（11.29 -- 12.05 / 2010）
恒峰g22国际集团:陶国新 

　　本周动态蕴含以下内容：老鼠尝试批注建复端Ｄ芄荒孀ダ；发现新的抗癌免疫细胞；Lkb1推进造血干细胞生计；成熟血细胞与其亲代干细胞的信息反
；分子“开关”影响衰老和代谢疾
；共生菌影响果蝇的交配偏差
。

1. 老鼠尝试批注建复端Ｄ芄荒孀ダ
【提要】
　　据香港《文汇报》11月30日报路，哈佛科学家最近破天荒地令大哥的老鼠器官获得新生，成功逆转衰老过程，这项突破成就或有望防治脑退化症(老人痴呆症)、糖尿病和心脏病等疾病，甚至有望打开永恒青春的奥秘，进一步迈向研造“永生不老药”
？蒲г又尽短烊弧吠28日登载美国哈佛医学院的科研汇报，钻研员豢养了一些经基因刷新的老鼠，令它们因不足“端粒酶”(telomerase)而未老先衰，出现嗅觉衰退、脑部缩幼、不育、肠部和脾脏受损等疾病，使它们皮肤、大脑、内脏和其它器官老化
。
所谓“端粒”，是指染色体结尾的DNA反复序列，作用是维持染色体的齐全性
。“端粒”的长度反映着细胞复造史及复造潜能，被称作细胞寿命的“有丝割裂钟”
。报路称，科研人员将这些老鼠分为两组，把一种名为“4-羟基他莫昔芬”的按时开释药物，植入其中一组老鼠的皮下，重启它们体内休眠的“端粒酶”基因
。了局在短短1个月内，注射药物的老鼠体内长出很多新的细胞，重要器官运作职能改善，身段差不多齐全“仿废还童”，雄性老鼠更复原生育职能
。注射药物的尝试鼠最终活到正常鼠的寿命，但并不比通常鼠寿命长
。
进行钻研的德皮尼奥博士暗示，尝试鼠对人类而言，就像一个40岁的人，身段未老先衰像80多岁的老人，而这项尝试逆转衰老过程，把他变回50岁通常
。德皮尼奥说：“这些是严重衰老的动物，但经过一个月医治后，它们已有具体康复迹象，蕴含脑部长出新的细胞
。”他指出，这是初次有老鼠尝试成功把衰老过程逆转，意味着一些老化的器官也佑装更生”的可能
。
不外，要把这一科技利用于人体身大将会较作难题，老鼠毕生中都能造作端粒酶，但是人类到成年后便会自动“关掉」剽种基因，从而阻止细胞增长失控，以免转化成癌症
。因而，提升人体的“端粒酶”水平固然或有助减缓衰老速度，但同时增长患癌的风险
。德皮尼奥以为，“TERT”疗法若是是分阶段进行，和只用于身段没有癌细胞及较为年轻的人身上，疗法或对人体安全
。牛津大学生物化学家考克斯以为，这项钻延装极度重要”，证明准则上短期复原成人体内的“端粒”，能令大哥的组织更生和复原生理职能
。（起源：中国新闻网 颁布功夫：2010-11-30 11:05:34）

【点评】
　　该基因刷新老鼠试验第一次在动物身上实现了通过建复端粒而“仿废还童”，固然在正常衰老的老鼠身上还未有钻研以及利用在人体上还遥遥无期，但是它证了然复原端Ｄ芄荒孀ダ
。这在动物尝试方面为人体再生复原科学再添有利证据，证明衰老组织是能够复原到年轻态的
。

【原文摘录】Nature advance online publication doi:10.1038/nature09603
Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
Mariela Jaskelioff, Florian L. Muller, Ji-Hye Paik, et al.
An ageing world population has fuelled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase-deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signalling activation in vivo1. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure and impaired tissue injury responses. Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-oestrogen receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice have short dysfunctional telomeres and sustain increased DNA damage signalling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signalling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2+ neural progenitors, Dcx+ newborn neurons, and Olig2+ oligodendrocyte populations. Consistent with the integral role of subventricular zone neural progenitors in generation and maintenance of olfactory bulb interneurons, this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.

2. 发现新的抗癌免疫细胞

【提要】
　　丹麦科研人员不久前发现一种新的免疫细胞能协助抵抗癌症
。他们正据此研造一种新型癌症疫苗，目前在进行临床试验
。人体免疫抑造细胞和癌细胞能够产生一种特殊的双加氧酶，来抑造免疫细胞的攻击性，使其不足足够攻击力抵抗癌细胞侵袭，甚至还会被癌细胞吞噬
。双加氧酶的存在使现有癌症疫苗的有效性大打折扣
。丹麦海莱乌医院癌症免疫医治中心的钻研者在最新一期美国粹术刊物《血液》上汇报说，他们发现人体免疫系统中存在一种此前未知的细胞，这种细胞能够杀死那些产生双加氧酶的细胞
。新发现的细胞在扑灭免疫抑造细胞的同时，还能直接攻击癌细胞
。
辅导这项钻研的马斯·哈尔·安德森说，钻研幼组在研造一种新型癌症疫苗，通过增长上述抗癌细胞的数量，提高机体免疫系统的攻击力，从而抵抗癌症
。海莱乌医院正用新疫苗对一些肺癌患者发展临床试验，目前的医治成效显著好于通例疗法
。钻研幼组以为，从道理上说，这种可有效抑造双加氧酶产生的癌症疫苗有望与其他疗法协同医治多种癌症
。（起源：新华网 2010-12-2 10:33:22）

【点评】
新的免疫细胞既能扑灭免疫抑造细胞，还能直接攻击癌细胞，对于匹敌癌细胞是好新闻
。但是另一方面，新的免疫细胞的数量和活力必要幼心节造，是否会导致自体免疫问题也必要进一步澄清
。

【原文摘录】Blood, Nov 2010; doi:10.1182/blood-2010-06-288498
Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators
Rikke Bæk Sørensen, Sine Reker Hadrup, Inge Marie Svane, et al.
Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathological settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in cancer patients but also in healthy individuals. We show that the presence of such IDO-specific CD8+ T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO+ suppressive cells. This had profound effects on the balance between IL-17-producing CD4+ T cells and regulatory T cells. Furthermore, this caused an increase in the production of the pro-inflammatory cytokines IL-6 and TNF- while decreasing the IL-10 production. Finally, the addition of IDO-inducing agents (i.e. the TLR9 ligand CpG, soluble CTLA4 or IFN-) induced IDO-specific T cells among PBMC from cancer patients as well as healthy donors. In the clinical setting, IDO may serve as an important and widely applicable target for immunotherapeutic strategies where IDO play a significant regulatory role. The present describe for the first time effector T cells with a general regulatory function that may play a vital role for the mounting or maintaining of an effective adaptive immune response. We suggest terming such effector T cells "supporter T cells".

3. Lkb1推进造血干细胞生计

【提要】
　　造血干细胞对高能和氧化压力极度敏感，对它们的静止与增殖之间的平衡进行调控是响应代谢压力、同时维吃熹持久再生能力所必要的
。新的钻研批注，Lkb1肿瘤抑造因子和代谢传感器在维持造血细胞的能量平衡中起关键作用，被发现是细胞周期调控及能量平衡所必须的，造血干细胞细胞周期调节和生计对Lkb1的依赖性要强于其他造血细胞
。

【点评】
　　对造血干细胞的性命属性和代谢机造又多了些相识
。

【原文摘录】Nature doi:10.1038/nature09571
Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells
Daisuke Nakada, Thomas L. Saunders & Sean J. Morrison
Little is known about metabolic regulation in stem cells and how this modulates tissue regeneration or tumour suppression. We studied the Lkb1 tumour suppressor and its substrate AMP-activated protein kinase (AMPK), kinases that coordinate metabolism with cell growth. Deletion of the Lkb1 (also called Stk11) gene in mice caused increased haematopoietic stem cell (HSC) division, rapid HSC depletion and pancytopenia. HSCs depended more acutely on Lkb1 for cell-cycle regulation and survival than many other haematopoietic cells. HSC depletion did not depend on mTOR activation or oxidative stress. Lkb1-deficient HSCs, but not myeloid progenitors, had reduced mitochondrial membrane potential and ATP levels. HSCs deficient for two catalytic α-subunits of AMPK (AMPK-deficient HSCs) showed similar changes in mitochondrial function but remained able to reconstitute irradiated mice. Lkb1-deficient HSCs, but not AMPK-deficient HSCs, exhibited defects in centrosomes and mitotic spindles in culture, and became aneuploid. Lkb1 is therefore required for HSC maintenance through AMPK-dependent and AMPK-independent mechanisms, revealing differences in metabolic and cell-cycle regulation between HSCs and some other haematopoietic progenitors.

4. 成熟血细胞与其亲代干细胞的信息反馈

【提要】
　　澳大利亚墨尔本Walter and Eliza Hall Institute的一项最新钻研批注成熟血细胞可能与亲代干细胞“沟通”，并影响其行为
；迥谘赴蠢』返姆⑾治暄懈上赴艽砺乙鸬募膊〖翱⑿碌囊街尾街杵舴⒘诵侣仿
。钻研了局颁发在11月29日的PNAS上，揭示了早年未知的血细胞间的互有关系
。
来自分子医学系的Carolyn de Graaf博士和Doug Hilton教授以及来自癌症和血液病学系的Warren Alexander辅导了该项钻研
。“我们知路血液干细胞可天生所有类型的成熟血细胞
？蒲Ъ颐且幌虿虏馐潜聿康某煞值骺亓搜赴焐，并且两个群体相互孤立存在，”Hilton教授说：“然而新钻研批注成熟细胞事实上可反作用于干细胞，扭转其基因表白以及影响它们的行为
。”钻研人员发现血细胞异？梢鸱蠢』肥У，进而对血液干细胞产生影响
。钻研人员在动物模型中钻研了一种抑造血幼板天生的转录因子Myb，在检测Myb缺失对细胞的影响时发现了这一景象
。de Graaf博士说Myb基因缺失可导致动物血液中产生高水平的血幼板，从而引起维持干细胞的信号蹊径发生扭转
。“当信号蹊径发生扭转时，这些干细胞不再维持在一种‘静止状态’，而是在不休地循环，天生成熟干细胞，”de Graaf博士说：“最终干细胞会耗尽，由于不足足够的干细胞天生新的红细胞和白细胞，从而导致机体血液疾病发生
。”此表，钻研人员还利用新一代的基因组技术鉴定了缺点信号所致的血液干细胞中的基因象征
。这些基因象征有可能在将来用于诊断和辅助疾病医治
。“若是我们可能相识这些基因在干细胞维持和血细胞天生中的重要作用，我们就可能找到一些新蹊径提高移植技术和血液疾病的医治，”de Graaf博士说
。Hilton教授以为新发现将使那些干细胞衰竭的患者受益
。“我们所要做的事件就是确定这些干细胞的衰竭是否是由于成熟血细胞和干细胞之间的谬误沟通所致，这些发现将有可能促使我们找到新的蹊径医治这些疾病，”Hilton教授说
。（Science Daily 2010-12-1 10:23:13 ）

【点评】
　　干细胞的活动法规受到机体的系统调控，成熟细胞会反馈信息到调控体下反调节干细胞的活动
。注明一个别下凤的高低游部门不是相互独立的，一个整体里的各个别是互有关联的，一个个别的异常影响的不仅仅是自身
。   
【原文摘录】PNAS  doi: 10.1073/pnas.1016166108
Regulation of hematopoietic stem cells by their mature progeny
Carolyn A. de Graafa,b, Maria Kauppic, et al.
Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence. Mpl also controls circulating TPO concentration via receptor-mediated internalization and degradation. Here, we demonstrate that the megakaryocytosis and increased platelet mass in mice with mutations in the Myb or p300 genes causes reduced circulating TPO concentration and TPO starvation of the stem-cell compartment, which is exacerbated because these cells additionally exhibit impaired responsiveness to TPO. HSCs from MybPlt4/Plt4 mice show altered expression of TPO-responsive genes and, like HSCs from Tpo and Mpl mutant mice, exhibit increased cycling and a decline in the number of HSCs with age. These studies suggest that disorders of platelet number can have profound effects on the HSC compartment via effects on the feedback regulation of circulating TPO concentration.

5. 分子“开关”影响衰老和代谢疾病

【提要】
　　来自Harvard School of Public Health的科学家发现一种分子“开关”可能关关某些细胞过程来抵抗衰老和代谢疾病
。只管还必要更多的钻研，这一发现很可能有助于开发新的蹊径来终止或减慢诸如2型糖尿病和心脏病等代谢疾病的进展
。用基因刷新的老鼠模型，钻研衰老过程中转录辅抑造物SMRT (silencing mediator of retinoid and thyroid hormone receptors)蛋白的作用，发现衰老细胞堆集了更多的SMRT蛋白
。在大无数代谢组织中SMRT的表白和结合到PPAR受体随春秋增长
。SMRT通过RID1和RID2两个结构域调节核受体信号蹊径
。通过基因工程选择性失活RID1，使SMRT结合转移到RID2有关核受体，加强了细胞对氧化危险的敏感性，引起早衰和有关代谢疾病伴有线粒体职能降低和抗氧化基因表白
。

【点评】
　　该钻研丰硕了对于衰老的理解和抗老化蹊径的索求
。

【原文摘录】Cell Metabolism, 2010; DOI: 10.1016/j.cmet.2010.11.007
Nuclear Receptor Corepressor SMRT Regulates Mitochondrial Oxidative Metabolism and Mediates Aging-Related Metabolic Deterioration.
Shannon M. Reilly, Prerna Bhargava, Sihao Liu, et al.
The transcriptional corepressor SMRT utilizes two major receptor-interacting domains (RID1 and RID2) to mediate nuclear receptor (NR) signaling through epigenetic modification. The physiological significance of such interaction remains unclear. We find SMRT expression and its occupancy on peroxisome proliferator-activated receptor (PPAR) target gene promoters are increased with age in major metabolic tissues. Genetic manipulations to selectively disable RID1 (SMRTmRID1) demonstrate that shifting SMRT repression to RID2-associated NRs, notably PPARs, causes premature aging and related metabolic diseases accompanied by reduced mitochondrial function and antioxidant gene expression. SMRTmRID1 cells exhibit increased susceptibility to oxidative damage, which could be rescued by PPAR activation or antioxidant treatment. In concert, several human Smrt gene polymorphisms are found to nominally associate with type 2 diabetes and adiponectin levels. These data uncover a role for SMRT in mitochondrial oxidative metabolism and the aging process, which may serve as a drug target to improve health span.

6. 共生菌影响果蝇的交配偏差

【提要】
　　通常以为交配偏差是在物种形成早期就确立的事件
。该钻研通过果蝇尝试发现体内共生菌也会影响果蝇交配偏差
。通过用分歧食品喂养由统一群果蝇分成的两组，而后混合两组果蝇，发现果蝇偏差于和同组的果蝇交配，该偏差从第一代可持续至少37代
。而喂食中参与抗生素能解除这种偏差性，批注是果蝇菌群的缘故
。进一步钻研批注这些共生菌会扭转果蝇表皮的性信息素水平从而影响其交配偏差
。

【点评】
越来越多的钻研批注共生菌群对动物有着重要影响
。

【原文摘录】PNAS  DOI: 10.1073/pnas.1009906107
Commensal bacteria play a role in mating preference of Drosophila melanogaster
G. Sharon, D. Segal, J. M. Ringo, et al.
Development of mating preference is considered to be an early event in speciation. In this study, mating preference was achieved by dividing a population of Drosophila melanogaster and rearing one part on a molasses medium and the other on a starch medium. When the isolated populations were mixed, “molasses flies” preferred to mate with other molasses flies and “starch flies” preferred to mate with other starch flies. The mating preference appeared after only one generation and was maintained for at least 37 generations. Antibiotic treatment abolished mating preference, suggesting that the fly microbiota was responsible for the phenomenon. This was confirmed by infection experiments with microbiota obtained from the fly media (before antibiotic treatment) as well as with a mixed culture of Lactobacillus species and a pure culture of Lactobacillus plantarum isolated from starch flies. Analytical data suggest that symbiotic bacteria can influence mating preference by changing the levels of cuticular hydrocarbon sex pheromones. The results are discussed within the framework of the hologenome theory of evolution.