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首页> 外文期刊>Biochemistry >Telomere Biology: Cancer Firewall or Aging Clock?
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Telomere Biology: Cancer Firewall or Aging Clock?

机译：端粒生物学：癌症防火墙还是时钟老化？

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It has been a decade since the first surprising discovery that longer telomeres in humans are statistically associated with longer life expectancies. Since then, it has been firmly established that telomere shortening imposes an individual fitness cost in a number of mammalian species, including humans. But telomere shortening is easily avoided by application of telomerase, an enzyme which is coded into nearly every eukaryotic genome, but whose expression is suppressed most of the time. This raises the question how the sequestration of telomerase might have evolved. The predominant assumption is that in higher organisms, shortening telomeres provide a firewall against tumor growth. A more straightforward interpretation is that telomere attrition provides an aging clock, reliably programming lifespans. The latter hypothesis is routinely rejected by most biologists because the benefit of programmed lifespan applies only to the community, and in fact the individual pays a substantial fitness cost. There is a long-standing skepticism that the concept of fitness can be applied on a communal level, and of group selection in general. But the cancer hypothesis is problematic as well. Animal studies indicate that there is a net fitness cost in sequestration of telomerase, even when cancer risk is lowered. The hypothesis of protection against cancer has never been tested in animals that actually limit telomerase expression, but only in mice, whose lifespans are not telomerase-limited. And human medical evidence suggests a net aggravation of cancer risk from the sequestration of telomerase, because cells with short telomeres are at high risk of neoplastic transformation, and they also secrete cytokines that exacerbate inflammation globally. The aging clock hypothesis fits well with what is known about ancestral origins of telomerase sequestration, and the prejudices concerning group selection are without merit. If telomeres are an aging clock, then telomerase makes an attractive target for medical technologies that seek to expand the human life- and health-spans.
机译：自从第一个令人惊讶的发现以来，已经有十年了，从统计学上讲，人类更长的端粒与更长的预期寿命相关。从那时起，就已经牢固地确定，端粒缩短会给包括人类在内的许多哺乳动物增加个体的适应能力。但是端粒酶的缩短很容易通过应用端粒酶来避免，端粒酶是一种编码到几乎每个真核生物基因组中的酶，但是其表达在大多数情况下都受到抑制。这就提出了一个问题，即端粒酶的隔离可能如何发展。主要假设是，在高等生物中，缩短端粒可提供阻止肿瘤生长的防火墙。更为直接的解释是端粒磨损会导致时钟老化，从而可靠地编程寿命。后一种假设被大多数生物学家常规拒绝，因为计划寿命的好处仅适用于社区，实际上，个人为此付出了可观的健身费用。长期以来，人们一直怀疑健身的概念可以在社区层面上应用，并且通常可以在群体选择上应用。但是癌症假说也有问题。动物研究表明，即使降低了癌症风险，在隔离端粒酶中也存在净健身成本。从未在实际上限制端粒酶表达的动物中测试过针对癌症的保护这一假设，但仅在寿命不受端粒酶限制的小鼠中进行了测试。而且人类医学证据表明，端粒酶的隔离会导致患癌症的风险加重，因为端粒短的细胞处于肿瘤转化的高风险中，并且它们还会分泌会加剧炎症的细胞因子。时钟老化的假设与端粒酶螯合的祖先起源非常吻合，并且关于群体选择的偏见也没有根据。如果端粒是一个老化的时钟，那么端粒酶将成为寻求扩大人类寿命和健康寿命的医疗技术的诱人靶标。

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