哈佛科學(xué)家最近破天荒地令年老的老鼠器官獲得新生,，成功逆轉(zhuǎn)衰老過(guò)程，這項(xiàng)突破成果或有望防治腦退化癥(老人癡呆癥),、糖尿病和心臟病等疾病,，甚至有望打開永恒青春的奧秘，進(jìn)一步邁向研制“長(zhǎng)生不老藥”,。
科學(xué)雜志《自然》網(wǎng)站28日刊登美國(guó)哈佛醫(yī)學(xué)院的科研報(bào)告,，研究員飼養(yǎng)了一些經(jīng)基因改造的老鼠，令它們因缺乏“端粒”(telomerase)而未老先衰,，出現(xiàn)嗅覺衰退,、腦部縮小、不育,、腸部和脾臟受損等疾病,，使它們皮膚、大腦,、內(nèi)臟和其它器官老化,。
所謂“端粒”，是指染色體末端的DNA重復(fù)序列,，作用是保持染色體的完整性,。“端粒”的長(zhǎng)度反映著細(xì)胞復(fù)制史及復(fù)制潛能，被稱作細(xì)胞壽命的“有絲分裂鐘”,。
雄鼠恢復(fù)生育能力
報(bào)道稱,，科研人員將這些老鼠分為兩組，把一種名為“TERT”的定時(shí)釋放藥物,，植入其中一組老鼠的皮下,，重啟它們體內(nèi)休眠的“端粒”基因。
結(jié)果在短短2個(gè)月內(nèi)，有注射TERT的老鼠體內(nèi)長(zhǎng)出許多新的細(xì)胞,，主要器官運(yùn)作功能改善,，身體差不多完全“返老還童”，當(dāng)中雄性的老鼠更恢復(fù)生育功能,。實(shí)驗(yàn)鼠最終活到正常鼠的壽命,，但并不比普通鼠壽命長(zhǎng)。
進(jìn)行研究的德皮尼奧博士表示,，實(shí)驗(yàn)鼠對(duì)人類而言,，就像一個(gè)40歲的人，身體未老先衰像80多歲的老人,，而這項(xiàng)實(shí)驗(yàn)?zāi)孓D(zhuǎn)衰老過(guò)程,，把他變回50歲一般。
德皮尼奧說(shuō)：“這些是嚴(yán)重衰老的動(dòng)物,，但經(jīng)過(guò)一個(gè)月治療后,，它們已有具體康復(fù)跡象，包括腦部長(zhǎng)出新的細(xì)胞,。”他指出,，這是首次有老鼠實(shí)驗(yàn)成功把衰老過(guò)程逆轉(zhuǎn)，意味著一些老化的器官也有“重生”的可能,。
提升“端粒”水平人類患癌風(fēng)險(xiǎn)或增加
不過(guò),，要把這一科技應(yīng)用于人體身上將會(huì)較為困難，老鼠一生中都能制造端粒,，但是人類到成年后便會(huì)自動(dòng)“關(guān)掉”這種,，從而阻止細(xì)胞增長(zhǎng)失控，以免轉(zhuǎn)化成癌癥,。因此,，提升人體的“端粒”水平雖然或有助減緩衰老速度，但同時(shí)增加患癌的風(fēng)險(xiǎn),。
德皮尼奧認(rèn)為,，“TERT”療法如果是分階段進(jìn)行，和只用于身體沒有癌細(xì)胞及較為年青的人身上,，療法或?qū)θ梭w安全,。牛津大學(xué)生物化學(xué)家考克斯認(rèn)為，這項(xiàng)研究“非常重要”,，證明原則上短期恢復(fù)成人體內(nèi)的“端粒”,，能令年老的組織重生和恢復(fù)生理功能。（生物谷Bioon.com）
生物谷推薦原文出處：
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 & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
Correspondence to: Ronald A. DePinho1 Email: [email protected]
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 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 responses1. 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 interneurons2, 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 risk1, 3 and the marked reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.
