线粒体代谢介导的表观遗传改变与衰老研究

线粒体是细胞物质代谢与能量代谢的中心,在多种生理和病理过程中扮演着重要角色。表观遗传修饰是一种独立于DNA序列并在建立与维持特定基因表达谱中发挥主要作用的遗传调控模式。近年来的研究表明,线粒体能量代谢通过中间产物,介导线粒体–核信号的传递,调节染色质的表观修饰状态,进而影响基因表达。线粒体代谢紊乱可以诱导表观遗传重编程,进而启动衰老表型及退行性疾病的发生。本文综述了线粒体代谢与染色质表观遗传修饰关系的研究进展,探讨了线粒体应激在染色质重组中发挥的作用,展望了其在认知功能障碍等衰老相关性疾病研究中的前景。     

综述: 细胞自噬和线粒体质量控制与健康衰老

拥有健康的晚年是每一个人的祈盼,这也是目前应对即将到来的社会老龄化危机而需要解决的重要课题.实现健康衰老需要对人类衰老发生的机制有深入的了解,比如在此过程中扮演着重要角色的线粒体的研究.线粒体是细胞能量和自由基代谢中心,也是细胞凋亡调控中心,并在信号转导和基因表达调控中发挥重要作用.线粒体一旦受损,一方面能量代谢发生紊乱,另一方面产生大量自由基,影响细胞的正常生长,并导致细胞甚至机体的衰老.正常情况下,细胞通过自噬溶酶体机制选择性清除受损伤和不需要的线粒体,这是线粒体质量控制的重要机制.研究发现,线粒体质量控制异常可能在衰老发生过程中起关键作用.限食及增强运动能有效促进线粒体质量控制,改善线粒体功能并延缓衰老.     

细胞自噬和线粒体质量控制与健康衰老

拥有健康的晚年是每一个人的祈盼,这也是目前应对即将到来的社会老龄化危机而需要解决的重要课题.实现健康衰老需要对人类衰老发生的机制有深入的了解,比如在此过程中扮演着重要角色的线粒体的研究.线粒体是细胞能量和自由基代谢中心,也是细胞凋亡调控中心,并在信号转导和基因表达调控中发挥重要作用.线粒体一旦受损,一方面能量代谢发生紊乱,另一方面产生大量自由基,影响细胞的正常生长,并导致细胞甚至机体的衰老.正常情况下,细胞通过自噬溶酶体机制选择性清除受损伤和不需要的线粒体,这是线粒体质量控制的重要机制.研究发现,线粒体质量控制异常可能在衰老发生过程中起关键作用.限食及增强运动能有效促进线粒体质量控制,改善线粒体功能并延缓衰老.     

导言

线粒体是细胞内具有双层膜结构和独立基因组DNA的重要细胞器,在细胞生命活动中发挥着至关重要的作用。一方面它们是真核细胞的主要能量工厂,通过有氧代谢产生ATP,为细胞生命活动提供能量;另一方面,线粒体是细胞内活性氧产生中心,同时也是细胞内主要钙库之一,调节细胞内钙信号和细胞生长活动。更为重要的是,线粒体还是细胞凋亡和衰老的调控中心。在细胞凋亡过程中,线粒体释放促凋亡因子（如细胞色素C）,对细胞内凋亡信号进行整合和放大。不言而喻,线粒体在细胞生长、衰老和凋亡等生理、病理过程中扮演着重要的角色。     

线粒体自噬与心肌衰老

线粒体(mitochondrion)是一种存在于大多数真核细胞中由双层膜包被的细胞器,是细胞进行有氧呼吸和能量来源的主要场所。由于各种因素导致的线粒体损伤及功能紊乱,是细胞潜在的危险因素,必需及时清除,以维持细胞内环境稳态。而细胞内受损的线粒体主要通过选择性的自噬过程,即线粒体自噬来介导清除。对于心肌细胞这种有丝分裂后细胞,线粒体自噬功能的改变对其细胞质量控制的影响尤为显著。在生理状态及应激状态下,多种因子可调控心肌细胞线粒体自噬,进而发挥心肌细胞质量控制的作用。近年来多项研究均表明,线粒体自噬与心肌衰老之间存在着密切的联系。本文现就线粒体自噬及其与心肌衰老的关系进行综述。     

运动与衰老:线粒体功能和氧化还原的调控

衰老与线粒体功能衰退和氧化还原失衡紧密相关。随着年龄的增加,肌肉线粒体的DNA丰度和蛋白质的合成不断的下降,线粒体代谢过程中的副产物自由基增加导致脂质,蛋白质和核酸等大分子的氧化损伤不断累积。衰老相关的线粒体功能的下降和氧化还原失衡影响运动功能,导致胰岛素抵抗和神经退行性疾病,因而对于调节寿命起到重要的作用。因而线粒体可能是决定寿命的重要因素。大量研究证实长期运动训练可以很大程度预防和改善衰老相关疾病,其机制可能是通过促进线粒体生成和激活内源性抗氧化防御体系而提高线粒体功能和调控氧化还原平衡。因此,长期的运动训练预防衰老相关疾病和提高老年人的生命质量很可能是通过调控线粒体功能和氧化还原平衡而发挥作用。     

线粒体靶向的活性氧荧光探针的研究进展

线粒体作为细胞的能量工厂,是细胞中活性氧(reactive oxygen species,ROS)的主要来源。活性氧在诸多生理和病理过程中发挥着重要作用,有证据表明其与衰老、癌症、神经退行性疾病等相关,因此越来越受到人们的关注。一直以来,由于活性氧种类较多,活性较高,特异性地准确检测线粒体内的活性氧存在诸多问题和挑战,其中一种策略是运用线粒体靶向荧光探针。本文介绍了近年来靶向线粒体的选择性活性氧荧光探针的策略和设计方法,介绍其应用并展望未来研究趋势。     

线粒体DNA突变与衰老关系的研究进展

衰老的分子机制复杂,目前的研究尚未能对衰老的关键轴心获得一致而明晰的理论认识,各种衰老假说相继被提出,其中具有代表性的为端粒学说。端粒-p53-线粒体衰老轴线自从被提出,已经获得越来越多的实验论证,较多的研究也表明线粒体DNA突变与衰老有着密切的相关性,但突变与衰老之间的因果关系存在较大争议。我们简要综述了近年来线粒体DNA突变与衰老关系的相关研究进展。     

运动调节内质网应激和线粒体自噬防治衰老相关疾病研究进展

随着我国逐渐步入老龄化社会,衰老及其相关疾病的预防和治疗措施已成为研究的热点问题。机体老化引起老年人常见的慢性疾病如阿尔茨海默病、心血管疾病、肌肉减少症和骨质疏松等是影响老年人身体健康和造成死亡的重要威胁。内质网和线粒体是机体蛋白质合成和能量供应的主要细胞器,对于细胞内稳态调节起主导作用,在机体老化过程中细胞内的动态平衡被打破,从而加剧各器官老化,并且伴随着衰老相关疾病发生。而运动作为一种有效的非药物干预手段,对于延缓衰老预防衰老相关疾病的发生起到保护作用。本文从内质网应激、线粒体自噬两个方面入手,综述了衰老相关疾病阿尔兹海默病、心血管疾病、肌肉减少症以及骨质疏松等的相关分子机制,并且阐述运动干预之后各疾病相关分子机制变化,进一步论述了衰老机体中运动调节内质网应激和线粒体自噬及运动干预后发挥保护效应的分子机制,拟为运动延缓机体衰老及预防老年性相关疾病的发生提供新的思路和理论依据。     

运动调控衰老骨骼肌UPRmt和线粒体自噬互作的机制

衰老性肌萎缩中的线粒体功能障碍与线粒体未折叠蛋白反应(mitochondrial unfolded protein response,UPRmt)和线粒体自噬构成的线粒体质量控制(mitochondrial quality control, MQC)的损伤密切相关。线粒体质量控制是线粒体维持内环境稳态的保护机制，其中UPRmt和线粒体自噬分别负责受损线粒体的修复和清除。UPRmt应对未折叠蛋白应激，维持线粒体和细胞蛋白质稳态，延长寿命并调节代谢重构，而线粒体自噬选择性地去除受损严重的线粒体，两者共同维护线粒体稳态。本文总结UPRmt与线粒体自噬的互作、衰老骨骼肌UPRmt与线粒体自噬的变化和运动逆转衰老骨骼肌UPRmt和线粒体自噬的机制，重点总结运动源的活性氧(reactive oxygen species, ROS)调控UPRmt与线粒体自噬互作的信号通路研究进展，并为衰老性肌萎缩进程中线粒体质量控制的维持提供参考。     

植物种子老化的生理学研究进展

种子品质的优劣对于农牧业生产、经济与遗传资源有效利用、生物多样性保护以及植物群落恢复与重建具有重要的作用.种子老化是其在贮藏过程中普遍存在的一种生理现象,是随着种子贮藏时间延长而发生和发展的自然不可逆过程,不仅关系到后续种、苗生长与产量、品质等问题,还对植物种质资源的保存、利用和开发等均具有重要影响.种子老化的生理机制...     

Function and stress tolerance of seed mitochondria

Seeds of higher plant are desiccation tolerant, which suggests that their mitochondria exhibit particular properties. Insight into the function of seed mitochondria, especially in legume and model plants, has been fostered by the development of proteomics. Seed mitochondria are functional at the onset of imbibition, and their integrity and performance systematically improves during germination. This suggests that repair and biogenesis mechanisms exist, and this is supported by morphological and biochemical evidence. Seed mitochondria generate and operate in a hypoxic environment. They accumulate stress proteins, such as a small heat-shock protein and a late embryogenesis abundant protein. The mitochondria of pea ( Pisum sativum L.) seed also display a biased phospholipid composition likely to favour desiccation tolerance. These specific biochemical properties surely contribute to the remarkable tolerance of seed mitochondria to extreme temperatures. Recent progress towards the resolution of the seed mitochondrial proteome is discussed in light of the growing body of genomic data.     

Os4BGlu14, a monolignol β-Glucosidase,negatively affects seed longevity by influencing primary metabolism in rice

Plant Molecular Biology - Os4BGlu14, a monolignol β-glucosidase, plays a negative role in seed longevity by affecting primary metabolism during seed development and aging. Seed longevity is a...     

种子老化的生理生化与分子机理研究进展

种子作为植物遗传资源的有效保存体以及重要的种质创新原料,其老化或者劣变将直接导致发芽率、活力、生活力降低,抑制种胚正常发育以及幼苗生长,由此造成植物生产水平及其品质大幅下降。这也将进一步涉及因种质资源匮乏、土壤种子库系统功能紊乱所引发的全球生物多样性减小、草地退化和荒漠化加剧等生态危机问题。对种子老化生理生化特性和分子机理等研究进行了综述。总结了近年来关于种子老化涉及的理化反应包括保护酶活性的改变、核酸以及蛋白质的分解、内源激素的消长、质膜完整性降低等相关研究;并从蛋白代谢、核酸代谢、种子含水量以及基因重组等多角度总结和阐述了与老化机理有关的最新研究观点,以期为种子老化、种子活力修复和种子寿命延长等机理研究提供基础理论参考。目前对种子老化的研究多集中于传统的生理生化过程和内外影响因子相对独立变化的片段性研究,缺乏系统综合的多层面体系研究。种子作为生命体,随着探讨生命衰老机理的生物技术日新月异,通过蛋白组学、酶学、基因工程技术、转录组测序等新技术的应用,必将对未来种子老化机理机制的揭示有突破性推进作用。     

Comparative Transcriptomic Analysis of Two Rice (Oryza sativa L.) Male Sterile Line Seed Embryos Under Accelerated Aging

Plant Molecular Biology Reporter - Seed aging is a complex and irreversible process during seed development and storage. The quality of parental seeds affects yield and quality of hybrid rice seeds...     

Genetic analysis of seed-soluble oligosaccharides in relation to seed storability of Arabidopsis

Seed oligosaccharides (OSs) and especially raffinose series OSs (RSOs) are hypothesized to play an important role in the acquisition of desiccation tolerance and consequently in seed storability. In the present work we analyzed the seed-soluble OS (sucrose, raffinose, and stachyose) content of several Arabidopsis accessions and thus identified the genotype Cape Verde Islands having a very low RSO content. By performing quantitative trait loci (QTL) mapping in a recombinant inbred line population, we found one major QTL responsible for the practically monogenic segregation of seed stachyose content. This locus also affected the content of the two other OSs, sucrose, and raffinose. Two candidate genes encoding respectively for galactinol synthase and raffinose synthase were located within the genomic region around this major QTL. In addition, three smaller-effect QTL were identified, each one specifically affecting the content of an individual OS. Seed storability was analyzed in the same recombinant inbred line population by measuring viability (germination) under two different seed aging assays: after natural aging during 4 years of dry storage at room temperature and after artificial aging induced by a controlled deterioration test. Thus, four QTL responsible for the variation of this trait were mapped. Comparison of the QTL genetic positions showed that the genomic region containing the major OS locus did not significantly affect the seed storability. We concluded that in the studied material neither RSOs nor sucrose content had a specific effect on seed storability.     

Lipid peroxidation and peroxide-scavenging enzymes associated with accelerated aging of peanut seed

Accelerated aging is known to reduce seed viability and vigor in many crop species. The phenomenon is due in part to aging-induced lipid peroxidation, which has the potential to damage membranes of the seed tissues. This study was undertaken to evaluate the effect of accelerated aging on germinability and several physiological characteristics related to peroxidation in the seed of two peanut cultivars. Accelerated aging was achieved by incubating seed at 45°C and 79% relative humidity in a closed chamber for 3, 6, or 9 days. The results indicate that accelerated aging inhibited seed germination and seedling growth. Enhanced lipid peroxidation and increased peroxide accumulation were observed in the axis and cotyledons of aged seed. Accelerated aging also inhibited the activity of superoxide dismutase, peroxidase, ascorbate peroxidase, and lipoxygenase. Seed axes appeared to be more susceptible to aging than cotyledons. The changes in germination and physiological activities, expressed as a function of aging duration, were similar in the two cultivars, despite differences in their seed weight.     

Enhancing seed quality and viability by suppressing phospholipase D in Arabidopsis

Seed aging decreases the quality of seed and grain and results in agricultural and economic losses. Alterations that impair cellular structures and metabolism are implicated in seed deterioration, but the molecular and biochemical bases for seed aging are not well understood. Ablation of the gene for a membrane lipid-hydrolyzing phospholipase D (PLDalpha1) in Arabidopsis enhanced seed germination and oil stability after storage or exposure of seeds to adverse conditions. The PLDalpha1-deficient seeds exhibited a smaller loss of unsaturated fatty acids and lower accumulation of lipid peroxides than did wild-type seeds. However, PLDalpha1-knockdown seeds were more tolerant of aging than were PLDalpha1-knockout seeds. The results demonstrate the PLDalpha1 plays an important role in seed deterioration and aging in Arabidopsis. A high level of PLDalpha1 is detrimental to seed quality, and attenuation of PLDalpha1 expression has the potential to improve oil stability, seed quality and seed longevity.     

Seed Dynamics in Relation to Gaps in a Tropical Montane Rainforest of Hainan Island, South China： （I） Seed Rain

Seed dynamics is an important part of stand dynamics in forest ecosystems. In this paper, 26 gaps were randomly selected to study the influence of gaps on the spatial and temporal patterns of seed rains in a tropical montane rainforest of Hainan Island, South China. Three zones for each gap, including outside gap zone （Non-gap）, transitional gap zone （EG-CG）, and central gap zone （CG）, were designed, and fourseed traps （each lm x lm in size） were placed in each zone. Seed rains were collected by these traps every 10 days from June 2001 to May 2002. Seed rain varied greatly with season and generally exhibited a pattern of unimodal change during the study period： seed abundance and species richness were both greater in the wet season than in the dry season. Gaps significantly influenced the temporal patterns of both species richness and density of seed rains. Gaps had no significant influences on the spatial distribution patterns of seed rain species richness, but significantly affected the spatial distribution pattern of seed rain densities. Among the three different zones of gaps, the outside gap zone generally received more seeds inputs than the two other gap zones.     

麻疯树种子发育过程中脂类物质变化的显微和超微结构观察

用石蜡切片、半薄切片和超薄切片方法研究了麻疯树种子发育过程中脂类物质的变化。结果表明:脂类物质主要储存于胚乳当中,当种子发育成熟时胚乳中迅速积累了大量的油脂;种皮在发育过程中脂类物质含量较多,成熟时外种皮硬化,内种皮含有大量的油脂;种子成熟时胚中含有少量的脂类物质。细胞内脂类物质含量比较多时,内质网、线粒体、质体和高尔基体数量也会较多。种子完全成熟时进行采收加工是最为合适的。