WI-38 Senescence is Associated with Global and Site-specific Hypomethylation

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2014 Jul 27

PMID 25063771

Citations 15

Authors

Corinne Sidler

Rafal Woycicki

Igor Kovalchuk

Olga Kovalchuk

Affiliations

Soon will be listed here.

Abstract

Cellular senescence plays an important role in the age-dependent functional decline of organs and organ systems, as well as in age-related pathologies, such as cancer. Therefore, a better understanding of its underlying molecular mechanisms is crucial in the search for intervening measures. In this study, we considered the role of DNA methylation in senescence. We found that senescence is associated with global DNA hypomethylation, but also involves site-specific DNA hypo- and hypermethylation. In some cases, this differential methylation may affect gene expression and thereby modulate functional processes within cells. However, the majority of the CpG sites that were differentially methylated did not correspond with altered gene expression, suggesting that DNA methylation affects senescence by other means also, such as, for instance, genome stability.

Citing Articles

Significance of Circulating Cell-Free DNA Biomarkers in HBeAg-Negative Chronic Hepatitis B Virus Infection and Their Changes after Treatment Initiation.

Karakousis N, Chrysavgis L, Papatheodoridi A, Legaki A, Lembessis P, Cholongitas E Pathogens. 2023; 12(3).

PMID: 36986316 PMC: 10053129. DOI: 10.3390/pathogens12030394.

Genome-Wide Methylation Changes Associated with Replicative Senescence and Differentiation in Endothelial and Bone Marrow Mesenchymal Stromal Cells.

Giuliani A, Bacalini M, Ramini D, Mensa E, Giordani C, Xumerle L Cells. 2023; 12(2).

PMID: 36672222 PMC: 9857206. DOI: 10.3390/cells12020285.

Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts.

Gerasymchuk M, Robinson G, Kovalchuk O, Kovalchuk I Int J Mol Sci. 2022; 23(13).

PMID: 35806127 PMC: 9266450. DOI: 10.3390/ijms23137124.

CBX4 Regulates Replicative Senescence of WI-38 Fibroblasts.

Chen Y, Zhang X, Ko K, Hsueh M, Kraus V Oxid Med Cell Longev. 2022; 2022:5503575.

PMID: 35251476 PMC: 8890863. DOI: 10.1155/2022/5503575.

DNA methylation changes during long-term in vitro cell culture are caused by epigenetic drift.

Franzen J, Georgomanolis T, Selich A, Kuo C, Stoger R, Brant L Commun Biol. 2021; 4(1):598.

PMID: 34011964 PMC: 8134454. DOI: 10.1038/s42003-021-02116-y.

References

Vertino P, Sekowski J, Coll J, Applegren N, Han S, Hickey R . DNMT1 is a component of a multiprotein DNA replication complex. Cell Cycle. 2003; 1(6):416-23. DOI: 10.4161/cc.1.6.270. View

Safran M, Dalah I, Alexander J, Rosen N, Iny Stein T, Shmoish M . GeneCards Version 3: the human gene integrator. Database (Oxford). 2010; 2010:baq020. PMC: 2938269. DOI: 10.1093/database/baq020. View

Vogt M, Haggblom C, Yeargin J, Haas M . Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts. Cell Growth Differ. 1998; 9(2):139-46. View

Boyd J, Mathur S, Wang Y, Bateman R, Walley K . Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response. Cardiovasc Res. 2006; 72(3):384-93. DOI: 10.1016/j.cardiores.2006.09.011. View

Johansson A, Enroth S, Gyllensten U . Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan. PLoS One. 2013; 8(6):e67378. PMC: 3695075. DOI: 10.1371/journal.pone.0067378. View

Xia Y, Chen S, Wang Y, Mackman N, Ku G, Lo D . RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol. 1999; 19(11):7688-96. PMC: 84809. DOI: 10.1128/MCB.19.11.7688. View

Moskalev A, Aliper A, Smit-McBride Z, Buzdin A, Zhavoronkov A . Genetics and epigenetics of aging and longevity. Cell Cycle. 2014; 13(7):1063-77. PMC: 4013158. DOI: 10.4161/cc.28433. View

Fairweather D, Fox M, Margison G . The in vitro lifespan of MRC-5 cells is shortened by 5-azacytidine-induced demethylation. Exp Cell Res. 1987; 168(1):153-9. DOI: 10.1016/0014-4827(87)90424-1. View

Wilson V, Jones P . DNA methylation decreases in aging but not in immortal cells. Science. 1983; 220(4601):1055-7. DOI: 10.1126/science.6844925. View

10.

Leontieva O, Demidenko Z, Blagosklonny M . MEK drives cyclin D1 hyperelevation during geroconversion. Cell Death Differ. 2013; 20(9):1241-9. PMC: 3741510. DOI: 10.1038/cdd.2013.86. View

11.

Hayflick L, Moorhead P . The serial cultivation of human diploid cell strains. Exp Cell Res. 1961; 25:585-621. DOI: 10.1016/0014-4827(61)90192-6. View

12.

Melhuish T, Gallo C, Wotton D . TGIF2 interacts with histone deacetylase 1 and represses transcription. J Biol Chem. 2001; 276(34):32109-14. DOI: 10.1074/jbc.M103377200. View

13.

Loveys D, Streiff M, Kato G . E2A basic-helix-loop-helix transcription factors are negatively regulated by serum growth factors and by the Id3 protein. Nucleic Acids Res. 1996; 24(14):2813-20. PMC: 145994. DOI: 10.1093/nar/24.14.2813. View

14.

Reimand J, Arak T, Vilo J . g:Profiler--a web server for functional interpretation of gene lists (2011 update). Nucleic Acids Res. 2011; 39(Web Server issue):W307-15. PMC: 3125778. DOI: 10.1093/nar/gkr378. View

15.

Aherne C, McMorrow J, Kane D, FitzGerald O, Mix K, Murphy E . Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis. Mol Immunol. 2009; 46(16):3345-57. DOI: 10.1016/j.molimm.2009.07.019. View

16.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

17.

Lundblad V, Szostak J . A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989; 57(4):633-43. DOI: 10.1016/0092-8674(89)90132-3. View

18.

Reimand J, Kull M, Peterson H, Hansen J, Vilo J . g:Profiler--a web-based toolset for functional profiling of gene lists from large-scale experiments. Nucleic Acids Res. 2007; 35(Web Server issue):W193-200. PMC: 1933153. DOI: 10.1093/nar/gkm226. View

19.

Vanyushin B, Nemirovsky L, Klimenko V, Vasiliev V, BELOZERSKY A . The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia. 1973; 19(3):138-52. View

20.

Hahn W, Counter C, Lundberg A, Beijersbergen R, Brooks M, Weinberg R . Creation of human tumour cells with defined genetic elements. Nature. 1999; 400(6743):464-8. DOI: 10.1038/22780. View