Metabolomic and omic assessment of biological ageing across the life-course (METAGE)

生命全程生物衰老的代谢组学和组学评估 (METAGE)

• 批准号: MR/Y02012X/1
• 负责人: Oliver Robinson
• 金额: $ 75.69万
• 依托单位: Imperial College London
• 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%2FY02012X%2F1
• 关键词: Metabolomic; omic; assessment; biological; ageing

Both genetic and environmental factors affect the ageing process, leading to differences in ageing rates. Therefore, a person's "biological age", or overall physiological state, may differ from what is expected given their actual (chronological) age. Differences in biological aging rates mean some people die earlier and have more health problems in later life. In the first part of my project, I used metabolomics (whole sets of metabolites or small molecules) data from multiple population-based cohort studies in the UK, Europe, and the USA, to develop blood tests of biological age using advanced statistics. We found that the metabolomic-based biological age tests provided improved prediction, over chronological age itself, of age-related ill health and mortality. Furthermore, We found that that biological ageing was slower over two years among people who were supported to follow a healthier lifestyle, compared to those who did not receive this support in the FINGER study. For the next part of my project, I will examine if the metabolomic-based biological age test can predict cognitive and physical aging among two cohort studies of older people (the CHARIOT PRO and TILDA studies). I will further refine the metabolomic-based biological age test, so it is less expensive and easier to measure in clinical laboratories. I will also test the use of proteins, another biologically important class of molecules, to develop biological age models in over 20,000 people in the EPIC and CHARIOT PRO studies. Since we know which organs in the body produce specific proteins, it is possible to test "organ-specific" ageing. This is useful as different biological systems in the body may age at different rates, and I will test organ-specific ageing against many types of disease. Furthermore, I will use genetic data and a technique called Medelian Randomization to test if proteins and metabolites that are correlated with age, may cause unhealthy ageing. I will use this information to further improve the biological age tests. Finally, I will analysis the pathways that connect proteins, metabolites and genetic factors involved in ageing to more deeply understand the biological processes that change with age.

遗传和环境因素都会影响衰老过程，从而导致衰老率差异。因此，一个人的“生物年龄”或整体生理状态可能与预期的（按年代）年龄有所不同。生物衰老率的差异意味着有些人早就死亡，并且在以后的生活中有更多的健康问题。在项目的第一部分中，我使用了来自英国，欧洲和美国的多个基于人群的队列研究的代谢组学（整个代谢产物或小分子）数据，用于使用高级统计数据来开发生物年龄的血液测试。我们发现，基于代谢组的生物年龄测试为年龄与年龄相关的健康和死亡率提供了改进的预测。此外，我们发现，与未在手指研究中没有得到这种支持的人相比，受支持遵循更健康生活方式的人中的生物衰老较慢。对于我项目的下一部分，我将检查基于代谢组的生物年龄测试是否可以预测两种老年人的队列研究中的认知和身体衰老（Chariot Pro和Tilda研究）。我将进一步完善基于代谢组的生物年龄测试，因此在临床实验室中较便宜且易于测量。我还将测试蛋白质的使用，蛋白质是另一个重要的生物学分子类别，以在史诗和战车研究中开发20,000多人的生物年龄模型。由于我们知道体内哪种器官会产生特定的蛋白质，因此可以测试“器官特异性”衰老。这很有用，因为体内不同的生物系统可能会以不同的速度衰老，我将测试针对许多类型疾病的器官特异性衰老。此外，我将使用遗传数据和一种称为中间随机化的技术来测试与年龄相关的蛋白质和代谢物是否可能导致不健康的衰老。我将使用此信息进一步改善生物年龄测试。最后，我将分析与衰老有关的蛋白质，代谢产物和遗传因素联系起来的途径，以更深入地了解随着年龄的变化而变化的生物学过程。