Measuring Biological Age via Metabonomics: The Metabolic Age Score

Abstract

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity. Applying a nonlinear regression technique, we constructed a metabonomic measurement for biological age, the metabolic age score, based on urine data measured via (1)H NMR spectroscopy. We validated the score in two large independent population-based samples by revealing its significant associations with chronological age and age-related clinical phenotypes as well as its independent predictive value for survival over approximately 13 years of follow-up. Furthermore, the metabolic age score was prognostic for weight loss in a sample of individuals who underwent bariatric surgery. We conclude that the metabolic age score is an informative measurement of biological age with possible applications in personalized medicine.

Biological Age Predictors

“…Relatively few studies have analyzed associations with age on the metabolome (also referred to as the metabonome), and they were conducted using different measurement techniques (Ishikawa et al, 2014, Yu et al, 2012, Menni et al, 2013, Hertel et al, 2016, Collino et al, 2013, Lawton et al, 2008). Yu and colleagues used a targeted mass-spectrometry method identifying 131 metabolites in fasting serum, where 11 were independently associated with age in females, both in discovery (KORA F4) and replication (TwinsUK), after BMI adjustments (Yu et al, 2012).…”

“…In a study from 2016 by Hertel and colleagues, a proton nuclear magnetic resonance (H 1 NMR) spectroscopy investigation in human urine samples quantified 59 metabolites (Hertel et al, 2016). Construction of a Metabolic Age Score included all metabolites as predictors and age as the outcome.…”

“…2Number of studies versus mortality hazards for the biological age predictors. Overview of the four biological age predictors telomere length (Rode et al, 2015), epigenetic clock (Chen et al, 2016), Metabolic Age Score (Hertel et al, 2016), and composite biomarker (Levine, 2013) which have all been used in survival models. The hazard ratio per yearly change in biological age (de-)acceleration for each predictor is presented on the x-axis.…”

Shifting the focus of aging research into earlier decades of life

“…One possibility is that the biological processes that determine differential rates of telomere shortening had already taken place in the subjects studied. The question of how best to precisely quantify biological aging is a focus of intensive research (Beach et al, 2015;Hertel et al, 2015). Future studies will develop therapeutic approaches aimed at decelerated loss of physiologic integrity earlier in the life course and extending healthy life span.…”

Role of circulating factors in cardiac aging

“…The aging process is responsible itself for several structural and functional changes and for the increased incidence of several cardiovascular risk factors such as hypertension, dyslipidemia and diabetes (2,3). The concepts that circulating factors may regulate the aging process have shed the light on this issue contributing to the development of novel therapeutic strategies to promote healthy aging (4)(5)(6).…”