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，导致衰老速度存在差异。因此，一个人的“生物年龄”或整体生理状态可能与其实际（按时间顺序）年龄的预期不同。生物衰老率的差异意味着有些人会更早死亡，并且在晚年会出现更多的健康问题。在我的项目的第一部分中，我使用来自英国、欧洲和美国多个基于人群的队列研究的代谢组学（整组代谢物或小分子）数据，利用先进的统计数据开发生物年龄的血液测试。我们发现，与实际年龄本身相比，基于代谢组学的生物年龄测试可以更好地预测与年龄相关的健康状况不佳和死亡率。此外，我们发现，在 FINGER 研究中，与未接受更健康生活方式支持的人相比，在两年内获得支持的人的生物衰老速度较慢。在我的项目的下一部分中，我将研究基于代谢组学的生物年龄测试是否可以在两项针对老年人的队列研究（CHARIOT PRO 和 TILDA 研究）中预测认知和身体衰老。我将进一步完善基于代谢组学的生物年龄测试，使其更便宜且更容易在临床实验室中测量。我还将在 EPIC 和 CHIOT PRO 研究中测试使用蛋白质（另一类生物学上重要的分子）来为 20,000 多人开发生物年龄模型。由于我们知道体内的哪些器官产生特定蛋白质，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以不同的速度老化，我将针对多种类型的疾病测试器官特异性老化。此外，我将使用遗传数据和一种称为麦德尔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。我将利用这些信息进一步改进生物年龄测试。最后，我将分析与衰老相关的蛋白质、代谢物和遗传因素之间的联系途径，以更深入地了解随年龄变化的生物过程。