Gorbunova Vera, Seluanov Andrei
Department of Biology, University of Rochester, Rochester, NY 14627, USA.
Mech Ageing Dev. 2009 Jan-Feb;130(1-2):3-9. doi: 10.1016/j.mad.2008.02.008. Epub 2008 Feb 23.
Telomerase is repressed in the majority of human somatic tissues. As a result human somatic cells undergo replicative senescence, which plays an important role in suppressing tumorigenesis, and at the same time contributes to the process of aging. Repression of somatic telomerase activity is not a universal phenomenon among mammals. Mice, for example, express telomerase in somatic tissues, and mouse cells are immortal when cultured at physiological oxygen concentration. What is the status of telomerase in other animals, beyond human and laboratory mouse, and why do some species evolve repression of telomerase activity while others do not? Here we discuss the data on telomere biology in various mammalian species, and a recent study of telomerase activity in a large collection of wild rodent species, which showed that telomerase activity coevolves with body mass, but not lifespan. Large rodents repress telomerase activity, while small rodents maintain high levels of telomerase activity in somatic cells. We discuss a model that large body mass presents an increased cancer risk, which drives the evolution of telomerase suppression and replicative senescence.
端粒酶在大多数人类体细胞组织中受到抑制。因此，人类体细胞会经历复制性衰老，这在抑制肿瘤发生中起重要作用，同时也促成了衰老过程。体细胞端粒酶活性的抑制在哺乳动物中并非普遍现象。例如，小鼠在体细胞组织中表达端粒酶，并且在生理氧浓度下培养时，小鼠细胞是永生的。除了人类和实验室小鼠之外，其他动物中端粒酶的状况如何？为什么有些物种进化出对端粒酶活性的抑制，而其他物种却没有？在这里，我们讨论了各种哺乳动物物种中端粒生物学的数据，以及最近对大量野生啮齿动物物种端粒酶活性的研究，该研究表明端粒酶活性与体重共同进化，但与寿命无关。大型啮齿动物抑制端粒酶活性，而小型啮齿动物在体细胞中维持高水平的端粒酶活性。我们讨论了一个模型，即大体型会增加癌症风险，这推动了端粒酶抑制和复制性衰老的进化。
