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Plasma proteomic signature of age in healthy humans
Authors:Toshiko Tanaka  Angelique Biancotto  Ruin Moaddel  Ann Zenobia Moore  Marta Gonzalez‐Freire  Miguel A. Aon  Julián Candia  Pingbo Zhang  Foo Cheung  Giovanna Fantoni  Richard D. Semba  Luigi Ferrucci
Affiliation:1. Longitudinal Study Section, Translational Gerontology Branch, NIA, NIH, Baltimore, Maryland;2. Trans‐NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, Maryland;3. Laboratory of Clinical Investigation, NIA, NIH, Baltimore, Maryland;4. Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland;5. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
Abstract:To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22–93 years old, who were disease‐ and treatment‐free and had no physical and cognitive impairment. Using a p ≤ 3.83 × 10?5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10?56). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age‐associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.
Keywords:aging  aptamers  healthy aging  humans  plasma  proteomics
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