Plasma metabolome as a predictor of biological aging

Abstract

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, a metabolomic signature of biological aging was developed that can 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 large group of healthy adults and was then applied to a cohort 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. 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.