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楼主  发表于: 2010-12-24 19:33

 Nature:端粒酶的活化成功逆转未老先衰实验鼠衰老过程

Nature:端粒酶的活化成功逆转未老先衰实验鼠衰老过程生物谷分享      | 收藏      【 大  中  小】18

哈佛科学家最近破天荒地令年老的老鼠器官获得新生,成功逆转衰老过程,这项突破成果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,进一步迈向研制“长生不老药”。

科学杂志《自然》网站28日刊登美国哈佛医学院的科研报告,研究员饲养了一些经基因改造的老鼠,令它们因缺乏“端粒”(telomerase)而未老先衰,出现嗅觉衰退、脑部缩小、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”,是指染色体末端的DNA重复序列,作用是保持染色体的完整性。“端粒”的长度反映着细胞史及潜能,被称作细胞寿命的“有丝分裂钟”。

雄鼠恢复生育能力

报道称,科研人员将这些老鼠分为两组,把一种名为“TERT”的定时释放药物,植入其中一组老鼠的皮下,重启它们体内休眠的“端粒”基因。

结果在短短2个月内,有注射TERT的老鼠体内长出许多新的细胞,主要器官运作功能改善,身体差不多完全“返老还童”,当中雄性的老鼠更恢复生育功能。实验鼠最终活到正常鼠的寿命,但并不比普通鼠寿命长。



进行研究的德皮尼奥博士表示,实验鼠对人类而言,就像一个40岁的人,身体未老先衰像80多岁的老人,而这项实验逆转衰老过程,把他变回50岁一般。

德皮尼奥说:“这些是严重衰老的动物,但经过一个月治疗后,它们已有具体康复迹象,包括脑部长出新的细胞。”他指出,这是首次有老鼠实验成功把衰老过程逆转,意味着一些老化的器官也有“重生”的可能。

提升“端粒”水平人类患癌风险或增加

不过,要把这一科技应用于人体身上将会较为困难,老鼠一生中都能制造端粒,但是人类到成年后便会自动“关掉”这种,从而阻止细胞增长失控,以免转化成癌症。因此,提升人体的“端粒”水平虽然或有助减缓衰老速度,但同时增加患癌的风险。

德皮尼奥认为,“TERT”疗法如果是分阶段进行,和只用于身体没有癌细胞及较为年青的人身上,疗法或对人体安全。牛津大学生物化学家考克斯认为,这项研究“非常重要”,证明原则上短期恢复成人体内的“端粒”,能令年老的组织重生和恢复生理功能。(生物谷Bioon.com)

生物谷推荐原文出处:

Nature | doi:10.1038/nature09603

Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

Mariela Jaskelioff1, Florian L. Muller1, Ji-Hye Paik1, Emily Thomas1, Shan Jiang1, Andrew C. Adams2, Ergun Sahin1, Maria Kost-Alimova1, Alexei Protopopov1, Juan Cadiñanos1, James W. Horner1, Eleftheria Maratos-Flier2 & Ronald A. DePinho1

Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
Division of Endocrinology, Diabetes & Metaboli, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Correspondence to: Ronald A. DePinho1 Email: ron_depinho@dfci.harvard.edu


Abstract
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 organial 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 responses1. Here, we sought to determine whether entrenched multi-system degeneration in 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-hydroxy (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 interneurons2, this wave of telomerase-dependent neurogenesis resulted in alleviation of hypoia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk1, 3 and the marked reversal of systemic degenerative phenotypes in mice observed here support the development of regenerative strategies designed to restore telomere integrity.

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1楼  发表于: 2012-11-01 08:46
看看了,,。。。
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2楼  发表于: 2012-11-17 09:58
谢谢分享
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