Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, 80309, USA.
Department of Mathematics, University of Colorado Boulder, Boulder, CO, 80309, USA.
Geroscience. 2019 Dec;41(6):895-906. doi: 10.1007/s11357-019-00123-w. Epub 2019 Nov 9.
Chronological age is an important predictor of morbidity and mortality; however, it is unable to account for heterogeneity in the decline of physiological function and health with advancing age. Several attempts have been made to instead define a "biological age" using multiple physiological parameters in order to account for variation in the trajectory of human aging; however, these methods require technical expertise and are likely too time-intensive and costly to be implemented into clinical practice. Accordingly, we sought to develop a metabolomic signature of biological aging that could predict changes in physiological function with the convenience of a blood sample. A weighted model of biological age was generated based on multiple clinical and physiological measures in a cohort of healthy adults and was then applied to a group of healthy older adults who were tracked longitudinally over a 5-10-year timeframe. Plasma metabolomic signatures were identified that were associated with biological age, including some that could predict whether individuals would age at a faster or slower rate. Metabolites most associated with the rate of biological aging included amino acid, fatty acid, acylcarnitine, sphingolipid, and nucleotide metabolites. These results not only have clinical implications by providing a simple blood-based assay of biological aging, but also provide insight into the molecular mechanisms underlying human healthspan.
年龄是发病率和死亡率的重要预测因素；然而，它无法解释随着年龄的增长生理功能和健康下降的异质性。已经有几种尝试使用多个生理参数来定义“生物年龄”，以解释人类衰老轨迹的变化；然而，这些方法需要技术专业知识，并且可能过于耗时和昂贵，无法在临床实践中实施。因此，我们试图开发一种代谢组学特征的生物年龄，可以通过血液样本的便利性来预测生理功能的变化。在一组健康成年人中，基于多个临床和生理指标生成了生物年龄的加权模型，然后将其应用于一组在 5-10 年时间框架内进行纵向跟踪的健康老年人。确定了与生物年龄相关的血浆代谢组学特征，包括一些可以预测个体衰老速度更快或更慢的特征。与生物衰老速度最相关的代谢物包括氨基酸、脂肪酸、酰基辅酶 A、神经鞘脂和核苷酸代谢物。这些结果不仅通过提供一种简单的基于血液的生物年龄测定法具有临床意义，而且还提供了对人类健康跨度的分子机制的深入了解。
