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

遗传和环境因素都会影响衰老过程，导致衰老速度的差异。因此，一个人的“生理年龄”，或整体生理状态，可能与他们实际（实足）年龄的预期不同。生物衰老率的差异意味着一些人死得早，晚年有更多的健康问题。我们的目标是开发基于血液的生物年龄测量方法，以更好地预测成人的健康状况不佳和过早死亡，以及儿童的发育结果。我们将从英国、欧洲和美国的多个基于人群的队列研究中获得现有的代谢组学（整套小分子）和其他“组学”（与基因控制和功能相关的整套分子）数据。我们将利用先进的统计技术开发由多种分子测量组成的生物年龄血液测试。将采用三种方法：i)对大约35,000人（7-99岁）的200多个分子使用靶向代谢组学；ii)对大约7000人（年龄在20-95岁之间）的数千个分子使用非靶向代谢组学。预测代谢物将被确定，新的血液测试将在独立人群中使用新测量的数据进行测试；（三）利用1 200名儿童（6-11岁）的代谢组学和组学数据开展生物发育血液检测。然后，我们将评估“年龄加速”，即预测年龄（来自代谢组学和组学年龄血液测试）与实际年龄之间的差异，是否可以预测成人心血管疾病和过早死亡，并与儿童的身高、体重和智力发育有关。我们将确定年龄加速的关键环境和遗传原因以及衰老过程背后的生物途径。

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.We aim to develop blood-based measures of biological age that provides improved prediction, over chronological age itself, of ill health and premature mortality in adults and developmental outcomes in children.We will existing metabolomics (whole sets of small molecules) and other 'omics' (whole sets of molecules related to gene control and function) data from multiple population based cohort studies in the UK, Europe and the USA. We will develop blood tests of biological age composed of measurements of multiple molecules using advanced statistics. Three approaches will be pursued:i) Using targeted metabolomics on over 200 molecules in approximately 35,000 people (aged 7-99 years);ii) Using untargeted metabolomics on several thousand molecules in approximately 7,000 people (aged 20-95 years). Predictive metabolites will be identified, and the new blood test will tested with newly measured data in an independent population;iii) Using metabolomic and omics data in 1,200 children (aged 6-11 years) to develop blood tests of biological development.We will then assess whether 'age acceleration', the difference between predicted age (from metabolomic and omic age blood tests) and chronological age, is predictive of cardiovascular disease and premature death in adults and associated with height, weight, and mental development in children. We will identify the key environmental and genetic causes of age acceleration and the biological pathways underlying the ageing process.