The temporal scaling of Caenorhabditis elegans ageing.
The temporal scaling of Caenorhabditis elegans ageing.
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DOI：
10.1038/nature16550
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发表时间：
2016-02-04
期刊：
影响因子：
64.8
通讯作者：
Fontana W
中科院分区：
文献类型：
--
作者：
Stroustrup N;Anthony WE;Nash ZM;Gowda V;Gomez A;López-Moyado IF;Apfeld J;Fontana W
衰老的过程使死亡的可能性越来越大，但也涉及到一个随机的方面，即使在同质的人群中，也会产生广泛的寿命分布。对这种随机行为的研究可能会将分子机制与决定寿命的衰老过程联系起来。在这里，通过从大规模人群中收集高精度的死亡率统计数据，我们观察到，干预措施多种多样，如饮食，温度，暴露于氧化应激，以及包括热休克因子hsf-1，缺氧诱导因子hif-1和胰岛素/IGF-1通路组分daf-2，age-1，和DAF-16都通过明显的时间延长或缩短来改变寿命分布。为了产生这样的时间尺度，每种干预措施必须在整个成年生活中以相同的程度改变死亡风险的所有生理决定因素。因此，秀丽隐杆线虫的器官衰老似乎涉及到生理学的各个方面，这些方面对各种干预措施作出一致的反应。通过这种方式，时间尺度确定了一个新的状态变量r（t），它控制着死亡的风险，其平均衰减动力学涉及一个单一的有效老化速率常数kr。产生时间尺度的干预只通过改变kr来影响寿命。这种干预，即使在成年早期短暂应用时，暂时改变kr，伴随着r变化率的短暂增加或减少，并对剩余寿命产生永久影响。生物体衰老动力学的存在是不变的遗传和环境背景下提供了一个新的定量框架的基础，用于评估如何以及有多少特定的分子过程有助于老化的方面，决定寿命。
The process of ageing makes death increasingly likely, but involves a random aspect that produces a wide distribution of lifespan even in homogeneous populations. The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1, the hypoxia-inducible factor hif-1, and the insulin/IGF-1 pathway components daf-2, age-1, and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r(t), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, kr. Interventions that produce temporal scaling influence lifespan exclusively by altering kr. Such interventions, when applied transiently even in early adulthood, temporarily alter kr with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and environmental contexts provides the basis for a new, quantitative framework for evaluating how and how much specific molecular processes contribute to the aspect of ageing that determines lifespan.