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。     

泛议衰老

衰老是机体在退化时期功能下降及生理紊乱的综合表现,与机体的自由基水平,染色体端粒长度和衰老过程中起作用的重要基因有密切关系。作者重点介绍自由学说、饮食限制学说、端粒学说,以及衰老相关基因WRN、koltho和胰岛素样生长因子1（IGF－1）的信号传导途径、从遗传学的角度对衰老机理作一阐述。     

衰老与微循环学说

衰老的原因和机制至今未明 ,目前存在两大类学说 ,一类学说认为衰老是机体生活过程中发生的不可逆损伤积累的结果 ;另一类学说认为衰老是由遗传确定的一个有程序的过程 [1] 。由此可见 ,衰老是一个十分复杂的生物学过程 ,它不可能取决于某一系统 ,某一因素的作用。1　启契　　衰老的微循环学说尚未见报道。作者根据 2 0余年微循环的学习和研究 ,观察人体生、长、老、病、死的微循环变化 ,人生各个时期微循环的变化及其各自的特点 ,阅读和借鉴有关文献 ,明确微循环障碍与衰老存在着因果关系 ,微循环障碍可以是衰老的原因之一 ,亦可以是衰老的…     

大豆叶片衰老过程中质膜蛋白激酶自磷酸化状态和催化活性的变化

以大豆幼苗初生叶为材料研究了衰老过程中质膜蛋白激酶自磷酸化状态和催化活性的变化,结果发现质膜上一个57kD的蛋白激酶分子上有多个自磷酸化位点,而且自磷酸化反应能提高该酶催化组蛋白H1磷酸化的激酶活力。进一步的研究表明诱导衰老处理造成的57kD蛋白激酶自磷酸化状态的变化,可能对调节它在衰老过程中催化活性的变化起重要作用;而外源6－BA预处理则能够维持57kD蛋白激酶体内高自磷酸化状态,保持该激酶在衰老过程中的催化活力。对衰老和6－BA过程中质膜上39和47kD蛋白激酶自磷酸化状态变化的研究表明,这两种激酶可能参与大豆叶片对6－BA刺激信号的传导和／或应答反应过程。     

植物种子衰老与线粒体关系的研究进展

种子的衰老是一个复杂的从量变到质变的生物学过程。种子衰老与线粒体功能异常密切相关,衰老的线粒体学说认为,线粒体中活性氧的过量产生是种子衰老的主要原因。深入了解种子衰老过程中线粒体的变化对于揭示种子衰老机理和种子安全保存具有重要意义。本文主要介绍了当前有关种子衰老过程中线粒体结构、呼吸作用和抗氧化系统的研究现状,并对种子衰老与线粒体关系研究中存在的问题进行了讨论。     

酿酒酵母细胞衰老机理的研究进展

酿酒酵母的细胞衰老研究作为生命科学领域的前沿课题,对解析高等真核生物衰老的分子机制具有重要意义。迄今为止,在酵母中已经确立的衰老模式有两种,即复制型衰老和时序型衰老。细胞衰老的影响因子较多,涉及到很多过程,所以研究起来非常复杂。综述了两种细胞衰老机制的研究进展。     

DNA 与衰老

衰老是生物体各种功能的普遍衰弱,以及抵抗环境伤害和恢复生理稳态的降低过程。衰老、衰老的原因、衰老的机理及衰老与疾病、衰老与死亡的关系,一直是生物及医学领域的科学家们积极探讨的问题。衰老这一极其复杂的生物学过程,涉及物理、化学、生物、医学诸领域。现已发展的近300种衰老学说分别从整体、器官、细胞、分子水平对生物衰老的机制进行了阐述。本文将从分子的角度阐述生物信息分子－DNA及其相关物质与生物衰老的关系。     

DNA甲基化与衰老研究进展

DNA甲基化与衰老的研究是近年来生命科学领域研究的热点之一。综述了DNA甲基化理论研究进展和探讨影响甲基化与衰老的主要因素,以揭示两者之间可能存在的联系。     

端粒和端粒酶与衰老研究

衰老是一种多因素的复合调控过程,表现为染色体端粒长度的改变、DNA损伤、DNA的甲基化和细胞的氧化损伤等,并已形成了许多学说,而端粒学说成为衰老研究的热点之一.对与衰老紧密相关的因素———端粒、端粒酶的结构及其与衰老关系的研究进展进行综述,阐明对端粒—端粒酶的作用将会在抗衰老方面有着十分重要的理论价值及实际意义.     

浅谈生命科学的发展对人类生活的影响

回顾了生命科学的主要发展历程,对20世纪中叶以来生命科学的发展趋势作了简要介绍。20世纪70年代诞生的基因工程及PCR技术、克隆技术和干细胞研究等现代生物技术,使生命科学的发展进入了一个新阶段,这些以创造或改变生物类型及生物机能为目标的现代生物技术已成为新技术革命的三大支柱之一。通过探寻生命本质及生长发育、疾病、衰老等奥秘,揭示生命现象的内在规律。随着生物技术在医药、食品化工、农业、环保以及能源、采矿等工业部门中的广泛应用,它正在对人类经济及社会生活和社会进步产生深刻而广泛的影响。     

Mitochondria and aging: A role for the mitochondrial transition pore?

The cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.     

Robustness and aging—A systems-level perspective

The theory of robustness describes a system level property of evolutionary systems, which predicts tradeoffs of great interest for the systems biology of aging, such as accumulation of non-heritable damage, occurrence of fragilities and limitations in performance, optimized allocation of restricted resources and confined redundancies. According to the robustness paradigm cells and organisms evolved into a state of highly optimized tolerance (HOT), which provides robustness to common perturbations, but causes tradeoffs generally characterized as “robust yet fragile”. This raises the question whether the ultimate cause of aging is more than a lack of adaptation, but an inherent fragility of complex evolutionary systems. Since robustness connects to evolutionary designs, consideration of this theory provides a deeper connection between evolutionary aspects of aging, mathematical models and experimental data. In this review several mechanisms influential for aging are re-evaluated in support of robustness tradeoffs. This includes asymmetric cell division improving performance and specialization with limited capacities to prevent and repair age-related damage, as well as feedback control mechanisms optimized to respond to acute stressors, but unable to halt nor revert aging. Improvement in robustness by increasing efficiencies through cellular redundancies in larger organisms alleviates some of the damaging effects of cellular specialization, which can be expressed in allometric relationships. The introduction of the robustness paradigm offers unique insights for aging research and provides novel opportunities for systems biology endeavors.     

Trends in oxidative aging theories

The early observations on the rate-of-living theory by Max Rubner and the report by Gershman that oxygen free radicals exist in vivo culminated in the seminal proposal in the 1950s by Denham Harman that reactive oxygen species are a cause of aging (free radical theory of aging). The goal of this review is to analyze recent findings relevant in evaluating Harman's theory using experimental results as grouped by model organisms (i.e., invertebrate models and mice). In this regard, we have focused primarily on recent work involving genetic manipulations. Because the free radical theory of aging is not the only theorem proposed to explain the mechanism(s) involved in aging at the molecular level, we also discuss how this theory is related to other areas of research in biogerontology, specifically, telomere/cell senescence, genomic instability, and the mitochondrial hypothesis of aging. We also discuss where we think the free radical theory is headed. It is now possible to give at least a partial answer to the question whether oxidative stress determines life span as Harman posed so long ago. Based on studies to date, we argue that a tentative case for oxidative stress as a life-span determinant can be made in Drosophila melanogaster. Studies in mice argue for a role of oxidative stress in age-related disease, especially cancer; however, with regard to aging per se, the data either do not support or remain inconclusive on whether oxidative stress determines life span.     

Is the oxidative stress theory of aging dead?

Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.     

The soma-germline communication: implications for somatic and reproductive aging

Aging is characterized by a functional decline in most physiological processes, including alterations in cellular metabolism and defense mechanisms. Increasing evidence suggests that caloric restriction extends longevity and retards age-related diseases at least in part by reducing metabolic rate and oxidative stress in a variety of species, including yeast, worms, flies, and mice. Moreover, recent studies in invertebrates – worms and flies, highlight the intricate interrelation between reproductive longevity and somatic aging (known as disposable soma theory of aging), which appears to be conserved in vertebrates. This review is specifically focused on how the reproductive system modulates somatic aging and vice versa in genetic model systems. Since many signaling pathways governing the aging process are evolutionarily conserved, similar mechanisms may be involved in controlling soma and reproductive aging in vertebrates.     

New model systems for studying the evolutionary biology of aging: Crustacea

Progress in any area of biology has generally required work on a variety of organisms. This is true because particular species often have characteristics that make them especially useful for addressing specific questions. Recent progress in studying the evolutionary biology of senescence has been made through the use of new species, such asCaenorhabditis elegans andDrosophila melanogaster, because of the ease of working with them in the laboratory and because investigators have used theories for the evolution of aging as a basis for discovering the underlying mechanisms.I describe ways of finding new model systems for studying the evolutionary mechanisms of aging by combining the predictions of theory with existing information about the natural history of organisms that are well-suited to laboratory studies. Properties that make organisms favorable for laboratory studies include having a short generation time, high fecundity, small body size, and being easily cultured in a laboratory environment. It is also desirable to begin with natural populations that differ in their rate of aging. I present three scenarios and four groups of organisms which fulfill these requirements. The first two scenarios apply to well-documented differences in age/size specific predation among populations of guppies and microcrustacea. The third is differences among populations of fairy shrimp (anostraca) in habitat permanence. In all cases, there is an environmentla factor that is likely to select for changes in the life history, including aging, plus a target organism which is well-suited for laboratory studies of aging.     

Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin

The discovery of melatonin and its derivatives as antioxidants has stimulated a very large number of studies which have, virtually uniformly, documented the ability of these molecules to detoxify harmful reactants and reduce molecular damage. These observations have clear clinical implications given that numerous age-related diseases in humans have an important free radical component. Moreover, a major theory to explain the processes of aging invokes radicals and their derivatives as causative agents. These conditions, coupled with the loss of melatonin as organisms age, suggest that some diseases and some aspects of aging may be aggravated by the diminished melatonin levels in advanced age. Another corollary of this is that the administration of melatonin, which has an uncommonly low toxicity profile, could theoretically defer the progression of some diseases and possibly forestall signs of aging. Certainly, research in the next decade will help to define the role of melatonin in age-related diseases and in determining successful aging. While increasing life span will not necessarily be a goal of these investigative efforts, improving health and the quality of life in the aged should be an aim of this research.