“衰老基因”与“长寿基因”

“衰老基因”与“长寿基因”童坦君,张宗玉（北京医科大学生物化学与分子生物学系,北京１０００８３）关键词衰老基因,长寿基因衰老过程存在着遗传程序控制,这一看法确有证据。至于生物体内是否存在专门引起衰老的“衰老基因”或专使寿命延长的“长寿基因”,近年来也...     

人类长寿相关基因研究进展

人类长寿是多因素、系统性生物学现象。衰老死亡是不可抗拒的自然规律,但通过科学研究可以延缓衰老达到延长寿命目的。影响长寿的因素可分为遗传和环境两种,其中遗传因素是决定长寿的内因,而环境因素则作为影响长寿的外因。本文介绍了人类长寿研究领域的研究现状和进展,概括人类长寿相关基因研究中取得的成果,并将人类染色体长寿相关基因归纳为三类,分别是控制炎症和代谢的长寿相关基因,以及控制信号通路的长寿相关基因,并进一步对三类基因中的代表性基因进行介绍。同时,对长寿研究的方向与未来提出了展望。     

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。     

浅谈长寿信号通路及它们在不同组织间的传递

衰老受着众多信号通路的调节。对于多细胞生物,这些衰老相关信号不仅在细胞内进行传递,更在细胞组织间进行通讯。该文拟结合几条具体的长寿信号通路,综述长寿信号在跨越组织协调全身衰老进程的机制。     

HLA与长寿及寿限关系的初步观察—附超氧化物歧化酶(SOD）检查结果

目前一般认为,衰老与长寿的机理是受综 合性而非单一因素的影响,其中遗传是一个公 认的重要或主要因素〔7,9,12,15,161。研究各种族或各 地区人体白细胞抗原（HLA）与长寿老人（>90 岁）的关系,有可能对衰老与遗传的关系提供 有价值的资料及进一步研究的线索。国外对 HLA与衰老及寿限的关系尚无一致的意见[5,810 鉴于遗传可能仅在极端长寿对象中方可显示其 对寿限的效应‘,,, 选择长寿老人作为观察对象 可能较为适当[141。国外应用长寿老人作HLA 与寿限相关性的探讨,只在近年有少数资 料17,8,10,141,国内尚未见到这方面的报道。我们 于1983年检查了50例长寿老人,8例高龄老 人（80-89岁）的HLA 分型,并与210例2 0- 知岁组对照比较,同时用化学比色法测定红细 胞超氧化物歧化酶(Superoxide Dismutase, SOD) 含量及其他有关检查。兹将结果分析讨论如 下。     

综述: 衰老及相关疾病细胞分子机制研究进展

人类及其他生物随时间推移逐渐发生细胞功能丧失,即细胞衰老.这个过程如突显在某个组织器官,则可引起这个组织和器官的衰老性疾病.然而,最近的研究表明,哺乳动物在出生之前胚胎发育的生理条件下,即已经出现细胞和组织的复制性衰老现象.机制研究显示多种分子从细胞(核)内外引起生理性和应激性细胞复制性衰老.而自然界中某些生物随时间推移生命力增强、并不发生衰老.这些现象的分子机制,还有如发生在脑及代谢性疾病中的非复制性细胞衰老等,都还是个谜.本文就近期衰老的机制、细胞衰老的类型以及某些衰老相关疾病的分子基础的最新研究进展做一个扼要综述.论文包含以下几个部分:a.细胞衰老的定义、分类和机制;b.生理性衰老:发育中程序化衰老;c.内环境稳态与组织器官衰老;d.一型细胞复制性衰老及相关疾病:端粒长度与预测衰老及肿瘤预后、特发性肺纤维化、高血压;e.二型非复制性细胞衰老及相关疾病:帕金森病、糖尿病;f.衰老与长寿的物种多样性.     

衰老及相关疾病细胞分子机制研究进展

人类及其他生物随时间推移逐渐发生细胞功能丧失,即细胞衰老.这个过程如突显在某个组织器官,则可引起这个组织和器官的衰老性疾病.然而,最近的研究表明,哺乳动物在出生之前胚胎发育的生理条件下,即已经出现细胞和组织的复制性衰老现象.机制研究显示多种分子从细胞(核)内外引起生理性和应激性细胞复制性衰老.而自然界中某些生物随时间推移生命力增强、并不发生衰老.这些现象的分子机制,还有如发生在脑及代谢性疾病中的非复制性细胞衰老等,都还是个谜.本文就近期衰老的机制、细胞衰老的类型以及某些衰老相关疾病的分子基础的最新研究进展做一个扼要综述.论文包含以下几个部分:a.细胞衰老的定义、分类和机制;b.生理性衰老:发育中程序化衰老;c.内环境稳态与组织器官衰老;d.一型细胞复制性衰老及相关疾病:端粒长度与预测衰老及肿瘤预后、特发性肺纤维化、高血压;e.二型非复制性细胞衰老及相关疾病:帕金森病、糖尿病;f.衰老与长寿的物种多样性.     

人类基因组扫描发现4号染色体长寿相关位点

多数百岁人晚年都很健康 .心肌病、中风、糖尿病、癌及老年痴呆等老年病出现很晚或根本不出现 .Ａｎｎｉ ｂａｌｅ等假设 ,百岁老人比普通人衰老慢 .他们发现 ,百岁老人的同胞 (ｓｉｂｓｈｉｐｓ)活过 91岁的几率高于对照 4倍 .于是 ,以研究长寿同胞组为手段 ,寻找长寿的遗传因素或利于长寿的环境因素 .在筛查中他们发现 ,4个格外长寿的家族 ,支持了长寿的遗传因素说 .Ａｎｎｉｂａｌｅ等研究的对象包括 143个长寿同胞组和 32 2个长寿个体 .删除显著偏离孟德尔遗传规律的几个家系和个体后 ,实际研究了年龄 91— 10 9岁长寿老人 137个同胞组 …     

mTOR信号通路与衰老及衰老相关重大疾病

衰老引起多器官功能衰减,导致各种衰老相关代谢、心血管重大疾病发生和发展.哺乳动物雷帕霉素靶蛋白/雷帕霉素机能靶蛋白(mammalian/mechanistic target of rapamycin,mTOR)信号通路作为生长、发育、代谢、免疫、癌症等生理活动的主要调控者,通过影响细胞自噬、内质网应激、线粒体等形成复杂调控网络,在衰老与长寿中发挥关键作用.mTOR信号通路与许多衰老相关重大疾病(如代谢综合征、心血管疾病、神经退行性病变、肿瘤等)的发生发展密切相关,故以mTOR为靶点的药物开发与应用是未来延缓衰老及治疗衰老相关疾病的热点之一.     

综述: mTOR信号通路与衰老及衰老相关重大疾病

衰老引起多器官功能衰减,导致各种衰老相关代谢、心血管重大疾病发生和发展.哺乳动物雷帕霉素靶蛋白/雷帕霉素机能靶蛋白(mammalian/mechanistic target of rapamycin,mTOR)信号通路作为生长、发育、代谢、免疫、癌症等生理活动的主要调控者,通过影响细胞自噬、内质网应激、线粒体等形成复杂调控网络,在衰老与长寿中发挥关键作用.mTOR信号通路与许多衰老相关重大疾病(如代谢综合征、心血管疾病、神经退行性病变、肿瘤等)的发生发展密切相关,故以mTOR为靶点的药物开发与应用是未来延缓衰老及治疗衰老相关疾病的热点之一.     

Garden ant homing behavior in a maze task based on local visual cues

Although it has been shown that visual cues play an essential role in navigation by the garden ant Lasius niger, no previous studies have addressed the way in which information from local visual cues is acquired and utilized in navigation. We found that in the absence of pheromone trails, ants whose homing motivation was triggered by feeding returned to the nest following local visual cues. In our experiments, the ants travelled through a maze to reach a feeder. They explored the maze and sometimes became trapped in its dead ends. We found that the ants more effectively used visual cues during their homeward journey if they experienced a dead end during their outward journey. This result suggested that the ants used the information acquired from visual cues during the outward journey to avoid a dead end on their return journey.     

Dead reckoning in a small mammal: the evaluation of distance

When hoarding food under infra-red light, golden hamsters Mesocricetus auratus W. return fairly directly from a feeding place to their nest site by evaluating and updating internal signals that they have generated during the previous outward journey to the feeding place. To test more specifically the animals' capacity to evaluate the linear components of the outward journey, the subjects were led from their (cone-shaped) nest to a feeding place along a detour which comprised either 2 (experiment 1) or 5 (experiment 2) segments; adjoining segments were at right angles to each other. In these conditions, the subjects remained significantly oriented towards the nest and therefore were capable of assessing translations as well as rotations during the outward journey. In experiment 3, the nest was removed after the hamsters had started the direct outward journey to the feeding place and the hamsters were rotated during the food uptake. The animals were no longer oriented towards the starting point of their journey, but nonetheless covered, along a fairly straight path, the correct homing distance, and then changed over to a circular search path. These results confirm that mammals can derive the linear components of an outward journey from self-generated signals and therefore are able to judge the homing distance without relying on cues from the environment. For a number of detour outward journeys, our data yield an unexpectedly good fit to Müller and Wehner's (1988) model of dead reckoning in ants. However, this is no longer the case when the outward journey contains an initial loop which brings the subject back to the starting point. These findings are discussed in terms of the biological significance and limitations of an approximate form of path integration.     

How desert ants cope with enforced detours on their way home

Summary We ask whether desert ants (Cataglyphis fortis) perform path integration on their homeward as well as on their outward journey. If path integration does occur on the return journey, then, after an enforced detour, the ant's trajectory should point directly at its nest. To test whether this is so, ants were trained to forage at a spot 25 m from their nest. As an ant began its return journey to the nest, it was caught and transported to a test area where it was released either 2 m or 12 m from a wide barrier which obstructed its homeward path. The direction of the ants' trajectory after detouring around the barrier corresponded closely to that predicted on the assumption that the home vector is accurately updated during the detour.     

Time Making and Place Making: A Journey of Immigration from Ethiopia to Israel

ABSTRACT

Anthropological studies of immigration usually focus on the immigrants’ country of origin or their destination. The present ethnographic study is a claim that the immigration experience must be examined as part of a journey and movement. The study was designed to show how the immigration process of Zera Beita Israel (Feres Mura) from Ethiopia to Israel is constructed on a process of journey and dialogue among the various stations. The two main aspects of the journey are place making – constructing a place in the unique context of immigration, and time making – creating being-time and meta-time, both unique to immigration. Each of the places affects the immigration process and is affected by this dynamic, nonlinear process. The combined concepts of place making and immigration time help explain the complexity of immigration.     

A long and winding road: the Plasmodium sporozoite's journey in the mammalian host

The Plasmodium sporozoite, the infectious stage of the malaria parasite, makes a remarkable journey in its mammalian host. Here we review our current knowledge of the molecular and cellular basis of this journey, which begins in the skin and ends in the hepatocyte.     

Journeying Between Desire and Anthropology: A Story in Suspense

Anthropology is a discipline based on the motif of the journey and ‘the myth of the eternal return’. This is the journey out to the ‘other’in order to return to constitute ‘self, and this movement is a movement of desire. The desire is for wholeness, for self‐presence, for a unified self. It is a desire for origins. And this desire is evident in anthropological practices as it is in myths and fairytales—all tell stories that speak of the desire for a separate, an original, self. Yet ‘the myth of the eternal return’reveals that the enactment of the story is itself originating. The origin is not a thing to be hunted down and appropriated—it is no thing. Like the archetypes which flow through stories, it is alive in the telling. The story I tell in this paper is about my own desires. It speaks of the desire to undergo the rite of passage of anthropology, and of how this journey was interrupted by the anthropologist who always journeys before me. And yet. it is through the inextricable relations with the writings of the “other‘ anthropologist that alluring moments of different desiring are fleetingly revealed. In the end. my relations with anthropology tell of a paradox: of the desire for a transcendental journey in order to constitute self and the seductive desire for immersion—to lose self, the story remains in suspense.     

Going with the flow: a brief history of the study of the honeybee’s navigational ‘odometer’

Honeybees navigate to a food source using a sky-based compass to determine their travel direction, and an odometer to register how far they have travelled. The past 20 years have seen a renewed interest in understanding the nature of the odometer. Early work, pioneered by von Frisch and colleagues, hypothesized that travel distance is measured in terms of the energy that is consumed during the journey. More recent studies suggest that visual cues play a role as well. Specifically, bees appear to gauge travel distance by sensing the extent to which the image of the environment moves in the eye during the journey from the hive to the food source. Most of the evidence indicates that travel distance is measured during the outbound journey. Accumulation of odometric errors is restricted by resetting the odometer every time a prominent landmark is passed. When making detours around large obstacles, the odometer registers the total distance of the path that is flown to the destination, and not the “bee-line” distance. Finally, recent studies are revealing that bees can perform odometry in three dimensions.     

Host factors exploited by retroviruses

Retroviruses make a long and complex journey from outside the cell to the nucleus in the early stages of infection, and then an equally long journey back out again in the late stages of infection. Ongoing efforts are identifying an enormous array of cellular proteins that are used by the viruses in the course of their travels. These host factors are potential new targets for therapeutic intervention.     

A journey from reductionist to systemic cell biology aboard the schooner Tara

In this essay I describe my personal journey from reductionist to systems cell biology and describe how this in turn led to a 3-year sea voyage to explore complex ocean communities. In describing this journey, I hope to convey some important principles that I gleaned along the way. I realized that cellular functions emerge from multiple molecular interactions and that new approaches borrowed from statistical physics are required to understand the emergence of such complex systems. Then I wondered how such interaction networks developed during evolution. Because life first evolved in the oceans, it became a natural thing to start looking at the small organisms that compose the plankton in the world's oceans, of which 98% are … individual cells-hence the Tara Oceans voyage, which finished on 31 March 2012 in Lorient, France, after a 60,000-mile around-the-world journey that collected more than 30,000 samples from 153 sampling stations.