370-73
[45]黎志萍,赵伟康,徐品初,等.补肾健脾方药对老年大鼠肝脏衰老有关基因表达的影响[J].上海中医药大学学报,2008,22(4)：61-64
[46]刘小雨,沈自尹,吴斌,等.衰老大鼠淋巴细胞磷酸化p65, IκBα, IκBε表达特点及淫羊藿总黄酮的干预研究[J].中国中药杂志,2008,33(1)：73-76
[47]王雅丽,欧芹,魏晓东,等.山茱萸多糖对衰老HDF细胞cyclinD1、CDK4表达的影 响[J].中国老年学杂志,2008,28(8)：739-41
[48]王雅丽,欧芹,魏晓东,等.山茱萸多糖对HDF细胞p-半乳糖苷酶及p16表达的影响[J].中国老年学杂志,2007,27(4)：325-27
[49]陈晓东,林建华.鹿茸多肽对大鼠软骨细胞复制性老化的作用[J].中国骨伤,2008,21 (7)：515-18
[1]王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报,2002,2002,26(4)：1249
[2]吴小明,朱美香.肝肾二脏与抗衰老的关系探讨.甘肃中医,2004,17(3)：3-5
[3]李如辉.肾脏若干基本概念的发生学思考.浙江中医学院学报,2000,24(2)：11
[4]邵英,邵华.中医肾与衰老关系的探讨—自制补肾片治疗老年虚证32例.安徽中医临床杂志,2001,13(6)：413
[5]李晓康.人之衰老,肝为先导.天津中医学院学报,1999,18(3)：3-5
[6]徐文海,徐文萍,肾气的实质及其在人体长寿中的重要作用.中国中医基础医学杂志,2001,(06).
[7]沈自尹,王文健,张玲娟,从肾阳虚和老年人的不同反馈模式讨论阴阳学说.中国中西医结合杂志,1986(10).
[8]周联,等.肾虚与脾虚动物甲状腺轴功能的比较.广州中医药大学学报,1996(02).
[9]张凤山,等.肾虚与血浆睾丸酮含量的关系—附76例血浆睾丸酮测定报告.中医杂志,1982(08).
[10]朱楣光,等.中医肾虚与下丘脑—垂体—睾丸轴关系的探讨.天津医药,1990(01).
[11]方素钦,等.中老年人肾虚证与性激素及免疫功能的研究.福建中医药,2002(02).
[12]王米渠,等.“恐伤肾”对小鼠红细胞免疫及免疫器官的影响.成都中医药大学学报,1996(02).
[13]吴玲霓,等.肾虚、脾虚造型动物免疫超微结构的比较研究.中医药研究,1999(03).
[14]武文斌,张文信,王锦丽,王玉芳,马秀伟,T淋巴细胞亚群与肾气盛衰规律的探讨.辽宁中医杂志,1995(06).
[15]李庆阳,郑家铿,老年肾虚与T细胞亚群关系.福建中医学院学报,2001(02).
[16]张家玮,金匮肾气丸对金匮肾气丸证患者T淋巴细胞亚群的影响.北京中医,2002(01).
[]7]杨嘉珍,肾虚血瘀证与红细胞免疫的关系.湖北中医杂志,1996(03).
[18]Siegel,I., T.L. Liu, and N. Gleicher, The red-cell immune system. Lancet,1981.2(8246): 556-559
[19]陈小峰,许少锋,肾虚患者的细胞因子研究.福建中医学院学报,2000(02).
[20]徐文流,周联,肾虚与脾虚模型动物IL-1的比较.广州中医药大学学报,1997(03).
[21]李文静,陈如泉,半硫丸对甲状腺机能减退肾阳虚大鼠血清SIL-2R水平影响的实验研究.辽宁中医学院学报,2002(01).
[22]宋淑霞,等.益气补肾方药对肾虚小鼠细胞因子1L-1、IL-2及lL-12基因表达的影响.中国实验动物学报,2002(02).
[23]宋淑霞,吕占军,刘福英,益气补肾方药对肾虚小鼠脾细胞CD40、CD40L:表达的调节.中华老年医学杂志,2002(05).
[24]李承军,等.老年虚证自由基代谢机理的研究.中医杂志,1988(12).
[25]薛红丽,et al.,补肾活血延缓衰老作用的实验研究.江苏中医,1999(09).
[26]陈玉碧,郭赛珊,张宏,肾虚血瘀Ⅱ型糖尿病患者红细胞SOD、血清LPO水平的观察.北京中医,1995(04).
[27]李庆阳,江明,严桂珍,老年脾肾虚证LPO、SOD、血脂及细胞免疫水平变化.福建中医学院学报,2001(03).
[28]镇而康.关于衰老与抗衰老的现代研究.国外医学,社会医学分册,2000,(24)：97
[29]黄柄山,李爱中,范隆昌,等.肝郁气滞证及其实质研究.黑龙江中医药,1998,8(3)：4
[30]李峰,杨维益.从中医学看肝脏调节应激反应的作用,北京中医药大学学报,1998,21(1)：20
[31]陈家旭。肝脏实质的研究概.浙江中医学院学报1993,17(3)：50
[32]王朝勋.怒伤肝与神经-内分泌-免疫系统失调探析.辽宁中医杂志,1997,(24)：205
[331杜艳军,康玉屏.浅析肝脾肾在衰老中的机制.江苏中医药,2003,24(11)：6-8
[34]靳晓明,董琳,范峰,等.女贞子化学成分与药理作用的研究进展.中医药信息,2008,25 (1)：40-42
[35]张振明,葛斌,许爱霞等.女贞子多糖的抗衰老作用.中国药理学与毒理学杂志,2006,20(2)：108-111
[36]黄泰康.常用中药成分与药理手册.北京：中国医药科技出版社,1994.1806-1808
[37]张金生,郭倩明.旱莲草化学成分研究.药学学报,2001,36(1)：34-37
[38]李弋,周 琳,杨风云.旱莲草对D2半乳糖所致亚急性衰老小鼠的抗衰老作用研究.山西医科大学学报,2005,36(5)：574-576
[39]王淑梅,王灿岭.二至丸对亚急性衰老模型小鼠抗衰老作用的实验研究.中医研究,2006,19(5)：21-22.
[40]赵雪莹,李胜志,李冀.二至丸对衰老大鼠血液流变学影响的实验研究.辽宁中医杂志,2008,35(6)：945-946.
[41]孙洪涛.二至丸对衰老小鼠模型脑细胞N a+-K+-ATP酶、C a2+-ATP酶活性影响的研究.中外医疗,2008(13)：78.
[42]李弋,杨友谊.中药二至丸对老年痴呆模型小鼠脑组织N a+-K+-ATPase、Ca2+-ATPase活性及学习记忆的影响.广州医学院学报,2005,33(3)：23-25.
[43]刘大基,刘解生,徐继勋,等.二至丸对小鼠淋巴细胞免疫功能的调节作用.湖北中医杂志,2002,24(2)：48-49.
[44]操红缨,梁颂名,荣向路,等.二至丸对阴虚模型神经内分泌免疫网络调节作用的研究.中药材,2000,23(3)：164-166.
[45]高会丽,王丹巧,汪晓燕.二至丸抗衰老大鼠神经细胞凋亡的实验研究.
[46]颜德馨.气血与衰老.江苏中医,1990,(4)：27
[47]韩明向.“虚-瘀-衰老”模式初探.安徽中医学院学报,1992,11(3)：2
[48]颜德馨.中国历代中医抗衰老秘要.文汇出版社,1993
[49]颜德馨。气虚血瘀是人体衰老的主要机制.中国医药学报,1989,2：10-12
[50]韩明向.老年虚证与SOD及中药提高SOD活性的研究.安徽中医学院学报,1991,10(4)：64
[51]王香婷,朱晓红,魏民等.补气活血方药对衰老性急性肺损伤大鼠SOD及MDA的影响.中国中医基础医学杂志.2009,15(6)：435-436
[52]毛腾敏.丹参、当归对老年大鼠血瘀的影响.中西医结合杂志,1988,8(10)：635
[53]詹小萍,孙梅,金晓滢等.益肾活血方对家兔血瘀模型纤溶指标与血液流变学影响的研究.中国中药杂志,2006,31(5)：411-413
[54]刘礼意.益气活血方对老年大鼠神经免疫调节影响的研究.中国中西医结合杂志,1997,17(10)：616
[55]黄华永,沈海星,郑锦鸿.阿魏酸及其类似物的合成及其清除自由基活性研究.中国新药杂志,2006(6)：236-237
[56]徐升强,贾岷.川芎嗪对急性胰腺炎大鼠细胞凋亡的影响.微循环学杂志,2009,19(2)：25-28
[57]胡燕月,阮琴,徐叶芬等.川芎嗪和阿魏酸对大鼠离体心脏血流动力学的影响.浙江师范大学学报(自然科学版),2004,4(3)：382-385.
[58]杨静,雷燕,崔巍等.人参三七川芎提取物延缓内皮细胞复制性衰老的机制研究.中国中药杂志,2009,34(12)：1544-1548
[59]董晓华,张丹参,武海霞,衰老动物模型的研究进展及评价.河北北方学院学报,2004(06).
[60]Frisard, M. and E. Ravussin, Energy metabolism and oxidative stress:impact on the metabolic syndrome and the aging process. Endocrine,2006.29(1):p.27-32.
[61]马宏,张宗玉,童坦君,衰老的生物学标志.生理科学进展,2002(01).
[62]Sohal, R.S. and R. Weindruch, Oxidative stress, caloric restriction, and aging. Science,1996. 273(5271):59-63.
[63]Ozanne, S.E. and C.N. Hales, Lifespan:catch-up growth and obesity in male mice. Nature, 2004.427(6973):p.411-2.
[64]Mair, W., et al., Demography of dietary restriction and death in Drosophila. Science,2003. 301 (5640):1731-1733
[65]Masoro, E.J., Overview of caloric restriction and ageing. Mech Ageing Dev,2005.126(9): 913-22.
[66]沈自尹,淫羊藿总黄酮延缓衰老的研究.世界科学技术-中医药现代化,2005(01).
[67]黎志萍,赵伟康,徐品初,等.益气活血方药对老年大鼠肝脏衰老相关基因表达的影响,中西医结合学报,2005,3(5)：370-373
[68]周明学,徐浩,潘琳,等.活血、益气、化痰中药对ApoE基因敲除小鼠主动脉粥样硬化斑块炎症反应的影响.中国中医急症,2008,17(4)：496-498
[69]杨靖,詹向红,孙哗,等.四君子汤对D2半乳糖衰老模型小鼠心、肝、脑组织MDA含量及端粒酶活性的影响,中国中西医结合杂志,2005,25(6)：531-533
[70]Erik M. Jorgensen and Susan E.Mango. The art and desige of genetic screens:caenorhabditis elegans. Nature Reviews Genetics.2002,3,356-369
[71]Sulston,J.E.,Horvitz,H.R.Post-embryonic cell lineages of the nematode Caenorhabditiselegans. Dev. Biol.1997,56,110-156
[72]Bargmann CI. Neurobioligy of the Caenorhabditis elegans genome. Science,1998.282: 2028-2033
[73]Vanfleteren, J.R., Braeckman, B.P.. Mechanisms of life span determination in Caenorhabditis elegans. Neurobiol. Aging,1999,20,487-502.
[74]Hobert, O., Behavioral plasticity in C.elegans:Paradigms, circuits, genes. J Neurobiol.2003, 54(1):203-223
[75]Harriet Gershon, David Gershon. Caenorhabditis elegans-a paradigm for aging research: advantages and limitations. Mechanisms of Ageing and Development,2002,123:261-274
[76]蔡外娇,张新民,黄建华,等.淫羊藿总黄酮延缓秀丽隐杆线虫衰老的实验研究,中国中西医结合杂志,2008,28(6)：522-525
[77]Mark A. Wilson, Barbara Shukitt-Hale, Wilhelmina Kalt, et al. Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans, Aging Cell,2006,5,59-68
[78]Brenner, S. The genetics of Caenorhabditis elegans. Genetics,1974,77:71-94
[79]Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-△ △Ct method. Methods,2001,25:402-408
[80]李春生,侯荣先.国内应用寿命试验和衰老动物模型研究抗衰老中药的近室内概况.中医杂志,1998；39(11)：690-693
[81]Evason K, Huang C, Yamben I, et al. Anticonvulsant medications extend worm life-span. Science,2005,307 (12):258-62
[82]冀敦福,季海刚.关于衰老与老年病中医机制的探讨.天津中医学院学报,2004,23(4)：169
[83]于英军,管宇,宋高臣.蜂胶对果蝇寿命的影响,中医药学报,2004,32(5)：53-54
[84]Partridge, L. et al. Sex and death:what is the connection? Cell,2005,120,461-472
[85]Mukhopadhyay A, Tissenbaum HA. Reproduction and longevity:secrets revealed by C.elegans. Trands Cell Biol,2007,17(2):65-71
[86]Kenyon C. The plasticity of aging:insights from long-lived mutants. Cell,2005,120 (4): 449-460
[87]Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science,2003,299(5611):1346-1351
[88]Browner, W.S., et al., The genetics of human longevity. American Journal of Medicine,2004. 117(11):p.851-860
[89]Braeckman B. P., Vanfleteren J. R. Genetic control of longevity in C. elegans. Experimental Gerontology,2007,42:90-98
[90]Ailion, M., T. Inoue, C. I. Weaver, R. W. Holdcraft, et al. Neurosecretory control of aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA,1999,96:7394-7397.
[91]Manuel J. Munoz, Donald L. Riddle. Positive Selection of Caenorhabditis elegans Mutants With Increased Stress Resistance and Longevity. Genetics,2003,163:171-180
[92]Adam Antebi. Genetics of Aging in Caenorhabditis elegans. PLoS Genetics,2007,3(9):1565-1571
[93]Hristova M, Birse D, Hong Y, Ambros V. The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding. Mol Cell Biol.2005,25:11059-11072.
[94]马永兴,俞卓伟主编.现代衰老学,2008,p496
[95]Bernard Lakowski, Siegfried Hekimi. Determination of life-span in caenorhabditis elegans by four clock genes. Science,1996,272:1010-1013
[96]Chang-Su Lim, I. Saira Mian, Abby F. Dernburg,et al. C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p.
[97]Lemieux, J., Lakowski, B., Webb, A.,et al. Regulation of physiological rates in Current Biology,2001,11:1706-1710 Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria. Genetics, 2001,159,147-157.
[98]Bart P. Braeckman, Koen Houthoofd, Annemie De Vreese,et al. Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans. Current Biology 1999,9(9):493-496
[99]林水森,周如倩.中医论衰老机理,上海中医药杂志,1994,12：14-16
[100]王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报,2002,2002,26(4)：249
[101]吴小明,朱美香,李如辉.肝肾二脏与抗衰老的关系探讨.甘肃中医,2004,17(3)：3-6
[102]陆秀兰.生物钟与衰老.辽宁中医杂志,1998,25(11)：509-511
[103]顾佳黎,吴,涛,童红飞,等.生物钟与衰老的相关研究进展.生理科学进展,2009,40(2)：123-128
[104]颜德馨.中国历代中医抗衰老秘要.文汇出版社,1993
[105]刘士豪.塞里应激学概要.上海：上海科学技术出版社,1963,21
[106]Selye H. Stress and aging. J Am Ger Soci,1970,18:669-679
[107]Tissieres A, Mitchell H K, Tracy U M. Protein synthesis in salivary glands of Drosophila melanogaster in relation to chromosome puffs. J. Mol. Biol.1974,84:389-398
[108]孙秀兰.从自由基角度研究应激与衰老的关系.中国行为医学科学,1998,7(1)：73-76
[109]Lithgow GJ, Walker GA. Stress resistance as a determinate of C.elegans lifespan. Mech Ageing Dev,2002,123(7):765-771
[110]Tsui D,van der Kooy D.Serotonin mediates a learned increase in attraction to high concentrations of benzaldehyde in aged C. elegans. Learning & Memory.2008 Oct 30; 15(11):844-855
[111]Pierce SB, Costa M, Wisotzkey R,et al. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. GeneDevelopment.2001,15(6):672-686
[112]Tissenbaum, H.A., Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature.2001,410,227-230
[113]Yoko Honda,Shuji Honda. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. The FASEB Journal.1999,13:1385-1393
[114]Manoj Nanji, Neil A. Hopper, David Gems. LET-60 RAS modulates effects of insulin/IGF-1 signaling on development and aging in Caenorhabditis elegans. Aging Cell.2005,4,235-245
[115]Masoro EJ.Overview of caloric restriction and ageing. Mechanism of Aging and Development,2005,126:913-922
[116]Guarente L, Picard F. Calorie restriction2the SIR2 connection.Cell,2005,120 (4):473-482
[117]Tissenbaum, H.A., Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature.2001,410,227-230.
[118]Vellai T, Takacs-Vellai K, Zhang Y, et al. Genetics:influence of TOR kinase on lifespan in C. elegans. Nature,2003,426:620
[119]Kailiang Jia, Di Chen, Donald L. Riddle. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development.2004,131,3897-3906
[120]刘小雨,王琦,夏世金,等.增龄进程淋巴细胞核转录因子κB相关基因表达及淫羊藿总黄酮的调控作用.中医杂志,2009,50(1)：66-68
[121]Jennifer M. A. Tullet, Maren Hertweck, Jae Hyung An,etc. Direct inhibition of the longevity promoting factor SKN-1 by Insulin-like signaling in C. elegans. Cell.2008 March 21; 132(6):1025-1038.
[122]Bishop NA, Guarente L. Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature,2007,447 (7144):545-549
[123]Kiang JG, Tsokos G. Heat Shock Protein 70 kDa:Molecular Biology, Biochemistry, and Physiology. Pharmacol Ther,1998,80:183-201
[124]Caminsi A, Diez-fernandez C, Prieto P. Cell Expression of Heat Shock Proteins in Dog Neutrophils after Oxidative Stress. Toxicology in Vitro,1000,13:437-443
[125]Morita K, Saito T, Ohta M, et al. Expression analysis of psychological stress-associated genes in peripheral blood leukocytes. Neuroscience Letters,2005,381:57-62
[126]Oehler R, Pusch E, Zellner M, et al. Cell type-specific variations in the induction of hsp70 in human leukocytes by feverlike whole body hyperthermia. Cell Stress Chaperones,2001,6: 306-315
[127]王玮文,邵枫,刘美,等.衰老、慢性应激与免疫细胞热休克蛋白70反应抑制.中国行为医学科学,2007,16(10)：951-953
[128]马永兴,俞卓伟主编.现代衰老学,2008,141
[129]Vijg J, Suh Y. Functional Genomics of Ageing. Mechanisms of Ageing and Development, 2003,124:3-8
[130]马永兴,俞卓伟主编.现代衰老学,2008,1345-1350
[131]陈方敏,赵伟康,徐品初,等.补肾、健脾、益气、活血法对衰老细胞周期基因表达的调控作用.中国中西医结合杂志,2003,23(11)：837-840