Matheu Ander, Maraver Antonio, Klatt Peter, Flores Ignacio, Garcia-Cao Isabel, Borras Consuelo, Flores Juana M, Viña Jose, Blasco Maria A, Serrano Manuel
Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Nature. 2007 Jul 19;448(7151):375-9. doi: 10.1038/nature05949.
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.
由Cdkn2a基因座的可变阅读框蛋白（Arf）和p53（也称为Trp53）形成的肿瘤抑制途径在细胞损伤的检测和消除中起核心作用，这构成了其强大的癌症保护活性的基础。与癌症类似，衰老也是由损伤积累导致的，因此，我们推测Arf/p53可能通过减轻与衰老相关的损伤负荷而具有抗衰老活性。在这里，我们表明，经过基因操作使Arf和p53水平升高但其他方面正常调节的小鼠具有很强的抗癌能力，且与衰老相关的损伤水平降低。这些观察结果将Arf/p53的保护作用扩展到了衰老领域，揭示了一种以前未知的抗衰老机制，并为抗癌能力和长寿的共同进化提供了理论依据。
