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

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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.