Seluanov Andrei, Chen Zhuoxun, Hine Christopher, Sasahara Tais H C, Ribeiro Antonio A C M, Catania Kenneth C, Presgraves Daven C, Gorbunova Vera
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Aging Cell. 2007 Feb;6(1):45-52. doi: 10.1111/j.1474-9726.2006.00262.x. Epub 2006 Dec 14.
In multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.
在多细胞生物中，端粒酶对于维持生殖细胞系中的端粒长度是必需的，但在体细胞中则不是必需的。例如，小鼠在体细胞和生殖细胞系组织中都表达端粒酶，而人类几乎只在生殖细胞系中表达端粒酶。因此，当人类体细胞的端粒达到临界长度时，细胞会进入不可逆的生长停滞状态，即复制性衰老。复制性衰老被认为是一种限制细胞增殖的抗癌机制。小鼠和人类之间的这种差异导致了这样一种假说：体细胞中端粒酶的抑制是大型长寿生物中作为一种肿瘤抑制适应性进化而来的。我们通过对15种具有高度不同寿命和体重的啮齿动物物种进行比较分析，测试了端粒酶活性的调节是否与寿命和体重共同进化。在这里我们表明，端粒酶活性并非与寿命共同进化，而是与体重共同进化：体型较大的啮齿动物会抑制体细胞中的端粒酶活性。这些结果表明，相比于长寿，大体型带来的癌症风险更大，大型动物进化出端粒酶活性抑制来降低这种风险。
