Quantitative analysis of a C. elegans TGF-beta and insulin circuit that links food to lifespan

衰老受到食物暴露的影响。不同的食物水平可以延长或缩短寿命，但体内的生理信号如何调节这些影响尚不清楚。我们的目标是了解神经系统中特定激素的水平如何随着食物水平的不同而变化，并将这些激素的变化与食物引起的寿命变化联系起来。特别是，我们想要确定一种激素是如何作为信号来调节其他激素的活动的，而这些激素又反过来调节衰老过程。通过研究这些激素之间的基因调控，我们可以了解这些激素在调节动物不同部位之间的交流中所起的作用，了解这些激素传递的食物水平信息，以及它们所采取的途径。我们还将了解特定激素的水平与不同食物水平的关系，这将揭示动物如何区分不同的食物水平，并利用神经系统中的这些激素来调节它们的生理。要详细研究这些交流过程，需要对许多活体动物体内的激素水平进行非常精确的测量。此外，为了了解这些通信在调节衰老中的作用，我们需要测量许多动物的寿命。蛔虫模型非常适合这些实验，因为它使用与人类相似的激素来调节其寿命。这种蛔虫只能活几个星期，因此我们可以很快地完成寿命测量，而其他动物可以活几个月、几年甚至几十年。此外，在这种蛔虫身上有许多实验工具，使我们能够测量和操纵活体动物的激素水平。这些工具在其他实验模型中并不总是可用的。因此，我们可以研究改变一种激素对其他激素和寿命的影响。我们的实验室有两台显微镜，配有定制的计算机化系统，每小时可以检查100只蛔虫。这种自动化系统加快了我们的实验速度，使我们能够比手工方法更详细地检查激素活性。我们是欧洲唯一拥有这种显微镜系统的实验室，因为我们与设计它的工程师合作。这种蛔虫在衰老研究中有着非常强大的记录，一些与人类衰老有关的基因是基于对这种蛔虫的发现而确定的。从这项工作中，我们期望发现关于调节食物对寿命的激素途径的新知识。从长远来看，这些知识可以帮助我们了解人类对食物的生理反应，从而有助于优化人类健康饮食，并为改善不健康饮食的负面影响提供途径。

Ageing is affected by exposure to food. Different food levels can either increase or decrease lifespan, but how physiological signals within the body mediate these effects is not clear. Our goal is to understand how the levels of specific hormones from the nervous system change in response to different food levels, and relate these hormonal changes to the changes in lifespan elicited by food. In particular, we want to determine how one hormone could serve as a signal to regulate the activity of other hormones, which in turn modulate the ageing process. By studying the genetic regulation between these hormones, we can understand the role of these hormones in mediating communication between different parts of an animal, the information about the food level that these hormones transmitted, and the routes they take. We will also learn about how the levels of specific hormones are related to different food levels, which will reveal how well animals could distinguish between different food levels to modulate their physiology using these hormones from the nervous system.To study these processes of communication in detail requires very accurate measurements of the hormone levels in many live animals. Furthermore, to understand the role of these communications in modulating ageing, we need to measure the lifespan of many animals. The roundworm model is ideally suited for these experiments, because it uses similar hormones as humans to modulate its lifespan. This roundworm lives for only a few weeks, thus we can complete our lifespan measurements quickly, in contrast to other animals that could live for months, years or decades. Moreover, there are many experimental tools in this roundworm that allows us to measure and manipulate hormone levels in live animals. Such tools are not always available in other experimental models. We can therefore examine the effects of changing one hormone on other hormones and on lifespan. Our lab has two microscopes with custom-made computerised systems that allows us to examine a hundred roundworms an hour. This automated system speeds up our experiments and allows us to examine the hormone activity in greater detail than is possible by manual methods. We are the only lab in Europe with such a microscope system, due to our collaboration with the engineers that designed it. This roundworm has a very strong track record in ageing research, and several genes involved in human ageing were identified based on discoveries in this roundworm.From this work, we expect to uncover new knowledge about the hormonal pathways that modulate lifespan in response to food. In the long term, this knowledge can help us understand the physiological responses to food in humans, which in turn can help optimise diets for human health and provide avenues to ameliorate the negative effects of unhealthy diets.