Comparative Meta-Analysis of Transcriptomics Data during Cellular Senescence and<i>In Vivo</i>Tissue Ageing

Oxidative Medicine and Cellular Longevity - Tập 2015 - Trang 1-17 - 2015
Konstantinos Voutetakis1, Aristotelis Chatziioannou1, Efstathios S. Gonos1, Ioannis P. Trougakos2
1National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece
2Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, 15784 Athens, Greece

Tóm tắt

Several studies have employed DNA microarrays to identify gene expression signatures that mark human ageing; yet the features underlying this complicated phenomenon remain elusive. We thus conducted a bioinformatics meta-analysis on transcriptomics data from human cell- and biopsy-based microarrays experiments studying cellular senescence orin vivotissue ageing, respectively. We report that coregulated genes in the postmitotic muscle and nervous tissues are classified into pathways involved in cancer, focal adhesion, actin cytoskeleton, MAPK signalling, and metabolism regulation. Genes that are differentially regulated during cellular senescence refer to pathways involved in neurodegeneration, focal adhesion, actin cytoskeleton, proteasome, cell cycle, DNA replication, and oxidative phosphorylation. Finally, we revealed genes and pathways (referring to cancer, Huntington’s disease, MAPK signalling, focal adhesion, actin cytoskeleton, oxidative phosphorylation, and metabolic signalling) that are coregulated during cellular senescence andin vivotissue ageing. The molecular commonalities between cellular senescence and tissue ageing are also highlighted by the fact that pathways that were overrepresented exclusively in the biopsy- or cell-based datasets are modules either of the same reference pathway (e.g., metabolism) or of closely interrelated pathways (e.g., thyroid cancer and melanoma). Our reported meta-analysis has revealed novel age-related genes, setting thus the basis for more detailed future functional studies.

Từ khóa


Tài liệu tham khảo

10.1039/c3np70031c

10.1016/j.cell.2013.05.039

10.1016/S0047-6374(01)00419-5

10.1007/s10522-011-9354-3

10.1016/j.cell.2005.02.003

10.1016/j.cub.2012.07.024

10.1089/ars.2009.2598

10.1038/nrm2233

10.1126/science.279.5349.349

10.1016/0014-4827(61)90192-6

10.1016/j.cell.2007.07.003

10.1016/j.mad.2008.04.001

10.1038/sj.embor.7400352

10.1016/j.ceb.2011.07.006

10.1038/nature08980

10.1159/000351207

10.1002/bdrc.10022

10.1038/onc.2010.611

10.1186/1742-4933-5-5

10.1038/leu.2008.176

10.1073/pnas.2627983100

10.1038/nature02661

10.1016/j.exger.2003.11.011

10.1152/physiolgenomics.00049.2003

10.1186/1471-2105-3-23

10.1371/journal.pgen.0020115

10.1186/1471-2105-10-354

10.1038/nbt0604-656b

10.1089/cmb.2005.12.882

10.1093/bioinformatics/18.12.1585

10.1093/bioinformatics/18.12.1593

2002

2003

10.1080/01621459.1979.10481038

2003

10.1093/nar/30.4.e15

10.1093/bioinformatics/17.6.520

10.1073/pnas.1530509100

10.3389/fnins.2011.00008

10.1093/nar/gkr988

10.1038/75556

10.1109/tbme.2011.2164794

10.1371/journal.pone.0036911

10.1073/pnas.92.10.4337

10.1196/annals.1404.025

10.1006/excr.1995.1087

10.1093/bioinformatics/btp073

10.1039/c2mb05255e

10.1007/s10540-005-2742-7

10.1146/annurev.neuro.25.112701.142758

2012, Cold Spring Harbor Perspectives in Biology, 4

10.1371/journal.pone.0034863

10.1073/pnas.0802679105

10.1385/NMM:2:2:131

10.1128/mcb.00969-10

10.1016/j.cellsig.2008.11.001

10.1016/j.tiv.2010.08.003

10.1074/jbc.m112.437996

10.1038/sj.emboj.7600186

10.1042/bj20101247

10.1016/j.bbagen.2009.03.026

10.1016/j.brainresrev.2004.03.004

10.1007/s12020-014-0298-7

10.1038/35065000

2000, The American Journal of Physiology—Lung Cellular and Molecular Physiology, 279, L1005, 10.1152/ajplung.2000.279.6.L1005

10.1074/jbc.m113.530303

10.1074/jbc.c400557200

10.1016/j.abb.2011.12.022

10.1074/jbc.m108625200

10.1038/38525

10.1158/0008-5472.can-06-1600

10.1073/pnas.1111492108

10.1016/j.bbagen.2012.01.011

10.1111/j.1474-9726.2007.00321.x

10.1093/gerona/glq224

10.1016/j.exger.2013.12.004

10.1152/physiolgenomics.00028.2002

10.1371/journal.pone.0001385

2001, Journal of Applied Physiology, 91, 2686, 10.1152/jappl.2001.91.6.2686

1989, American Journal of Physiology—Endocrinology and Metabolism, 257, E567, 10.1152/ajpendo.1989.257.4.E567

2000, The American Journal of Physiology—Cell Physiology, 279, C611, 10.1152/ajpcell.2000.279.3.C611

10.1177/002215540004800506

10.1152/physrev.00031.2010

1992, Journals of Gerontology, 47, B71, 10.1093/geronj/47.3.B71

10.1111/j.1748-1716.2009.02010.x

10.1155/2013/249398

10.1677/joe-10-0209

10.1186/2042-6410-3-11

10.1016/j.nut.2009.10.013

10.1126/science.1172539

10.1126/science.1201940

10.1007/s00702-014-1293-0

10.1155/2014/648740

10.1038/nrg3553

10.1083/jcb.124.5.855

10.3109/03008207.2012.665970

10.1002/ijc.10105

10.1200/jco.2006.08.8583

10.1016/j.cell.2008.11.037

10.1242/jcs.108928

10.1016/j.yjmcc.2012.05.005

10.1038/ng.440

10.1001/jama.2010.1173

10.1016/j.neurobiolaging.2012.02.014

10.1111/j.1460-9568.2005.04555.x

10.1080/14734220310017212

10.1074/jbc.m109.096255

10.2174/13816128113196660709

10.1146/annurev.biochem.052308.114844

10.1038/nm1067

10.1016/j.nbd.2010.11.018

2009, Brain and Nerve, 61, 441

2013, American Journal of Neurodegenerative Disease, 2, 1

2011, Aging, 3, 1178, 10.18632/aging.100413

10.1111/j.1474-9726.2012.00795.x

10.1038/nrm1549

10.1007/s00125-007-0591-6

10.1046/j.1365-2184.2002.00232.x

10.1371/journal.pone.0005242