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破解衰老:一种利用医学研究大数据延长人类寿命的策略。

Hacking Aging: A Strategy to Use Big Data From Medical Studies to Extend Human Life.

作者信息

Fedichev Peter O

机构信息

Gero LLC, Moscow, Russia.

Moscow Institute of Physics and Technology, Moscow, Russia.

出版信息

Front Genet. 2018 Oct 23;9:483. doi: 10.3389/fgene.2018.00483. eCollection 2018.

Abstract

Age is the most important single factor associated with chronic diseases and ultimately, death. The mortality rate in humans doubles approximately every eight years, as described by the Gompertz law of mortality. The incidence of specific diseases, such as cancer or stroke, also accelerates after the age of about 40 and doubles at a rate that mirrors the mortality-rate doubling time. It is therefore, entirely plausible to think that there is a single underlying process, the driving force behind the progressive reduction of the organism's health leading to the increased susceptibility to diseases and death; aging. There is, however, no fundamental law of nature requiring exponential morbidity and mortality risk trajectories. The acceleration of mortality is thus the most important characteristics of the aging process. It varies dramatically even among closely related mammalian species and hence appears to be a tunable phenotype. Here, we follow how big data from large human medical studies, and analytical approaches borrowed from physics of complex dynamic systems can help to reverse engineer the underlying biology behind Gompertz mortality law. With such an approach we hope to generate predictive models of aging for systematic discovery of biomarkers of aging followed by identification of novel therapeutic targets for future anti-aging interventions.

摘要

年龄是与慢性疾病乃至最终死亡相关的最重要的单一因素。正如冈珀茨死亡率定律所描述的那样,人类的死亡率大约每八年就会翻一番。特定疾病(如癌症或中风)的发病率在40岁左右之后也会加速上升,并且以与死亡率翻倍时间相同的速度翻倍。因此,认为存在一个单一的潜在过程,即导致机体健康逐渐下降、疾病易感性增加和死亡的驱动力——衰老,是完全合理的。然而,并没有自然基本定律要求发病率和死亡率呈指数增长轨迹。因此,死亡率的加速上升是衰老过程最重要的特征。即使在亲缘关系密切的哺乳动物物种之间,这种加速上升也存在巨大差异,因此似乎是一种可调节的表型。在这里,我们将探讨来自大型人类医学研究的大数据以及从复杂动态系统物理学借鉴的分析方法如何有助于逆向工程冈珀茨死亡率定律背后的潜在生物学机制。通过这种方法,我们希望生成衰老预测模型,以便系统地发现衰老生物标志物,随后确定未来抗衰老干预的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e305/6206166/ad907850f24c/fgene-09-00483-g0001.jpg

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