D－半乳糖致衰老小鼠与幼龄小鼠的垂体差异蛋白质分析

脑垂体是控制动物生长发育衰老死亡非常重要的一个器官.随着机体的衰老,垂体功能退化是必然趋势.D 半乳糖致衰老模型已被广泛用于研究衰老机制和筛选药物靶标,然而其分子机制尚未清楚.本研究采用差异蛋白质组学方法,以寻找D 半乳糖致衰老小鼠和幼龄小鼠垂体的差异蛋白质,为弄清其功能障碍的分子机制提供新的研究方法和线索.基于双相电泳和质谱结合的方法,本研究发现了46个大于2倍的差异蛋白质,其中32个得到可靠的鉴定（P <005）. 对差异蛋白质功能分析发现, 这些显著差异蛋白质主要分布于糖代谢通路,可能与线粒体功能紊乱有关.我们的研究数据为更好地理解D 半乳糖致衰老小鼠垂体功能障碍的内在机制提供了线索.     

衰老及相关基因群

综述20世纪与基因相关的衰老原理的探索及其进展,整体动物水平的衰老研究归纳了衰老了诸多表象但疏于对衰老本质的探讨。线粒体－自由基衰老学说阐述了线粒体DNA的损伤与衰老有很大的相关性,由Hayflic k分裂限制衍生的端粒衰老学说给衰老机制提供了重要信息,目前狭隘的基因程序化衰老学说已和损伤衰老概念有机的联系在了一起。总之,自由基衰老学说得到了氧化衰老学说和糖基化衰老学说的补充逐渐形成了生化副反应与基因衰老学说的大统一衰老机制板块理论。     

长寿和衰老基因及相关基因研究进展

简要介绍了长寿和衰老基因及相关基因在酵母、线虫、果蝇和哺乳动物中的最新遗传学研究进展；概述了“生物钟”、端粒和端粒酶在人类长寿和衰老进程中的重要作用。相信随着人类遗传学和分子生物学研究的深入，将有更多的长寿和衰老基因及相关基因被发现，为揭示衰老机制和延年益寿提供依据。     

基于Cytoscape下斑马鱼衰老基因-蛋白质的模块化分析

近20年来,斑马鱼逐渐成为研究人类基因功能的重要模型动物。同时,通过对斑马鱼参考基因组序列和10 000多个蛋白编码基因的鉴定,表明斑马鱼至少与人类基因有75%的同源性,进一步验证了斑马鱼基因组序列可以作为衰老的研究模型。此外,其良好保守的分子和细胞生理学的广泛特征使斑马鱼成为揭示衰老、疾病和修复的潜在机制的极好模型。但是斑马鱼衰老的分子机制很少发生分子间的相互作用,因此蛋白质-蛋白相互作用(PPI)网络是非常可取的。本实验描述了斑马鱼这种生物衰老机制的模型,其涵盖了与衰老相关的87种蛋白质之间的767种相互作用。这不仅包含准确预测的PPI,还包含从文献收集以及实验所得的那些分子相互作用。同时,将这些分子相互作用模块化,形成模块化,找到11个中心基因,分析预测其衰老过程。希望能帮助研究斑马鱼的学者研究其衰老过程,提供一些假说和帮助。     

主要干性基因与衰老相关基因表达水平的相互拮抗关系

目前广泛地利用传统的体细胞衰老理论和方法对成体干细胞衰老进行研究,忽视了成体干细胞特有的自我更新功能和相应的干性基因的作用.干性基因的下调可能是导致间充质干细胞衰老的主要原因.通过查阅相关资料发现主要干性基因与衰老相关基因表达水平的相互拮抗关系,这体现在以下4个方面:a.干细胞衰老伴随着干性基因的下调;b.干性基因表达抑制细胞的衰老;c.干性基因抑制衰老相关基因的表达;d.抑制衰老相关基因促进干性基因的表达.干性基因与衰老相关基因的表达水平存在相互拮抗关系,这为成体干细胞衰老可能源于成体干细胞的干性降低的观点提供了坚实的分子基础.     

脑细胞的基因及其表达与衰老

概述了脑与衰老在神经分子生物学方面的研究进展 ,包括 :细胞衰老分子机制的主要进展 ,衰老脑在基因及其表达水平的研究进展 ;阿尔茨海默病 (AlzheimerDisease ,AD)相关基因研究进展 ,帕金森病 (porkinsondisease ,PD)相关基因研究进展[7] 。这些研究成果对脑与衰老的关系、对脑在基因及其表达水平上衰老机制认识的加深乃至对衰老脑的基因治疗均具有理论意义和应用价值。     

紫花针茅WRKY53基因的克隆、序列分析及功能鉴定

植物WRKY转录因子家族在叶片衰老中起着重要的调节作用,其成员WRKY53基因与叶片衰老密切相关。本文利用紫花针茅(Stipa purpurea Griseb.)的一条EST序列,克隆获得Sp WRKY53基因的全长CDS序列,其开放阅读框为1443 bp,编码480个氨基酸,蛋白质分子量为50.9 k D,理论等电点为7.64。序列比对结果和系统进化分析表明,Sp WRKY53基因有2个WRKY序列,与已报道的小麦(Triticum aestivem L.)的WRKY53基因结构相似。亚细胞定位结果显示该蛋白定位于细胞核上。紫花针茅WRKY53基因的过表达以及表达分析表明,该基因能够加速植物叶片衰老并在多种非生物胁迫下上调表达。本研究为WRKY53基因在牧草分子育种中的进一步研究奠定了基础。     

染色体外DNA在酵母细胞衰老中的作用

细胞衰老的影响因素甚多,机制复杂。近年来已发现酵母染色体外ＤＮＡ在细胞衰老中具有重要作用,并认为细胞的衰老受控于一种特定的染色体外ＤＮＡ复制的次数,具有精确的时间控制机制［１、２］。１．染色体外ＤＮＡ与衰老的关系酵母染色体外存在大小不等的ｒＤＮＡ环,称为染色体外ｒＤＮＡ环（ｅｘｔｒａｃｈｒｏｍｏ－ｓｏｍａｌｒＤＮＡｃｉｒｃｌｅ,ＥＲＣ）。已发现衰老的酵母细胞中含有丰富的ＥＲＣ,而年轻酵母细胞中的ＥＲＣ则很少。芽殖酵母中含有人类Ｗｅｒｎｅｒ氏综合征（一种早老症）ＷＲＮ基因的同源序列——ＳＧＳ１基因…     

叶片衰老过程中的蛋白激酶和蛋白磷酸酶

衰老是受遗传程序严格控制的植物个体发育过程中的一个必经阶段,由特殊发育信号通过一定的信号传导路径来启动和控制。研究发现,蛋白激酶和蛋白磷酸酶所介导的可逆磷酸化反应在叶片衰老信号传递和衰老的启动和进程控制过程中发挥了重要作用。本文对近年参与叶片衰老调控的蛋白激酶和蛋白磷酸酶基因的分离鉴定及功能研究进行了综述。     

果实成熟衰老过程中蛋白质组学研究进展

蛋白质组学已开始应用于果实成熟衰老研究,以明确蛋白差异表达与成熟衰老的关系和深入揭示果实成熟衰老过程的分子机制。本文综述了蛋白质组学在果实成熟衰老研究中的重要性、果实样品蛋白的提取制备方法,重点介绍了蛋白质组学在果实成熟衰老机制、果实抗病性机制、冷害机制以及采后处理对果实成熟调控研究中的应用,分析了蛋白质组学在果实成熟衰老研究中存在的不足,提出了今后研究的方向。     

综述:羰基应激与衰老机理及阿尔茨海默病早期分子病因

本文从人体衰老过程中重要的共性生化过程——羰基应激——的角度出发,探讨老年性痴呆,主要指阿尔茨海默病(AD),发生发展的早期分子病因．首先,讨论与脂类、碳水化合物和蛋白质自由基氧化(氧应激)和非酶糖基化(糖应激)产生的羰基毒化作用相关的化学反应．接着,列举活性羰基在AD患者体内存在的证据并探究这些羰基毒素对细胞结构与功能的影响．最后,分析和归纳脑组织中针对羰基毒化的解毒机理,进而探讨寻找基于该机理防治AD以至抵御衰老、疲劳、亚健康的方法与途径．     

The spatial association of gene expression evolves from synchrony to asynchrony and stochasticity with age

For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging.     

Nuclear Genetic Material as an Initial Substrate of Aging in Animals

General properties of aging in animals are considered on the basis of the literature evidence and the results obtained by the authors of this paper. The existence of a specific aging mechanism is inferred. The operation of this mechanism is controlled not only by genes but also by particular noncoding genomic sequences with variable structure. The beginning of senescence in animals is determined by DNA lesions located in neural cells and probably in a minor genomic fraction. The authors refute the narrow concept of aging as a mechanism increasing the probability of death. Mortality as a continuous process occurring with the probability of 100 percent is an integral attribute of living organisms on the Earth.     

TERRA介导的端粒维持

真核细胞线状染色体末端特殊结构被称为端粒,而端粒维持对于生命体来说具有十分重要的意义,其维持机制也十分复杂.端粒酶可以通过其具有的特殊逆转录酶特性,利用自身的RNA模板(TERC)以及具有催化功能的蛋白质亚基(TERT)延长端粒,维持其长度.本文着重综述端粒TERRA (telomeric repeat-containing RNA)对端粒维持的影响及其作用机制.首先介绍端粒维持与细胞存活老化之间的关系;其次,阐述TERRA的结构及其转录特性,TERRA依赖的DNA∶RNA杂合体和R-loop形成和结构特点,TERRA结合蛋白及其作用;进而讨论依赖于TERRA的端粒维护分子机制以及在生命过程中的意义.     

Non-neutral role of replicative senescence in tissue homeostasis and tumorigenesis

Normal somatic cells divide only a limited number of times reaching a state known as replicative senescence. This restraint in reproductive potential has been proposed as a mechanism evolved in higher eukaryotes to protect the organism from developing cancer. However, despite this protection there is a positive correlation between tumor incidence and organism aging when cells are potentially closer to their replication limit. We use simple mathematical models derived from quasispecies theory to analyse the role of senescence in various scenarios with different cell types according to their replicative capacity. The models predict that a situation with cells launching more often the senescence response plays against tissue homeostasis favoring tumor initiation. It is also shown that cancer cells arising early in organism life are more sensitive to genetic instabilities progressing less often toward tissue invasion. The passage of cells through crisis emerges as a mechanism to maintain tissue homeostasis that is weakened in aged individuals. The models introduced, though simple, help to integrate experimental information relating tumorigenesis with cellular and organism aging phenomena.     

端粒维持研究进展

端粒是现代生物学的研究热点,与肿瘤发生、基因表达调控、衰老有着密切的关系。本综述介绍当前对端粒维持机理研究的进展。在端粒维持过程中有两类重要的蛋白：端粒相关蛋白和端粒酶。端粒相关蛋白是直接或间接与端粒结合的蛋白 ,在维持端粒稳定性方面有重要作用。端粒酶,特别是其催化亚基ｈＴＥＲＴ,在端粒延长过程中起着不可替代的作用,与细胞永生化和癌变密切相关。此外还介绍了在某些细胞中存在的不依赖端粒酶的端粒延长机     

衰老的分子机制与干预研究的最新进展

随着全球老龄化时代的到来,衰老和衰老相关疾病带来的健康问题日益突出。如何最大限度地维持老龄人口健康、干预衰老相关疾病并延缓衰老的发生对于医疗系统、科研机构乃至整个社会都是巨大的挑战。目前,对于衰老的分子机制研究已经有长足的进步,对于衰老进程的生物学和遗传学机制已有突破性的认识,对于衰老相关疾病的发病机制也有了深刻的理解。但这些研究成果还远远达不到能够延缓人类衰老并遏制衰老相关疾病的发生的要求。该文将从衰老的分子机制和干预手段这两个方面入手,综述衰老的理论研究和实际应用中的主要成果和最新进展。     

Mammal aging: Active and passive mechanisms and their medical implications

This article compares two hypotheses regarding the mechanisms responsible for aging in humans and other mammals. In the passive mechanism, aging is the result of inadequacies in maintenance and repair functions that act to prevent or repair damage from fundamental deteriorative processes. In the active mechanism, a life span management system purposely limits life span by deactivating maintenance and repair processes beyond a species-specific age.As described here, the active mechanism provides a much better fit to observational evidence while the passive mechanism provides a much better fit to traditional evolutionary mechanics theory. However, there are many other observations that conflict with traditional theory and consequently a number of alternative evolutionary mechanics theories have been developed since 1962. Several of these alternatives support active life span management and aging theories providing a rationale for active life span management have been developed based on each of those alternatives.This issue is very important to our ability to treat age-related diseases and conditions. If indeed the passive mechanism is correct, then efforts should continue to be exerted to find treatments for each different manifestation of aging, independently of the others. If the active concept is valid it is clear that there are, in addition, substantial opportunities for finding agents that generally delay aging and simultaneously ameliorate multiple manifestations of aging.In the past, the evolutionary issues have been used as essentially the entire justification for summarily rejecting active theories. Given the public health considerations and the increasing number of issues surrounding evolutionary mechanics theory, this is no longer a reasonable or responsible path.     

烟叶微生物及其在烟叶发酵和醇化中的作用研究进展

微生物在烟叶发酵和醇化过程中具有十分重要的作用。本文综述了烟叶微生物概况及其在烟叶发酵和醇化中的应用和研究进展。主要介绍了烟叶微生物的区系划分、烟叶发酵和醇化过程中微生物动态变化以及外源添加微生物的应用方法。阐述了微生物在缩短烟叶发酵和醇化周期、改善烟叶品质、降低烟叶有害物质和提高烟叶安全性等方面的研究应用成果。最后,对该领域今后的研究方向提出了展望。     

Autophagy, mitochondrial quality control, and oncogenesis

Cancer is a disease associated with aging. More than 80% of human cancers are diagnosed in people aged 55 years or older. Autophagy has recently been demonstrated to be a novel mechanism of tumor suppression. Interestingly, autophagy also plays an important role in the control of aging. Here we summarize the genetic studies of autophagy in tumorigenesis and aging, and propose that autophagy may suppress tumor development and prevent aging through a common mechanism involving mitochondrial surveillance.