來自中科院上海生命科學(xué)研究院生化與細(xì)胞所,，廣州生物醫(yī)藥與健康研究院等處的研究人員發(fā)表了題為“Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells”的文章,，發(fā)現(xiàn)Rapamycin等抗衰老藥物可以提高小鼠細(xì)胞重編程的效率，這說明生物體壽命的調(diào)節(jié)和細(xì)胞重編程過程的調(diào)控之間可能有著功能上的緊密聯(lián)系,，這一研究成果公布在國際著名期刊《衰老細(xì)胞》（Aging Cell）上,，這一研究課題獲得國家科技部973項目、國家自然科學(xué)基金委以及中國科學(xué)院干細(xì)胞先導(dǎo)專項的經(jīng)費(fèi)資助,。
領(lǐng)導(dǎo)這一研究的是中科院裴鋼研究員,，裴鋼研究組近年來在iPS細(xì)胞研究方面獲得了一些重要的成果，主要集中在iPS細(xì)胞誘導(dǎo)效率方面,，之前他們曾發(fā)文,，發(fā)現(xiàn)小分子化合物通過E-cadherin蛋白能加速重編程過程，為提高iPS細(xì)胞誘導(dǎo)效率提供了一種新策略,。裴鋼研究員為中國科學(xué)院院士,、第三世界科學(xué)院院士，曾先后獲得過求是科技基金會“杰出青年學(xué)者獎”,、何梁何利科技進(jìn)步獎,、國家自然科學(xué)二等獎、上海市自然科學(xué)一等獎,。
生物體的衰老（aging）是一個非常復(fù)雜的過程,。隨著年齡的增長，生物體內(nèi)各種分子,、細(xì)胞,、組織以及器官的損傷會不斷的積累，從而逐漸喪失功能,，并最終導(dǎo)致疾病和死亡,。近年來，延緩衰老以及延長人類的健康壽命（healthy lifespan）成為了生物學(xué)研究的熱點(diǎn),。包括mTOR以及IIS 信號通路在內(nèi)的一些細(xì)胞信號通路已經(jīng)被證明與生物體的壽命調(diào)節(jié)有著密切的聯(lián)系,。生化與細(xì)胞所裴鋼課題組最近的一項研究表明，生物體壽命的調(diào)節(jié)和細(xì)胞重編程過程的調(diào)控之間可能有著功能上的緊密聯(lián)系。
Rapamycin是一種臨床使用的免疫抑制劑,，并通過抑制mTOR信號通路而調(diào)節(jié)細(xì)胞的存活,，增殖，以及遷移等,。在包括小鼠、果蠅,、線蟲等在內(nèi)的多種模式生物上,，rapamycin已被證明能夠顯著延長生物體的壽命。
在最近的研究中,，裴鋼研究組發(fā)現(xiàn),，在小鼠細(xì)胞重編程的早期給以rapamycin或另一mTOR信號通路的抑制劑pp242處理都能顯著提高重編程的效率。同時,，另一與生物體壽命密切相關(guān)的通路IIS信號通路的抑制劑PQ401 也同時具有提高細(xì)胞重編程效率和延長果蠅壽命這兩種作用,。進(jìn)一步的研究發(fā)現(xiàn)，包括sirtuin蛋白的激動劑resveratrol, 以及autophagy的激活劑spermidine在內(nèi)的多種抗衰老藥物都可以有效提高細(xì)胞重編程的效率,。這些研究結(jié)果表明細(xì)胞重編程的調(diào)節(jié)和生物體壽命的調(diào)控之間共享一些信號通路,，從而提供了一種從細(xì)胞重編程的角度研究生物體壽命調(diào)節(jié)的新方法。通過解析體內(nèi)細(xì)胞重編程的過程,，科學(xué)家有可能最終獲得抵御衰老永葆青春的方法,。（生物谷Bioon.com）
生物谷推薦原文出處：
Aging Cell DOI： 10.1111/j.1474-9726.2011.00722.x
Rapamycin and other longevity‐promoting compounds enhance the generation of mouse induced pluripotent stem cells
Chen, Taotao; Shen, Li; Yu, Jie; Wan, Hongjiang; Guo, Ao; Chen, Jiekai; Long, Yuan; Zhao, Jian; Pei, Gang
Keywords:longevity;drosophila;rapamycin;induced pluripotent stem cellsSummaryReprogramming of somatic cells to a pluripotent state was first accomplished using retroviral vectors for transient expression of pluripotency‐associated transcription factors. This seminal work was followed by numerous studies reporting alternative (noninsertional) reprogramming methods and various conditions to improve the efficiency of reprogramming. These studies have contributed little to an understanding of global mechanisms underlying reprogramming efficiency. Here we report that inhibition of the mammalian target of rapamycin (mTOR) pathway by rapamycin or PP242 enhances the efficiency of reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the insulin/IGF‐1 signaling pathway, which like mTOR is involved in control of longevity, also enhances reprogramming efficiency. In addition, the small molecules used to inhibit these pathways also significantly improved longevity in Drosophila melanogaster. We further tested the potential effects of six other longevity‐promoting compounds on iPSC induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3‐kinase) inhibitor (LY294002), an antioxidant (curcumin), and an activating adenosine monophosphate‐activated protein kinase activator (metformin). With the exception of metformin, all of these chemicals promoted somatic cell reprogramming, though to different extents. Our results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a new approach for studying aging and longevity based on the regulation of cellular reprogramming.
