Deciphering the tissue-specific role of the transcription factor SKN-1B in C. elegans to promote a long and healthy life.

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With age, it is unfortunate that humans succumb to a variety of debilitating conditions e.g. brain degeneration, diabetes, heart problems and muscle degeneration to name but four. However, it is difficult to study ageing in humans due to the time scales involved. To circumvent this problem, scientists use simpler organisms such as worms, flies and mice. In particular, studies with a nematode worm (Latin name C. elegans) have been instrumental to discovering and understanding the ageing process. For example, it is possible to increase or decrease lifespan in worms by altering the activity of various molecules and amazingly, interventions that extend lifespan often also improve the age-related health of the animals. Thus, these studies have shown that it is possible not only to extend lifespan but also the quality of life. As most of the molecules identified in this research are also present in human cells, by studying their effects on lifespan in simple organisms, we will eventually be able to use this information to design approaches to slow ageing and improve the late-life health of humans.In worms, one important ageing molecule is called SKN-1. It is equivalent (in terms of its function) to the human Nrf proteins. If SKN-1 activity is decreased then worms have a shorter lifespan and, conversely if SKN-1 activity is increased so is their lifespan. Understanding how SKN-1 works is therefore key to understanding the ageing process and developing ways to intervene in it. SKN-1/Nrf has a very important role in cells because it allows them to respond to and survive stressful conditions. It is also very important for regulating protein homeostasis and metabolism. We want to understand how these and other functions are important for controlling ageing and as the SKN-1 molecules present in worms are similar to those in humans, our work has real relevance to a better understanding of human ageing.There is currently considerable interest in identifying genetic or chemical modulators to extend lifespan and thus improve lifelong health. We know that SKN-1 is important for these processes and, it is particularly interesting to study as it is already an established drug target. So, by defining how it works we will be able to harness this to develop anti-ageing therapies and therefore lay the foundations of knowledge that will be useful for promoting long and healthy human lives.