The role of dietary and blood proteins in the prevention and development of major age-related diseases

膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用

• 批准号: MR/X032809/1
• 负责人: Tammy Tong
• 金额: $ 120.08万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=MR%2FX032809%2F1
• 关键词: role; dietary; blood; proteins; prevention

The United Kingdom's (UK) population is ageing. As a result, common age-related diseases, such as stroke, fractures and dementia, are predicted to pose an increasing burden on the health system. The development of prevention strategies is therefore an imperative. Emerging evidence has suggested mechanistic links between these age-related diseases. For example, higher risks of hip fractures and dementia have been observed in people who have had a stroke, while a higher risk of hip fractures has also been observed in people who have dementia. These associations may be partly due to the first condition altering the risk of the second condition, but recent evidence suggests that the three conditions might share common risk factors including diet. Of the potentially modifiable risk factors, differences in the amount and quality of dietary protein intake have been suggested to be important. Specifically, low intakes of high quality protein have been associated with higher risks of haemorrhagic stroke (the more aggressive stroke type) and of hip fractures, possibly because protein is a key structural component for maintaining the strength and integrity of blood vessels and bones. The possible relevance of dietary protein intake in the risk for dementia development has been less studied, but low blood levels of insulin-like growth factor I (IGF-I), a peptide hormone that is known to be influenced by dietary protein intake, have been suggested to increase the risk of dementia as well as stroke and fractures. Research is needed to understand the effects of dietary protein adequacy and quality on common age-related diseases. This is particularly relevant in light of the global calls to limit animal source food consumption due to their high environmental impact, though these foods are generally considered higher quality proteins. Understanding the exact role of protein adequacy and quality will guide strategies to ensure optimal protein intakes, without compromising sustainability targets. This research will examine the role of dietary protein intake, focusing on quality as well as quantity, and protein-related biomarkers in the development of stroke subtypes, hip fractures, vascular dementia and Alzheimer's disease, and seek to clarify the links between the three sets of conditions, using data from large prospective cohorts in the UK and in other countries. The first work package will examine how differences in intakes of dietary protein, protein from different sources and protein rich foods affect the risk of each of the conditions of interest. I will also investigate the role of individual dietary amino acids, which make up dietary proteins, with the aim of investigating the association between protein quality and health. The second work package will explore how differences in protein intake influence the levels of protein-related biomarkers in the body, and how these biomarkers may be associated with disease risk, as a way of identifying potential disease mechanisms. This will include the examination of established clinical biomarkers (e.g. IGF-I), circulating amino acids and approximately 1500 novel circulating proteins (proteomics). It will also involve the use of genetic instruments to establish the causal relevance of the biomarkers of interest for disease risk. The third work package will investigate the mechanistic links between the three sets of diseases and the sequence of multimorbidity. I will identify the common dietary and non-dietary risk factors for the three outcomes, and evaluate whether the manifestation of the first condition has a direct effect on the development of multimorbidity, independent of the common risk factors. Overall, this programme of work will generate robust evidence on modifiable risk factors for common age-related diseases and the potential underlying mechanisms, and inform the optimal targets for strategies in disease prevention.

英国的人口正在老龄化。因此，中风、骨折和痴呆等常见的与年龄有关的疾病预计将给卫生系统带来越来越大的负担。因此，必须制定预防战略。新出现的证据表明，这些与年龄有关的疾病之间存在机械联系。例如，在中风患者中观察到髋部骨折和痴呆症的风险较高，而在痴呆症患者中也观察到髋部骨折的风险较高。这些关联可能部分是由于第一种情况改变了第二种情况的风险，但最近的证据表明，这三种情况可能有共同的风险因素，包括饮食。在潜在的可改变的风险因素中，膳食蛋白质摄入量和质量的差异被认为是重要的。具体而言，高质量蛋白质的低摄入量与出血性中风（更具侵袭性的中风类型）和髋部骨折的风险较高有关，可能是因为蛋白质是维持血管和骨骼强度和完整性的关键结构成分。膳食蛋白质摄入量与痴呆症发展风险的可能相关性研究较少，但胰岛素样生长因子I（IGF-I）的低血液水平，已知受膳食蛋白质摄入量影响的肽激素，已被认为会增加痴呆症以及中风和骨折的风险。需要进行研究，以了解膳食蛋白质充足性和质量对常见年龄相关疾病的影响。鉴于全球呼吁限制动物源食品消费，这一点尤其重要，因为它们对环境的影响很大，尽管这些食品通常被认为是高质量的蛋白质。了解蛋白质充足性和质量的确切作用将指导战略，以确保最佳蛋白质摄入量，而不影响可持续性目标。这项研究将研究膳食蛋白质摄入量的作用，重点是质量和数量，以及中风亚型，髋部骨折，血管性痴呆和阿尔茨海默病发展中的蛋白质相关生物标志物，并试图澄清三组条件之间的联系，使用来自英国和其他国家的大型前瞻性队列的数据。第一个工作包将研究膳食蛋白质、不同来源的蛋白质和富含蛋白质的食物的摄入量差异如何影响每种感兴趣的疾病的风险。我还将研究构成膳食蛋白质的单个膳食氨基酸的作用，目的是研究蛋白质质量与健康之间的关系。第二个工作包将探索蛋白质摄入量的差异如何影响体内蛋白质相关生物标志物的水平，以及这些生物标志物如何与疾病风险相关，作为识别潜在疾病机制的一种方式。这将包括对已建立的临床生物标志物（例如IGF-I）、循环氨基酸和大约1500种新型循环蛋白质（蛋白质组学）的检查。它还将涉及使用遗传工具来确定感兴趣的生物标志物与疾病风险的因果关系。第三个工作包将调查这三组疾病与多发病顺序之间的机械联系。我将确定三种结果的常见饮食和非饮食风险因素，并评估第一种情况的表现是否对多发性硬化症的发展有直接影响，独立于常见的风险因素。总的来说，这一工作方案将产生关于常见年龄相关疾病可改变的风险因素和潜在的基本机制的有力证据，并为疾病预防战略的最佳目标提供信息。