The environmental drivers of senescence: an experimental test in the wild

衰老的环境驱动因素：野外实验测试

• 批准号: NE/X001423/1
• 负责人: Tom Little
• 金额: $ 85.38万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FX001423%2F1
• 关键词: environmental; drivers; senescence; experimental; test

Age predicts many things about our health, including which infections we might have, our risk of dying from these infections, or which chronic diseases we are at risk from. Some individuals present an even greater risk, because they are ageing very fast, or are 'grey before their time'. But why? In humans, we have some answers: lifestyle, reproduction and infections appear to accelerate ageing. We know much less about what drives ageing and senescence in wild animals, but if we could identify the factors that cause rapid ageing in the wild, we could predict which individuals and populations are at risk.Recently, a biomarker of age has been developed that can be used on wild animals. This technology is like rings in tree trunks, but is based on the observation that molecules called methyl groups gradually accumulate on DNA as individuals age. The number of these methyl groups turns out to accurately reflect chronological age. Importantly, individuals who are ageing rapidly have the highest methyl group counts. This study aims to identify environmental factors that cause some wild individuals to accumulate more methyl groups on their DNA. This phenomenon is named an "Epigenetic Clock", so put another way, we want to determine why some individuals have a fast-ticking clock, but others have a slow clicking clock, and so are likely to live longer. To understand the causes of rapid ageing, it is immensely helpful to study an animal on which we can do simple yet powerful experiments. That is why we propose to study methylation in the wood mouse - an easily-captured wild mouse where we can conduct controlled experiments in the field to modify key stressors and measure their impact on the ageing rate. We will provide high quality food or drug treat (to control parasites) to half of the mice in our field locations, leaving the rest as untreated controls. To measure methylation, we will use an exciting new technology known as the multi-species methylation array that has already proven itself highly effective in other mammals. Our results will allow a better understanding of if and how nutrition and infection changes methylation to cause individuals to age faster or slower than expected. Because nutrition and infection are important to almost any animal, our work will be of interest to many researchers in ecology and 'healthy ageing' research. This will be one of the first large-scale deployments of an epigenetic clock to a wild animal, and certainly the first wild-experimental manipulation of stressors and their knock-on effects on the ageing rate.

年龄可以预测我们健康的许多方面，包括我们可能会感染哪些疾病，我们死于这些感染的风险，或者我们面临哪些慢性疾病的风险。有些人的风险更大，因为他们衰老得很快，或者“过早地变老”。但为什么呢？在人类中，我们有一些答案：生活方式，生殖和感染似乎会加速衰老。我们对野生动物衰老和衰老的驱动因素知之甚少，但如果我们能够确定导致野生动物快速衰老的因素，我们就可以预测哪些个体和种群处于危险之中。最近，已经开发出一种可用于野生动物的年龄生物标志物。这项技术就像树干上的年轮，但它是基于这样的观察：随着个体年龄的增长，被称为甲基的分子会逐渐积累在DNA上。这些甲基的数量准确地反映了实际年龄。重要的是，快速老化的个体具有最高的甲基数量。这项研究旨在确定导致一些野生个体在DNA上积累更多甲基的环境因素。这种现象被命名为“表观遗传时钟”，所以换句话说，我们想确定为什么有些人有一个快速滴答的时钟，而另一些人有一个缓慢滴答的时钟，所以可能活得更长。为了了解快速衰老的原因，研究一种动物是非常有帮助的，我们可以在它身上做简单而强大的实验。这就是为什么我们建议研究木鼠中的甲基化-一种容易捕获的野生小鼠，我们可以在现场进行受控实验，以修改关键的压力源并测量它们对衰老率的影响。我们将提供高质量的食物或药物治疗（以控制寄生虫），以一半的小鼠在我们的领域的位置，留下其余的作为未经处理的控制。为了测量甲基化，我们将使用一种令人兴奋的新技术，称为多物种甲基化阵列，该技术已在其他哺乳动物中证明非常有效。我们的研究结果将使我们更好地了解营养和感染是否以及如何改变甲基化，从而导致个体比预期更快或更慢地衰老。由于营养和感染对几乎任何动物都很重要，我们的工作将引起许多生态学和“健康老龄化”研究人员的兴趣。这将是第一次将表观遗传时钟大规模部署到野生动物身上，当然也是第一次对压力源及其对衰老率的连锁反应进行野生实验操作。