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玛土撒拉的动物园:自然如何为我们提供延长人类健康寿命的线索。

Methusaleh's Zoo: how nature provides us with clues for extending human health span.

作者信息

Austad S N

机构信息

University of Texas Health Science Center San Antonio, Barshop Institute for Longevity and Aging Studies, Department of Cellular and Structural Biology, 15355 Lambda Drive, STCBM Rm. 3.100, San Antonio, TX 78245, USA.

出版信息

J Comp Pathol. 2010 Jan;142 Suppl 1(Suppl 1):S10-21. doi: 10.1016/j.jcpa.2009.10.024. Epub 2009 Dec 4.

Abstract

As impressive as the accomplishments of modern molecular biologists have been in finding genetic alterations that lengthen life in short-lived model organisms, they pale in comparison to the remarkable diversity of lifespans produced by evolution. Some animal species are now firmly documented to live for more than four centuries and even some mammals, like the bowhead whale, appear to survive 200 years or more. Another group of species may not be as absolutely long-lived, but they are remarkably long-lived for their body size and metabolic rate. These species include a number of bats, some of which live for at least 40 years in the wild, as well as the naked mole-rat, which is the same size, but lives nearly 10 times as long as the laboratory mouse. Together these exceptionally long-lived organisms have important roles to play in our future understanding of the causal mechanisms and modulation of ageing. Bats and naked mole-rats in particular have already contributed in the following ways: (1) they have contributed to the abandonment of the rate-of-living theory and weakened enthusiasm for the oxidative stress hypothesis of ageing, (2) they have helped evaluate how the tumour-suppressing role of cellular senescence is affected by the evolution of diverse body sizes as well as diverse longevities, (3) they have shed light on the relationship between specific types of DNA repair and ageing and (4) they have yielded insight into new processes, specifically the maintenance of the proteome and hypotheses concerning how evolution shapes ageing. The continuing acceleration of progress in genome sequencing and development of more and more cross-species investigatory techniques will facilitate even more contributions of these species in the near future.

摘要

尽管现代分子生物学家在发现能延长短命模式生物寿命的基因改变方面取得了令人瞩目的成就,但与进化产生的显著寿命多样性相比,这些成就就显得逊色了。现在有确凿记录表明,一些动物物种能活四个多世纪,甚至一些哺乳动物,如弓头鲸,似乎能存活200年或更久。另一类物种可能并非绝对长寿,但就其体型和代谢率而言,它们的寿命却非常长。这些物种包括一些蝙蝠,其中一些在野外能活到至少40岁,还有裸鼹鼠,它与实验室小鼠体型相同,但寿命几乎是实验室小鼠的10倍。这些超长寿命的生物在我们未来对衰老因果机制和调控的理解中将发挥重要作用。特别是蝙蝠和裸鼹鼠已经在以下方面做出了贡献:(1)它们促使人们摒弃了生活率理论,并削弱了对衰老氧化应激假说的热情;(2)它们有助于评估细胞衰老的肿瘤抑制作用是如何受到不同体型和不同寿命进化的影响;(3)它们揭示了特定类型的DNA修复与衰老之间的关系;(4)它们让人们深入了解了新的过程,特别是蛋白质组的维持以及关于进化如何塑造衰老的假说。基因组测序进展的持续加速以及越来越多跨物种研究技术的发展,将在不久的将来促进这些物种做出更多贡献。

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