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

Autor: Jonker MJ; University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.; Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands., Melis JP; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.; Leiden University Medical Center, Department of Toxicogenetics, Leiden, the Netherlands., Kuiper RV; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.; Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of veterinary medicine, Utrecht University, Utrecht, The Netherlands., van der Hoeven TV; University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands., Wackers PFK; University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.; Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands.; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands., Robinson J; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.; Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of veterinary medicine, Utrecht University, Utrecht, The Netherlands., van der Horst GT; Erasmus University Medical Center, CGC Department of Genetics, Rotterdam, The Netherlands., Dollé ME; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands., Vijg J; Albert Einstein College of Medicine, Department of Genetics, New York, USA., Breit TM; University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.; Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands., Hoeijmakers JH; Erasmus University Medical Center, CGC Department of Genetics, Rotterdam, The Netherlands., van Steeg H; National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.; Leiden University Medical Center, Department of Toxicogenetics, Leiden, the Netherlands.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2013 Oct; Vol. 12 (5), pp. 901-909. Date of Electronic Publication: 2013 Jul 14.
DOI: 10.1111/acel.12118
Abstrakt: 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.
(© 2013 The Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: