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

破译转录因子 SKN-1B 在秀丽隐杆线虫中的组织特异性作用，以促进长寿和健康的生活。

• 批准号: BB/R003629/1
• 负责人: Jennifer Tullet
• 金额: $ 58.43万
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR003629%2F1
• 关键词: Deciphering; tissue; specific; role; transcription

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.

随着年龄的增长，不幸的是，人类屈服于各种令人衰弱的条件，例如脑退化，糖尿病，心脏问题和肌肉变性，只有四个。但是，由于涉及的时间尺度，很难研究人类的衰老。为了解决这个问题，科学家使用了更简单的生物，例如蠕虫，苍蝇和小鼠。特别是，使用线虫蠕虫（拉丁名字秀丽隐杆线虫）的研究对发现和理解衰老过程起着重要作用。例如，通过改变各种分子的活性以及延长寿命的干预措施通常也可以改善动物的年龄相关健康，可以通过改变各种分子的活性来增加或降低蠕虫的寿命。因此，这些研究表明，不仅有可能延长寿命，还可以延长生活质量。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中寿命的影响，我们最终将能够使用这些信息来设计减慢衰老并改善人类后期健康的方法。在蠕虫中，一个重要的衰老分子称为SKN-1。它与人NRF蛋白相当（就其功能而言）。如果SKN-1活性降低，则蠕虫的寿命较短，相反，如果SKN-1活性增加，那么它们的寿命也是如此。因此，了解SKN-1的工作原理是了解衰老过程和开发干预方法的关键。 SKN-1/NRF在细胞中具有非常重要的作用，因为它使它们能够响应并在压力条件下生存。这对于调节蛋白质稳态和代谢也非常重要。我们想了解这些功能和其他功能对于控制衰老至关重要，并且由于蠕虫中存在的SKN-1分子与人类相似，因此我们的工作与对人类年龄的更好理解具有真正的相关性。目前，人们对识别遗传或化学调节剂的兴趣非常兴趣，从而延长了寿命，从而改善了寿命健康。我们知道SKN-1对于这些过程很重要，并且研究它已经是一个既定的药物靶标，这一点特别有趣。因此，通过定义它的工作原理，我们将能够利用这种工作来开发抗衰老疗法，从而奠定知识基础，这些基础对于促进长期健康的人类生活非常有用。

项目成果

Interplay of mitochondrial fission-fusion with cell cycle regulation: Possible impacts on stem cell and organismal aging.

• DOI: 10.1016/j.exger.2020.110919
• 发表时间: 2020-07-01
• 期刊: Experimental gerontology
• 影响因子: 3.9
• 作者: Spurlock B;Tullet J;Hartman JL 4th;Mitra K
• 通讯作者: Mitra K

Signal Transduction Pathways in Ageing.

衰老中的信号转导途径。

• DOI: 10.1007/978-981-13-2835-0_11
• 发表时间: 2018
• 期刊: Sub-cellular biochemistry
• 作者: Slack C

Neuronal SKN-1B modulates nutritional signalling pathways and mitochondrial networks to control satiety.

• DOI: 10.1371/journal.pgen.1009358
• 发表时间: 2021-03
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Tataridas-Pallas N;Thompson MA;Howard A;Brown I;Ezcurra M;Wu Z;Silva IG;Saunter CD;Kuerten T;Weinkove D;Blackwell TK;Tullet JMA
• 通讯作者: Tullet JMA