细胞老化是指细胞的复制过程不可逆转地停止了。研究人员发现，两种对细胞分裂和复制起关键作用的肿瘤抑制基因左右了小鼠的衰老过程。这篇在线发表在《自然—细胞生物学》（Nature Cell Biology）期刊上的论文首次揭示了细胞老化机制和整体器官衰老间的直接联系。
BubR1是一种细胞分裂蛋白质，表达出低水平BubR1的变异小鼠表现出早衰的特征：寿命缩短、肌肉萎缩和脂肪丧失等。在受影响的组织中，骨骼肌肉和脂肪中堆积了高水平的p16Ink4a和p19Arf蛋白质。通过分析BubR1—缺失小鼠体内p16Ink4a和p19Arf基因的失活结果，Jan van Deursen和同事研究了这两种基因在衰老过程中的作用。他们发现，清除p16Ink4a基因能减缓细胞的衰老过程，也能减缓机体的老化过程，反之，p19Arf的灭活会加剧这些作用。
基于p16Ink4a和p19Arf基因表达水平随衰老而增加的事实，以前的研究推测了这两种肿瘤抑制基因在衰老过程中的作用。然而，过去的研究从未证实它们与衰老过程中的直接联系，因为缺失这些基因的小鼠过早地死于肿瘤疾病。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
