Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging

Erik B van den Akker, Willemijn M Passtoors, Rick Jansen, Erik W van Zwet, Jelle J Goeman, Marc Hulsman, Valur Emilsson, Markus Perola, Gonneke Willemsen, Brenda W J H Penninx, Bas T Heijmans, Andrea B Maier, Dorret I Boomsma, Joost N Kok, Pieternella E Slagboom, Marcel J T Reinders, Marian Beekman

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein-protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10(-38)) enriched for 'T-cell activation' marking age-associated shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 × 10(-10)). Adjusting the analysis in the compendium for the 'T-cell activation' module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for 'Translational elongation', 'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.

Original languageEnglish
Pages (from-to)216-25
Number of pages10
JournalAging Cell
Volume13
Issue number2
DOIs
Publication statusPublished - Apr 2014

Fingerprint

Meta-Analysis
Proteins
T-Lymphocytes
Blood Cell Count
Life Expectancy
Databases
Lymphocytes
Survival
DNA
Health
Genes

Bibliographical note

© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Keywords

  • Aged, 80 and over
  • Aging/blood
  • Biomarkers/blood
  • Cell Cycle Proteins/genetics
  • Databases, Genetic
  • Gene Expression Regulation
  • Humans
  • Lymphocyte Activation/genetics
  • Lymphocyte Count
  • Protein Interaction Maps/genetics
  • Reproducibility of Results
  • Survival Analysis
  • T-Lymphocytes/immunology
  • Transcriptome/genetics

Cite this

van den Akker, E. B., Passtoors, W. M., Jansen, R., van Zwet, E. W., Goeman, J. J., Hulsman, M., ... Beekman, M. (2014). Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging. Aging Cell, 13(2), 216-25. https://doi.org/10.1111/acel.12160
van den Akker, Erik B ; Passtoors, Willemijn M ; Jansen, Rick ; van Zwet, Erik W ; Goeman, Jelle J ; Hulsman, Marc ; Emilsson, Valur ; Perola, Markus ; Willemsen, Gonneke ; Penninx, Brenda W J H ; Heijmans, Bas T ; Maier, Andrea B ; Boomsma, Dorret I ; Kok, Joost N ; Slagboom, Pieternella E ; Reinders, Marcel J T ; Beekman, Marian. / Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging. In: Aging Cell. 2014 ; Vol. 13, No. 2. pp. 216-25.
@article{b1e8163da7114f2999bd582eb5cb349c,
title = "Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging",
abstract = "The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein-protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10(-38)) enriched for 'T-cell activation' marking age-associated shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 × 10(-10)). Adjusting the analysis in the compendium for the 'T-cell activation' module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for 'Translational elongation', 'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.",
keywords = "Aged, 80 and over, Aging/blood, Biomarkers/blood, Cell Cycle Proteins/genetics, Databases, Genetic, Gene Expression Regulation, Humans, Lymphocyte Activation/genetics, Lymphocyte Count, Protein Interaction Maps/genetics, Reproducibility of Results, Survival Analysis, T-Lymphocytes/immunology, Transcriptome/genetics",
author = "{van den Akker}, {Erik B} and Passtoors, {Willemijn M} and Rick Jansen and {van Zwet}, {Erik W} and Goeman, {Jelle J} and Marc Hulsman and Valur Emilsson and Markus Perola and Gonneke Willemsen and Penninx, {Brenda W J H} and Heijmans, {Bas T} and Maier, {Andrea B} and Boomsma, {Dorret I} and Kok, {Joost N} and Slagboom, {Pieternella E} and Reinders, {Marcel J T} and Marian Beekman",
note = "{\circledC} 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.",
year = "2014",
month = "4",
doi = "10.1111/acel.12160",
language = "English",
volume = "13",
pages = "216--25",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "2",

}

van den Akker, EB, Passtoors, WM, Jansen, R, van Zwet, EW, Goeman, JJ, Hulsman, M, Emilsson, V, Perola, M, Willemsen, G, Penninx, BWJH, Heijmans, BT, Maier, AB, Boomsma, DI, Kok, JN, Slagboom, PE, Reinders, MJT & Beekman, M 2014, 'Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging' Aging Cell, vol. 13, no. 2, pp. 216-25. https://doi.org/10.1111/acel.12160

Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging. / van den Akker, Erik B; Passtoors, Willemijn M; Jansen, Rick; van Zwet, Erik W; Goeman, Jelle J; Hulsman, Marc; Emilsson, Valur; Perola, Markus; Willemsen, Gonneke; Penninx, Brenda W J H; Heijmans, Bas T; Maier, Andrea B; Boomsma, Dorret I; Kok, Joost N; Slagboom, Pieternella E; Reinders, Marcel J T; Beekman, Marian.

In: Aging Cell, Vol. 13, No. 2, 04.2014, p. 216-25.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Meta-analysis on blood transcriptomic studies identifies consistently coexpressed protein-protein interaction modules as robust markers of human aging

AU - van den Akker, Erik B

AU - Passtoors, Willemijn M

AU - Jansen, Rick

AU - van Zwet, Erik W

AU - Goeman, Jelle J

AU - Hulsman, Marc

AU - Emilsson, Valur

AU - Perola, Markus

AU - Willemsen, Gonneke

AU - Penninx, Brenda W J H

AU - Heijmans, Bas T

AU - Maier, Andrea B

AU - Boomsma, Dorret I

AU - Kok, Joost N

AU - Slagboom, Pieternella E

AU - Reinders, Marcel J T

AU - Beekman, Marian

N1 - © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PY - 2014/4

Y1 - 2014/4

N2 - The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein-protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10(-38)) enriched for 'T-cell activation' marking age-associated shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 × 10(-10)). Adjusting the analysis in the compendium for the 'T-cell activation' module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for 'Translational elongation', 'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.

AB - The bodily decline that occurs with advancing age strongly impacts on the prospects for future health and life expectancy. Despite the profound role of age in disease etiology, knowledge about the molecular mechanisms driving the process of aging in humans is limited. Here, we used an integrative network-based approach for combining multiple large-scale expression studies in blood (2539 individuals) with protein-protein Interaction (PPI) data for the detection of consistently coexpressed PPI modules that may reflect key processes that change throughout the course of normative aging. Module detection followed by a meta-analysis on chronological age identified fifteen consistently coexpressed PPI modules associated with chronological age, including a highly significant module (P = 3.5 × 10(-38)) enriched for 'T-cell activation' marking age-associated shifts in lymphocyte blood cell counts (R(2) = 0.603; P = 1.9 × 10(-10)). Adjusting the analysis in the compendium for the 'T-cell activation' module showed five consistently coexpressed PPI modules that robustly associated with chronological age and included modules enriched for 'Translational elongation', 'Cytolysis' and 'DNA metabolic process'. In an independent study of 3535 individuals, four of five modules consistently associated with chronological age, underpinning the robustness of the approach. We found three of five modules to be significantly enriched with aging-related genes, as defined by the GenAge database, and association with prospective survival at high ages for one of the modules including ASF1A. The hereby-detected age-associated and consistently coexpressed PPI modules therefore may provide a molecular basis for future research into mechanisms underlying human aging.

KW - Aged, 80 and over

KW - Aging/blood

KW - Biomarkers/blood

KW - Cell Cycle Proteins/genetics

KW - Databases, Genetic

KW - Gene Expression Regulation

KW - Humans

KW - Lymphocyte Activation/genetics

KW - Lymphocyte Count

KW - Protein Interaction Maps/genetics

KW - Reproducibility of Results

KW - Survival Analysis

KW - T-Lymphocytes/immunology

KW - Transcriptome/genetics

U2 - 10.1111/acel.12160

DO - 10.1111/acel.12160

M3 - Article

VL - 13

SP - 216

EP - 225

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 2

ER -