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

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，在以后的生活中有更多的健康问题。我们的目标是开发基于血液的生物年龄测量方法，在实际年龄本身的基础上，提供更好的对成人健康不良和过早死亡以及儿童发育结果的预测。我们将从英国、欧洲和美国的多个人群队列研究中获得现有的代谢组学(全套小分子)和其他“组学”数据(与基因控制和功能相关的全套分子)。我们将利用先进的统计方法，发展由多个分子测量组成的生物年龄血液检测。将采用三种方法：i)在大约35,000人(年龄7-99岁)中对200多个分子使用定向代谢组学；ii)在大约7,000人(年龄20-95岁)中对数千个分子使用非定向代谢组学。将确定预测代谢物，新的血液测试将使用新测量的数据在一个独立的人群中进行测试；iii)使用1,200名儿童(6-11岁)的代谢和组学数据来开发生物发育的血液测试。然后，我们将评估年龄加速，即预测年龄(通过代谢和基因组血液测试)与实际年龄之间的差异，是否可以预测成人的心血管疾病和过早死亡，并与儿童的身高、体重和智力发育相关。我们将确定导致老龄化加速的主要环境和遗传原因，以及导致老龄化过程的生物学途径。

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.