細(xì)胞老化是指細(xì)胞的復(fù)制過程不可逆轉(zhuǎn)地停止了,。研究人員發(fā)現(xiàn),，兩種對細(xì)胞分裂和復(fù)制起關(guān)鍵作用的腫瘤抑制基因左右了小鼠的衰老過程。這篇在線發(fā)表在《自然—細(xì)胞生物學(xué)》（Nature Cell Biology）期刊上的論文首次揭示了細(xì)胞老化機(jī)制和整體器官衰老間的直接聯(lián)系,。
BubR1是一種細(xì)胞分裂蛋白質(zhì),，表達(dá)出低水平BubR1的變異小鼠表現(xiàn)出早衰的特征：壽命縮短,、肌肉萎縮和脂肪喪失等,。在受影響的組織中，骨骼肌肉和脂肪中堆積了高水平的p16Ink4a和p19Arf蛋白質(zhì),。通過分析BubR1—缺失小鼠體內(nèi)p16Ink4a和p19Arf基因的失活結(jié)果,，Jan van Deursen和同事研究了這兩種基因在衰老過程中的作用。他們發(fā)現(xiàn),，清除p16Ink4a基因能減緩細(xì)胞的衰老過程,，也能減緩機(jī)體的老化過程，反之,，p19Arf的滅活會(huì)加劇這些作用,。
基于p16Ink4a和p19Arf基因表達(dá)水平隨衰老而增加的事實(shí)，以前的研究推測了這兩種腫瘤抑制基因在衰老過程中的作用,。然而,，過去的研究從未證實(shí)它們與衰老過程中的直接聯(lián)系，因?yàn)槿笔н@些基因的小鼠過早地死于腫瘤疾病,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology,，doi:10.1038/ncb1744，Darren J. Baker,，Jan M. van Deursen
Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency
Darren J. Baker1, Carmen Perez-Terzic2, Fang Jin1, Kevin Pitel1, Nicolas J. Niederländer3, Karthik Jeganathan1, Satsuki Yamada3, Santiago Reyes3, Lois Rowe3, H. Jay Hiddinga4, Norman L. Eberhardt4, Andre Terzic3 & Jan M. van Deursen1,4
AbstractExpression of p16Ink4a and p19Arf increases with age in both rodent and human tissues. However, whether these tumour suppressors are effectors of ageing remains unclear, mainly because knockout mice lacking p16Ink4aor p19Arf die early of tumours. Here, we show that skeletal muscle and fat, two tissues that develop early ageing-associated phenotypes in response to BubR1 insufficiency, have high levels of p16Ink4a and p19Arf. Inactivation of p16Ink4a in BubR1-insufficient mice attenuates both cellular senescence and premature ageing in these tissues. Conversely, p19Arfinactivation exacerbates senescence and ageing in BubR1 mutant mice. Thus, we identify BubR1 insufficiency as a trigger for activation of the Cdkn2a locus in certain mouse tissues, and demonstrate that p16Ink4a is an effector and p19Arf an attenuator of senescence and ageing in these tissues.
