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.

遗传因素和环境因素都会影响衰老过程，导致老龄化速度的差异。因此，一个人的“生物学年龄”，或整体的生理状态，可能与他们实际(按时间顺序)的年龄所期望的有所不同。生物衰老速度的差异意味着一些人死得更早，在晚年会有更多的健康问题。在我的项目的第一部分，我使用了代谢组学(全套代谢物或小分子)数据，这些数据来自英国、欧洲和美国的多个基于人群的队列研究，利用先进的统计数据来开发生物年龄的血液测试。我们发现，基于代谢组学的生物年龄测试提供了比实际年龄本身更好的年龄相关疾病和死亡率的预测。此外，我们发现，在Finger研究中，与没有接受这种支持的人相比，得到支持以遵循更健康的生活方式的人在两年内的生物衰老速度较慢。在我的项目的下一部分，我将在两项针对老年人的队列研究(Chariot Pro和Tilda研究)中，检查基于新陈代谢的生物年龄测试是否可以预测认知和身体衰老。我将进一步改进基于代谢组学的生物年龄测试，这样它就更便宜，更容易在临床实验室中进行测量。我还将测试蛋白质的使用，这是另一类具有生物重要性的分子，在EPIC和CHAROTT PRO研究中，以2万多人为对象建立生物年龄模型。因为我们知道体内哪些器官产生特定的蛋白质，所以就有可能测试“特定器官”的衰老。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的疾病的器官特定衰老。此外，我将使用遗传数据和一种名为Medelian Randomization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。我将利用这些信息来进一步改进生物年龄测试。最后，我将分析与衰老有关的蛋白质、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。