How food speaks to you: A new brain-gut axis for lifelong health.

食物如何与你对话：终身健康的新脑肠轴。

• 批准号: BB/X015106/1
• 负责人: Rebecca Taylor
• 金额: $ 54.81万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX015106%2F1
• 关键词: How; food; speaks; new; brain

What we eat has a major impact on our lifelong health. Being overweight causes multiple diseases, the severity of which is exacerbated by age. This makes understanding how diet impacts the ageing process, and finding ways to manipulate it, an important priority for research and public health policy. Nutrition is a known modulator of longevity. It is possible to increase lifespan and improve age-related health by modulating food intake eg. dietary restriction or intermittent fasting, or even by simply smelling changes in nutrient levels. This project investigates what connects the sensing of nutrition by the brain with changes to other metabolic tissues like the gut (henceforth referred to as the brain-gut axis), and links this to eating behaviours, metabolic health, and ageing. Identifying new molecular targets implicated in the nutrition-brain-gut response provides tangible methods to treat age-associated pathologies and improve health. Recently the Taylor and Tullet labs independently identified and published two compelling candidate pathways that connect nutrient perception to age-related health. These are the NF-E2 related transcription factor (Nrf) and the Unfolded Protein Response (UPR) of the endoplasmic reticulum (ER). This collaborative grant brings together our past work and new preliminary data to complete the picture. We hypothesise that Nrf acts in neurons to communicate information about diet and regulate UPR activation in the gut. This sequence of events will then control nutrient regulated feeding behaviours, metabolism and age-related health.The work proposed here will use the nematode worm Caenorhabditis elegans to investigate the brain-gut relationship between these two pathways. The worm is perfect for this as it comes with a ready-made genetic toolkit, including: mutants that allow us to study the function of specific genes/molecules; fluorescent reporters allowing us to see where and when molecules are switched on or off; and a fully mapped nervous system so that we know exactly which neurons signal to each other. This useful and cost-effective model will allow us to establish the molecular sequence of events from the sensing of food, to neuronal Nrf signalling, to UPR activation. In addition, these tiny animals are excellent models for eating behaviour, age-related health, and lifespan, allowing us to probe the impact of molecular change on these processes. Identifying the molecular mechanisms that connect nutrient information with effects on metabolic health and ageing would enable the development of therapies that harness these mechanisms or target their specific molecular functions in order to therapeutically manipulate ageing and health, providing avenues to delay and treat both diet-induced and other non-communicable diseases associated with age.

我们吃的东西对我们的终生健康产生了重大影响。超重会导致多种疾病，其严重程度因年龄而加剧。这使得了解饮食如何影响衰老过程，并找到操纵饮食的方法，这是研究和公共卫生政策的重要优先事项。营养是已知的寿命调节剂。通过调节食物摄入量，可以提高寿命并改善与年龄相关的健康。饮食限制或间歇性禁食，甚至通过简单地闻到养分水平的变化。该项目研究了与其他代谢组织（如肠道（称为脑肠轴））的变化相关的营养感，并将其与饮食行为，代谢健康和衰老联系起来。识别与营养 - 脑反应有关的新分子靶标提供了治疗与年龄相关的病理和改善健康的切实方法。最近，泰勒（Taylor）和塔特（Tulet）实验室独立识别并发表了两种引人注目的候选途径，这些途径将营养感与与年龄相关的健康联系起来。这些是内质网（ER）的NF-E2相关转录因子（NRF）和未折叠的蛋白质反应（UPR）。这项协作赠款汇集了我们过去的工作和新的初步数据以完成图片。我们假设NRF在神经元中起作用，以传达有关饮食的信息并调节肠道中的UPR激活。一系列事件将控制营养调节的喂养行为，代谢和与年龄相关的健康。这里提出的工作将使用线虫蠕虫秀丽隐杆线虫来研究这两种途径之间的脑脉络关系。蠕虫非常适合它，因为它带有现成的遗传工具包，包括：突变体使我们能够研究特定基因/分子的功能；荧光记者使我们能够查看分子打开或关闭分子的何时何地；以及完全映射的神经系统，以便我们确切知道哪些神经元相互信号。这种有用且具有成本效益的模型将使我们能够建立从食物传感到神经元NRF信号传导再到UPR激活的事件的分子序列。此外，这些小动物是饮食行为，与年龄相关的健康和寿命的绝佳模型，使我们能够探究分子变化对这些过程的影响。确定将养分信息与对代谢健康和衰老的影响联系起来的分子机制将使疗法的发展构成这些机制或针对其特定的分子功能，以便在治疗上操纵衰老和健康，从而延迟饮食诱导和其他与年龄相关的饮食诱导和治疗其他疾病。