Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs

Aging Cell

Martijs J. Jonker³  Joost P. M. Melis¹  Raoul V. Kuiper¹  Tessa V. van der Hoeven³  Paul F. K. Wackers³  Joke Robinson¹  Gijsbertus T. J. van der Horst²  Martijn E. T. Dollé¹  Jan Vijg⁴  Timo M. Breit³  Jan H. J. Hoeijmakers² 

[1] National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, The Netherlands;CGC Department of Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands;MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), University of Amsterdam (UvA), Amsterdam, The Netherlands;Department of Genetics, Albert Einstein College of Medicine, New York, NY, USA

关键词: aging dynamics;    database;    gene expression;    in vivo;    pathology;   

DOI  :  10.1111/acel.12118

来源: Wiley

【 摘 要 】

Summary

Aging and age-related pathology is a result of a still incompletely understood intricate web of molecular and cellular processes. We present a C57BL/6J female mice in vivo aging study of five organs (liver, kidney, spleen, lung, and brain), in which we compare genome-wide gene expression profiles during chronological aging with pathological changes throughout the entire murine life span (13, 26, 52, 78, 104, and 130 weeks). Relating gene expression changes to chronological aging revealed many differentially expressed genes (DEGs), and altered gene sets (AGSs) were found in most organs, indicative of intraorgan generic aging processes. However, only ≤ 1% of these DEGs are found in all organs. For each organ, at least one of 18 tested pathological parameters showed a good age-predictive value, albeit with much inter- and intraindividual (organ) variation. Relating gene expression changes to pathology-related aging revealed correlated genes and gene sets, which made it possible to characterize the difference between biological and chronological aging. In liver, kidney, and brain, a limited number of overlapping pathology-related AGSs were found. Immune responses appeared to be common, yet the changes were specific in most organs. Furthermore, changes were observed in energy homeostasis, reactive oxygen species, cell cycle, cell motility, and DNA damage. Comparison of chronological and pathology-related AGSs revealed substantial overlap and interesting differences. For example, the presence of immune processes in liver pathology-related AGSs that were not detected in chronological aging. The many cellular processes that are only found employing aging-related pathology could provide important new insights into the progress of aging.

【 授权许可】

Unknown   
© 2013 The Anatomical Society and John Wiley & Sons Ltd