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COMPARISON OF BIOLOGICAL AGE ESTIMATES IN HEALTHY INDIVIDUALS: TOWARD PLASMA-BASED QUANTIFICATION

F. de Wolf, E. Brinkman, G. Weverling, P. Klatser,S. Kostense, F. Schmitz,W. Koudstaal,J. Goudsmit

Innovation in aging(2017)

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摘要
Biological Age (BA) assesses a person’s deviation from chronological age and is an estimate of the individual’s health status. Through quantification of multiple biomarkers one can predict the individual’s aging process and mortality risk better than by chronological age alone. Several methods have been developed to compute a person’s BA (1–4). Here we compare an BA estimate relying on biochemical and functional parameters (measured in different matrixes)- referred to as ClinicalAge (1) and three BA estimates based on methylation levels of specific DNA CpG sites obtained from PBMCs- termed DNAmAge (2–4) from the same cohort. All measurements were obtained from 60 healthy individuals subdivided in a young (mean 23.9; range 20–30 yrs), middle (45.8; 40–50) and older (65.3; 60–70) age group. Correlations among ClinicalAge and DNAmAge were low, whereas the three DNAmAge estimates strongly correlated with each other. Validation of any BA estimate with respect to its predictive power for mortality and ultimately all-cause morbidity requires large diverse cohort studies with longitudinal follow-up. Previously described BA surrogates were determined by various biomarkers quantified in distinct matrixes of body fluids, which are not all available on large scale in cohort studies. Therefore we aim to investigate the feasibility to measure BA in plasma only. Here we demonstrate that a unique set of epigenetic markers can be quantified in plasma and strongly correlated with chronological age. Ultimately, we established strategies to develop a BA estimate using plasma biomarkers, which subsequently needs to be derived and validated in longitudinal cohort studies. 1. D. W. Belsky et al., PNAS (2015) 2. G. Hannum et al., Molecular cell 49, 359 (2013) 3. S. Horvath et al., Genome Biol 14, R115 (2013) 4. C. I. Weidner et al., Genome Biol 15, R24 (2014)
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