在本期Nature中,，三個(gè)實(shí)驗(yàn)室分別報(bào)告了一種蛋白的發(fā)現(xiàn)。該蛋白專門在干細(xì)胞中調(diào)控衰老。 這個(gè)發(fā)現(xiàn)可幫助回答一個(gè)根本問題：為什么哺乳動(dòng)物的祖先細(xì)胞隨著年齡增長會逐漸失去其分裂和生成新細(xì)胞的能力,？Norman Sharpless及其同事培育出一種剔出了腫瘤抑制因子p16 INK4a的小鼠,，該因子是細(xì)胞周期控制中涉及的一種蛋白，已知會以一種依賴于年齡的方式表達(dá),。在對該蛋白在血液,、胰腺和大腦的再生中所起作用進(jìn)行的研究中，三個(gè)小組分別發(fā)現(xiàn),，p16 INK4a不僅是一種生物標(biāo)記,，而且是衰老過程的一個(gè)促成因子。通過比較p16 INK4a在小鼠體內(nèi)表達(dá)增多或減少所產(chǎn)生的效應(yīng),，他們發(fā)現(xiàn),，p16 INK4a阻止干細(xì)胞的增殖，但只是在比較老的小鼠體內(nèi),。綜合起來,，該研究表明，p16 INK4a通過腫瘤抑制因子的行動(dòng)減少癌癥的發(fā)病,，與此同時(shí)通過降低干細(xì)胞功能對衰老做出貢獻(xiàn),。該研究還表明，2-型糖尿病也許與胰島失去再生能力有關(guān),，阻斷該蛋白在某些組織中的作用,，也許能夠抵抗衰老的某些效應(yīng),。
原始出處
Anna V. Molofsky1,4, Shalom G. Slutsky1,4, Nancy M. Joseph1, Shenghui He1, Ricardo Pardal1,3, Janakiraman Krishnamurthy2, Norman E. Sharpless2 and Sean J. Morrison1. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443, 448-452(28 September 2006) | doi:10.1038/nature05091; Received 10 April 2006; Accepted 25 July 2006; Published online 6 September 2006.
英文摘要
Mammalian ageing is associated with reduced regenerative capacity in tissues that contain stem cells1, 2. It has been proposed that this is at least partially caused by the senescence of progenitors with age3, 4; however, it has not yet been tested whether genes associated with senescence functionally contribute to physiological declines in progenitor activity. Here we show that progenitor proliferation in the subventricular zone and neurogenesis in the olfactory bulb, as well as multipotent progenitor frequency and self-renewal potential, all decline with age in the mouse forebrain. These declines in progenitor frequency and function correlate with increased expression of p16INK4a, which encodes a cyclin-dependent kinase inhibitor linked to senescence5. Ageing p16INK4a-deficient mice showed a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis, and the frequency and self-renewal potential of multipotent progenitors. p16INK4a deficiency did not detectably affect progenitor function in the dentate gyrus or enteric nervous system, indicating regional differences in the response of neural progenitors to increased p16INK4a expression during ageing. Declining subventricular zone progenitor function and olfactory bulb neurogenesis during ageing are thus caused partly by increasing p16INK4a expression.
