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“生物年龄”或整体生理状态可能与他们的实际（时间）年龄所预期的不同。生物衰老率的差异意味着有些人会死得更早，在晚年会有更多的健康问题。我们的目标是开发基于血液的生物年龄测量方法，提供更好的预测，超过实际年龄本身，健康状况不佳和过早死亡的成年人和儿童的发育结果。我们将现有的代谢组学（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）数据来自英国、欧洲和美国的多个基于人群的队列研究。我们将开发生物年龄的血液测试，包括使用先进的统计学测量多个分子。将采用三种方法：i）在约35，000人（7-99岁）中使用靶向代谢组学研究200多个分子;ii）在约7，000人（20-95岁）中使用非靶向代谢组学研究数千个分子。将确定预测代谢物，并在独立人群中使用新测量的数据对新的血液检测进行测试; ㈢利用1 200名儿童的代谢组学和组学数据（6-11岁）制定血液生物发育测试。然后，我们将评估是否'年龄加速'，预测年龄之间的差异（来自代谢组学和组学年龄血液测试）和实足年龄，是成人心血管疾病和过早死亡的预测因子，并且与儿童的身高、体重和智力发育相关。我们将确定衰老加速的主要环境和遗传原因以及衰老过程的生物学途径。

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.