Implications of time‐series gene expression profiles of replicative senescence

Aging Cell - Tập 12 Số 4 - Trang 622-634 - 2013
You‐Mie Kim1, Hae‐Ok Byun1, Byul A Jee2, Hyunwoo Cho2, Yonghak Seo1, You‐Sun Kim3, Min Hi Park4, Hae‐Young Chung4, Hyun Goo Woo2, Gyesoon Yoon1
1Department of Biochemistry and Molecular Biology Ajou University School of Medicine Suwon 443‐721 Korea
2Department of Physiology
3Institute for Medical Sciences Ajou University School of Medicine Suwon 443‐721 Korea
4College of Pharmacy, Pusan National University, Pusan 609‐735, Korea

Tóm tắt

SummaryAlthough senescence has long been implicated in aging‐associated pathologies, it is not clearly understood how senescent cells are linked to these diseases. To address this knowledge gap, we profiled cellular senescence phenotypes and mRNA expression patterns during replicative senescence in human diploid fibroblasts. We identified a sequential order of gain‐of‐senescence phenotypes: low levels of reactive oxygen species, cell mass/size increases with delayed cell growth, high levels of reactive oxygen species with increases in senescence‐associated β‐galactosidase activity (SA‐β‐gal), and high levels of SA‐β‐gal activity. Gene expression profiling revealed four distinct modules in which genes were prominently expressed at certain stages of senescence, allowing us to divide the process into four stages: early, middle, advanced, and very advanced. Interestingly, the gene expression modules governing each stage supported the development of the associated senescence phenotypes. Senescence‐associated secretory phenotype–related genes also displayed a stage‐specific expression pattern with three unique features during senescence: differential expression of interleukin isoforms, differential expression of interleukins and their receptors, and differential expression of matrix metalloproteinases and their inhibitory proteins. We validated these phenomena at the protein level using human diploid fibroblasts and aging Sprague‐Dawley rat skin tissues. Finally, disease‐association analysis of the modular genes also revealed stage‐specific patterns. Taken together, our results reflect a detailed process of cellular senescence and provide diverse genome‐wide information of cellular backgrounds for senescence.

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Tài liệu tham khảo

Ahmed N., 2010, Frequency of metabolic syndrome in patients with type‐2 diabetes, J. Ayub Med. Coll. Abbottabad, 22, 139

10.1016/j.critrevonc.2007.09.001

10.1016/j.yexcr.2004.04.035

10.1007/s11357-008-9075-y

10.1002/jcb.21741

Campisi J., 2011, Cellular senescence: a link between cancer and age‐related degenerative disease?, Semin. Cancer Biol., 21, 354

10.1016/j.mad.2008.09.016

10.1002/pros.10204

10.1016/j.mad.2004.07.010

10.1016/j.exger.2005.04.010

10.1073/pnas.0409713102

10.1111/j.1749-6632.2002.tb02078.x

10.1016/j.molmed.2010.03.003

10.1289/ehp.96104s3557

10.1016/0959-437X(95)80016-6

10.1016/0014-4827(65)90211-9

10.1016/S1097-2765(04)00256-4

10.1016/S0021-9258(17)35859-3

10.1007/s00018-009-0034-2

10.1128/MCB.23.1.389-401.2003

10.1053/j.gastro.2010.01.054

10.1074/jbc.M211739200

10.1074/jbc.M110.120386

10.1006/bbrc.1995.1774

10.1016/0022-2836(92)90096-3

10.2337/db09-1003

10.1038/ncb2167

10.1016/S0531-5565(96)00164-7

10.1074/jbc.M109.088005

10.1016/j.arr.2011.06.004

10.1073/pnas.0905299106

10.1016/0047-6374(82)90085-9

10.1016/j.jalz.2010.11.002

10.1083/jcb.201009094

10.1016/S0167-4943(01)00218-7

10.1111/j.1474-9726.2008.00436.x

10.1016/0304-419X(91)90003-4

10.1101/gr.106849.110

10.1007/s00125-004-1605-2

10.1016/S0531-5565(03)00114-1

10.1186/1472-6823-10-4

10.2353/ajpath.2009.080703

10.1096/fj.00-0051com

10.1002/jcp.20753

Youdim M. B., 1993, The role of iron in senescence of dopaminergic neurons in Parkinson's disease, J. Neural Transm. Suppl., 40, 57

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Aging Cell

Tập 12 Số 4

622-634

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