Blood RNA expression profiles undergo major changes during the seventh decade

// Marius Gheorghe 1 , Claudia Schurmann 3, 6 Marjolein J. Peters 2 , Andre G. Uitterlinden 2, 5 , Albert Hofman 2, 5 , Reiner Biffar 7 , Georg Homuth 3 , Uwe Volker 3 , Joyce BJ van Meurs 2 , Vered Raz 4 1 Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands 2 Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands 3 Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475 DE, Germany 4 Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, 2300 RC, The Netherlands 5 Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands 6 The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America 7 Department of Prosthodontics, Gerodontology and Biomaterials, University Medicine Greifswald, Greifswald, 17475 DE, Germany Correspondence to: Vered Raz, email: v.raz@lumc.nl Keywords: blood aging, population based studies, RNA expression profiles, sample weighting, b-spline regression model Received: June 06, 2016      Accepted: September 05, 2016      Published: September 17, 2016 ABSTRACT Genome-wide alterations in RNA expression profiles are age-associated. Yet the rate and temporal pattern of those alterations are poorly understood. We investigated temporal changes in RNA expression profiles in blood from population-based studies using a quadratic regression model. Comparative analysis between two independent studies was carried out after sample-weighting that downsized differences in sample distribution over age between the datasets. We show that age-associated expression profiles are clustered into two major inclinations and transcriptional alternations occur predominantly from the seventh decade onwards. The age-associated genes in blood are enriched in functional groups of the translational machinery and the immune system. The results are highly consistent between the two population-based studies indicating that our analysis overcomes potential confounders in population-based studies. We suggest that the critical age when major transcriptional alterations occur could help understanding aging and disease risk during adulthood.