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

随着年龄的增长，不幸的是，人类会屈从于各种令人衰弱的疾病，例如大脑退化、糖尿病、心脏问题和肌肉退化，仅举四例。然而，由于涉及的时间尺度，很难研究人类的衰老。为了绕过这个问题，科学家们使用了更简单的有机体，如蠕虫、苍蝇和老鼠。特别是，对线虫(拉丁名称为线虫)的研究有助于发现和理解衰老过程。例如，通过改变各种分子的活性来增加或减少蠕虫的寿命是可能的，令人惊讶的是，延长寿命的干预措施通常还可以改善动物与年龄相关的健康。因此，这些研究表明，不仅可以延长寿命，而且可以提高生活质量。由于这项研究中发现的大多数分子也存在于人类细胞中，通过研究它们对简单生物体寿命的影响，我们最终将能够利用这些信息来设计减缓衰老和改善人类晚年健康的方法。在蠕虫中，一种重要的衰老分子被称为SKN-1。它在功能上等同于人类的NRF蛋白。如果SKN-1活性降低，蠕虫的寿命就会缩短，反之，如果SKN-1活性增加，蠕虫的寿命也会缩短。因此，了解SKN-1是如何工作的，是了解衰老过程并开发干预方法的关键。SKN-1/NRF在细胞中起着非常重要的作用，因为它允许细胞对应激条件做出反应并存活下来。它对调节蛋白质的动态平衡和代谢也是非常重要的。我们想了解这些和其他功能对控制衰老是如何重要的，并且由于蠕虫中存在的SKN-1分子与人类中的分子相似，我们的工作对于更好地了解人类的衰老具有真正的相关性。目前，人们对寻找延长寿命从而改善终身健康的遗传或化学调节器非常感兴趣。我们知道SKN-1对这些过程很重要，研究它特别有趣，因为它已经是一个既定的药物靶点。因此，通过定义它的工作原理，我们将能够利用这一点来开发抗衰老疗法，从而奠定有助于促进人类长寿和健康生活的知识基础。

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.