Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress
Open accessAbstract
Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epigenetic mechanisms involving histone modifications that confer apoptosis resistance to senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative senescence display typical morphological features, express senescence-associated β-galactosidase, and increased levels of the tumor suppressor genes, p16, p21, and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous H2O2)-induced apoptosis in comparison to non-senescent (control) HDFs; this is associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and low expression of the pro-apoptotic gene, Bax. Cellular senescence is characterized by global increases in H4K20 trimethylation and decreases in H4K16 acetylation in association with increased activity of Suv420h2 histone methyltransferase (which targets H4K20), decreased activity of the histone acetyltransferase, Mof (which targets H4K16), as well as decreased total histone acetyltransferase activity. In contrast to Bax gene, chromatin immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this gene in senescent HDFs. These data indicate that both global and locus-specific histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in senescent fibroblasts, contributing to its apoptosis-resistant phenotype.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Senescent cells are resistant to apoptosis.
“Senescent cells, however, are resistant to apoptosis”
From p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling (2017) · cites this paper as Sanders et al, 2013
Induction of senescence appears protective against p53-dependent apoptosis and high oxidative stress.
“Indeed, induction of senescence appears protective against p53-dependent apoptosis [146] and high oxidative stress [254,255].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [255]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081 · see citing works
Fraga, M. F., Ballestar, E., Villar‐Garea, A., Boix-Chornet, M., Espada, J., Schotta, G., Bonaldi, T., Haydon, C. E., Ropero, S., Petrie, K. R., et al. (2005) · Nature Genetics · doi:10.1038/ng1531 · Cited by 1,926 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Incidence and Prevalence of Idiopathic Pulmonary Fibrosis
Raghu, G., Weycker, D., Edelsberg, J., Bradford, W. Z., & Oster, G. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200602-163oc · Cited by 1,310 · see citing works
Cytosol-to-membrane redistribution of Bax and Bcl-X L during apoptosis
Hsu, Y., Wolter, K. G., & Youle, R. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3668 · Cited by 1,134 · see citing works
HDAC family: What are the cancer relevant targets?
Witt, O., Deubzer, H. E., Milde, T., & Oehme, I. (2009) · Cancer Letters · doi:10.1016/j.canlet.2008.08.016 · Cited by 1,069 · see citing works
Human SIR2 deacetylates p53 and antagonizes PML/p53‐induced cellular senescence
Langley, E., Pearson, M., Faretta, M., Bauer, U., Frye, R. A., Minucci, S., Pelicci, P. G., & Kouzarides, T. (2002) · The EMBO Journal · doi:10.1093/emboj/21.10.2383 · Cited by 859 · see citing works
Epigenetics and aging: the targets and the marks
Fraga, M. F., & Esteller, M. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.05.008 · Cited by 690 · cited 4× · see citing works
“Chromatin structure is important in regulating gene expression; it is under dynamic changes throughout life span [11].”
BackgroundInfluentialHistone H4 lysine 16 acetylation regulates cellular lifespan
Dang, W., Steffen, K. K., Perry, R., Dorsey, J. A., Johnson, F. B., Shilatifard, A., Kaeberlein, M., Kennedy, B. K., & Berger, S. L. (2009) · Nature · doi:10.1038/nature08085 · Cited by 667 · see citing works
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629 · see citing works
(1995) · PubMed · Cited by 496 · see citing works
Enhanced Histone Acetylation and Transcription: A Dynamic Perspective
Clayton, A. L., Hazzalin, C. A., & Mahadevan, L. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.017 · Cited by 465 · see citing works
Oxidative Stress in Pulmonary Fibrosis
Kinnula, V. L., Fattman, C. L., Tan, R. J., & Oury, T. D. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200501-017pp · Cited by 437 · see citing works
The role of chondrocyte senescence in osteoarthritis
Price, J. S., Waters, J. G., Darrah, C., Pennington, C., Edwards, D. R., Donell, S. T., & Clark, I. M. (2002) · Aging Cell · doi:10.1046/j.1474-9728.2002.00008.x · Cited by 386 · see citing works
Characterization of a New Human Diploid Cell Strain, IMR-90
Nichols, W. W., Murphy, D. G., Cristofalo, V. J., Toji, L. H., Greene, A. E., & Dwight, S. (1977) · Science · doi:10.1126/science.841339 · Cited by 368 · see citing works
Evolving Concepts of Apoptosis in Idiopathic Pulmonary Fibrosis
Thannickal, V. J., & Horowitz, J. C. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200601-001tk · Cited by 361 · see citing works
Self-citationSIRT1, Is It a Tumor Promoter or Tumor Suppressor?
Deng, C. (2009) · International Journal of Biological Sciences · doi:10.7150/ijbs.5.147 · Cited by 322 · see citing works
Sharma, G. G., So, S., Gupta, A. K. D., Kumar, R., Cayrou, C., Avvakumov, N., Bhadra, U., PANDITA, R. K., Porteus, M. H., Chen, D. J., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01476-09 · Cited by 314 · see citing works
hMOF Histone Acetyltransferase Is Required for Histone H4 Lysine 16 Acetylation in Mammalian Cells
Taipale, M., Rea, S., Richter, K., Vilar, A., Lichter, P., Imhof, A., & Akhtar, A. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6798-6810.2005 · Cited by 313 · see citing works
NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs
Vaquero, A., Sternglanz, R., & Reinberg, D. (2007) · Oncogene · doi:10.1038/sj.onc.1210617 · Cited by 291 · see citing works
Replicative senescence of human fibroblast-like cells in culture
Cristofalo, V. J., & Pignolo, R. J. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.3.617 · Cited by 286 · see citing works
Chen, Q. M., Juping, L. I. U., & MERRETT, J. B. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3470543 · Cited by 280 · see citing works
CHEN, Q. M., LIU, J., & MERRETT, J. B. (2000) · Biochemical Journal · doi:10.1042/bj3470543 · Cited by 280 · see citing works
Waghray, M., Cui, Z., Horowitz, J. C., Subramanian, I. M., Martínez, F. J., Toews, G. B., & Thannickal, V. J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2882fje · Cited by 269 · see citing works
Self-citationOgryzko, V. V., Hirai, T. H., Russanova, V. R., Barbie, D. A., & Howard, B. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.5210 · Cited by 268 · see citing works
Cellular senescence in vivo: Its relevance in ageing and cardiovascular disease
Erusalimsky, J. D., & Kurz, D. J. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.04.010 · Cited by 252 · see citing works
Sarg, B., Koutzamani, E., Helliger, W., Rundquist, I., & Lindner, H. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205166200 · Cited by 252 · see citing works
Epigenetic alterations in aging
Gonzalo, S. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00238.2010 · Cited by 249 · see citing works
Altered DNA Methylation Profile in Idiopathic Pulmonary Fibrosis
Sanders, Y. Y., Ambalavanan, N., Halloran, B., Zhang, X., Liu, H., Crossman, D. K., Bray, M., Zhang, K., Thannickal, V. J., & Hagood, J. S. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201201-0077oc · Cited by 242 · see citing works
Self-citationKrishnan, V., Chow, M. Z. Y., Wang, Z., Zhang, L., Liu, B., Liu, X., & Zhou, Z. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102789108 · Cited by 236 · see citing works
Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis.
Sanders, Y., Pardo, A., Selman, M., Nuovo, G., Tollefsbol, T., Siegal, G., & Hagood, J. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0322oc · Cited by 234 · see citing works
Self-citationDevelopmental roles of the histone lysine demethylases
Nottke, A. C., Colaiácovo, M. P., & Shi, Y. (2009) · Development · doi:10.1242/dev.020966 · Cited by 225 · see citing works
Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes
Campisi, J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00152-3 · Cited by 218 · see citing works
Defining cellular senescence in IMR-90 cells: a flow cytometric analysis.
Sherwood, S. W., Rush, D. F., Ellsworth, J. L., & SCHIMKE, R. T. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.23.9086 · Cited by 200 · see citing works
The controversial world of sirtuins
Dang, W. (2012) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2012.08.003 · Cited by 153 · see citing works
Enhanced Myofibroblastic Differentiation and Survival in Thy-1(−) Lung Fibroblasts
Sanders, Y. Y., Kumbla, P. A., & Hagood, J. S. (2006) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2006-0178oc · Cited by 153 · see citing works
Self-citationRyu, S. J., Oh, Y. S., & Park, S. C. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402091 · Cited by 114 · see citing works
Epigenetic Regulation of Thy-1 by Histone Deacetylase Inhibitor in Rat Lung Fibroblasts
Sanders, Y. Y., Tollefsbol, T. O., Varisco, B. M., & Hagood, J. S. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2010-0154oc · Cited by 106 · see citing works
Self-citationDistinct dynamics and distribution of histone methyl-lysine derivatives in mouse development
Biron, V. L., McManus, K. J., Hu, N., Hendzel, M. J., & Underhill, D. A. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.08.038 · Cited by 86 · see citing works
Hajji, N., Wallenborg, K., Engskog‐Vlachos, P., Füllgrabe, J., Hermanson, O., & Joseph, B. (2010) · Oncogene · doi:10.1038/onc.2009.505 · Cited by 86 · see citing works
Monti, D., Salvioli, S., Capri, M., Malorni, W., Straface, E., Cossarizza, A., Botti, B., Piacentini, M., Baggio, G., Barbi, C., et al. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00220-7 · Cited by 86 · see citing works
Ryu, S. J., An, H. J., Oh, Y. S., Choi, H. R., Ha, M., & Park, S. C. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.96 · Cited by 71 · see citing works
Chromatin modifications: The driving force of senescence and aging?
DiMauro, T., & David, G. (2009) · Aging · doi:10.18632/aging.100023 · Cited by 56 · see citing works
Stem Cell Senescence and Regenerative Paradigms
Beltrami, A. P., Cesselli, D., & Beltrami, C. A. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.262 · Cited by 54 · see citing works
Tsang, L. W. K., Hu, N., & Underhill, D. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014447 · Cited by 37 · see citing works
Al‐Khalaf, H. H., & Aboussekhra, A. (2012) · AGE · doi:10.1007/s11357-011-9378-2 · Cited by 19 · see citing works
Silencing of the CKIIα and CKIIα' genes during cellular senescence is mediated by DNA methylation
Kim, E., Kang, J., Rho, Y.-H., Kim, Y., Kim, D. S., & Bae, Y. (2008) · Gene · doi:10.1016/j.gene.2008.10.020 · Cited by 14 · see citing works
Kim, S. Y., Ryu, S. J., Kang, H. T., Choi, H. R., & Park, S. C. (2011) · APOPTOSIS · doi:10.1007/s10495-011-0612-2 · Cited by 13 · see citing works
Lee, Y., Lee, N., Bhattarai, G., Hwang, P.-H., Kim, T., Jhee, E., & Yi, H. (2009) · Biogerontology · doi:10.1007/s10522-009-9244-0 · Cited by 11 · see citing works
Flagged first, then by citations
2 of the 53 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059 · see citing works
Senescence and apoptosis: dueling or complementary cell fates?
Childs, B. G., Baker, D. J., Kirkland, J. L., Campisi, J., & van Deursen, J. M. (2014) · The EMBO Reports · doi:10.15252/embr.201439245 · Cited by 915 · see citing works
Exploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867 · see citing works
TGF-β1 Signaling and Tissue Fibrosis
Kim, K. K., Sheppard, D., & Chapman, H. A. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022293 · Cited by 800 · see citing works
Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance
Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., Meldrum, E., Sanders, Y. Y., & Thannickal, V. J. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008182 · Cited by 686 · see citing works
Self-citationContributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442 · see citing works
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 410 · see citing works
Mechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
Yosef, R., Pilpel, N., Papismadov, N., Gal, H., Ovadya, Y., Vadai, E., Miller, S., Porat, Z., Ben‐Dor, S., & Krizhanovsky, V. (2017) · The EMBO Journal · doi:10.15252/embj.201695553 · Cited by 293 · see citing works
Cellular Senescence in Neurodegenerative Diseases
Martínez‐Cué, C., & Rueda, N. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00016 · Cited by 285 · see citing works
Physiological and pathological consequences of cellular senescence
Burton, D. G. A., & Krizhanovsky, V. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1691-3 · Cited by 253 · see citing works
Inflammageing and metaflammation: The yin and yang of type 2 diabetes
Prattichizzo, F., Nigris, V. D., Spiga, R., Mancuso, E., Sala, L. L., Antonicelli, R., Testa, R., Procopio, A. D., Olivieri, F., & Ceriello, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.003 · Cited by 249 · see citing works
Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases
Song, S., Lam, E. W.-F., Tchkonia, T., Kirkland, J. L., & Sun, Y. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.008 · Cited by 195 · see citing works
“Simultaneously, expression of the proapoptotic factor Bax is restrained by the repressive histone mark H4K20me3, in line with increased activity of Suv420h2 histone methyltransferase, which targets H4K20 [75].”
BackgroundCellular senescence in cancer: from mechanisms to detection
Ou, H., Hoffmann, R. J., González‐López, C., Doherty, G. J., Korkola, J. E., & Muñoz‐Espín, D. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12807 · Cited by 198 · see citing works
Regulation of Survival Networks in Senescent Cells: From Mechanisms to Interventions
Soto-Gamez, A., Quax, W. J., & Demaria, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.036 · Cited by 175 · see citing works
The Metabolic Impact on Histone Acetylation and Transcription in Ageing
Peleg, S., Feller, C., Ladurner, A. G., & Imhof, A. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.05.008 · Cited by 178 · see citing works
Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts
Walker, C. J., Crocini, C., Ramirez, D., Killaars, A. R., Grim, J. C., Aguado, B. A., Clark, K., Allen, M. A., Dowell, R. D., Leinwand, L. A., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00709-w · Cited by 174 · see citing works
Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
Hu, L., Li, H., Zi, M., Li, W., Liu, J., Yang, Y., Zhou, D., Kong, Q., Zhang, Y., & He, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822816 · Cited by 167 · see citing works
Mechanisms of Lung Fibrosis Resolution
Glasser, S. W., Hagood, J. S., Wong, S. S., Taype, C. A., Madala, S. K., & Hardie, W. D. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.01.018 · Cited by 148 · see citing works
The DNA Damage Response in Neurons: Die by Apoptosis or Survive in a Senescence-Like State?
Fielder, E., von Zglinicki, T., & Jurk, D. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161221 · Cited by 126 · see citing works
Vilgelm, A. E., Pawlikowski, J. S., Liu, Y., Hawkins, O. E., Davis, T. A., Smith, J., Weller, K. P., Horton, L. W., McClain, C. M., Ayers, G. D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2405 · Cited by 115 · see citing works
Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease
Li, Y., Zhao, J., & Hölscher, C. (2017) · CNS Drugs · doi:10.1007/s40263-017-0451-y · Cited by 115 · see citing works
Cell senescence and fibrotic lung diseases
Liu, R.-M., & Liu, G. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110836 · Cited by 115 · see citing works
Self-citationExamining the Roles of H3K4 Methylation States with Systematically Characterized Antibodies
Shah, R. N., Grzybowski, A. T., Cornett, E. M., Johnstone, A. L., Dickson, B. M., Boone, B. A., Cheek, M. A., Cowles, M. W., Maryanski, D. N., Meiners, M. J., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.015 · Cited by 117 · see citing works
Mechanistic links between aging and lung fibrosis
Thannickal, V. J. (2013) · Biogerontology · doi:10.1007/s10522-013-9451-6 · Cited by 106 · see citing works
Self-citationFibroblast Senescence in Idiopathic Pulmonary Fibrosis
Lin, Y., & Xu, Z. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.593283 · Cited by 104 · see citing works
Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Luan, Y., Zhu, X., Jiao, Y., Liu, H., Huang, Z., Pei, J., Xu, Y., Yang, Y., & Ren, K. (2024) · Cell Death Discovery · doi:10.1038/s41420-023-01792-5 · Cited by 106 · see citing works
Self-citationEvidence and perspectives of cell senescence in neurodegenerative diseases
Si, Z., Sun, L., & Wang, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111327 · Cited by 105 · see citing works
Impaired Myofibroblast Dedifferentiation Contributes to Nonresolving Fibrosis in Aging
Kato, K., Logsdon, N. J., Shin, Y.-J., Palumbo, S., Knox, A., Irish, J. D., Rounseville, S. P., Rummel, S. R., Mohamed, M., Ahmad, K., et al. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0092oc · Cited by 100 · see citing works
Self-citationFibronectin on the Surface of Extracellular Vesicles Mediates Fibroblast Invasion
Chanda, D., Otoupalova, E., Hough, K. P., Locy, M. L., Bernard, K. F., Deshane, J. S., Sanderson, R. D., Mobley, J. A., & Thannickal, V. J. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2018-0062oc · Cited by 97 · see citing works
Self-citationThe Histone Code of Senescence
Paluvai, H., Giorgio, E. D., & Brancolini, C. (2020) · Cells · doi:10.3390/cells9020466 · Cited by 94 · see citing works
Redox mechanisms in age-related lung fibrosis
Kurundkar, A., & Thannickal, V. J. (2016) · Redox Biology · doi:10.1016/j.redox.2016.06.005 · Cited by 88 · see citing works
Self-citationBai, L., Bernard, K., Tang, X., Hu, M., Horowitz, J. C., Thannickal, V. J., & Sanders, Y. Y. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2018-0180oc · Cited by 88 · see citing works
Self-citationMechanisms of Superoxide Signaling in Epigenetic Processes: Relation to Aging and Cancer
Afanasʹev, I. B. (2015) · Aging and Disease · doi:10.14336/ad.2014.0924 · Cited by 84 · see citing works
Emerging insights in senescence: pathways from preclinical models to therapeutic innovations
Mansfield, L., Ramponi, V., Gupta, K., Stevenson, T., Mathew, A. B., Barinda, A. J., Herbstein, F., & Morsli, S. (2024) · npj Aging · doi:10.1038/s41514-024-00181-1 · Cited by 91 · see citing works
Epigenetic mechanisms regulate NADPH oxidase-4 expression in cellular senescence.
Sanders, Y., Liu, H., Liu, G., & Thannickal, V. (2015) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2014.12.008 · Cited by 77 · see citing works
Self-citationSmyd3-associated regulatory pathways in cancer
Giakountis, A., Moulos, P., Sarris, M. E., Hatzis, P., & Talianidis, I. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.08.008 · Cited by 74 · see citing works
Oxidative stress-mediated alterations in histone post-translational modifications
García‐Giménez, J. L., Garcés, C., Mateo, C. R., & Pallardó, F. V. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.027 · Cited by 74 · see citing works
Zhou, C., Guo, H., Willson, A. K., Yuan, L., Jones, H. M., Gehrig, P. A., Sheng, X., Zhang, L., Clark, L. H., & Bae-Jump, V. L. (2020) · PubMed Central · doi:10.17615/2xfe-5p09 · Cited by 72 · see citing works
Virmani, A., Pinto, L., Bauermann, O., Zerelli, S., Diedenhofen, A., Binienda, Z. K., Ali, S. F., & van der Leij, F. R. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9238-7 · Cited by 69 · see citing works
Liu, Y., Lomeli, I., & Kron, S. J. (2024) · Cells · doi:10.3390/cells13151281 · Cited by 72 · see citing works
Epigenetic regulation in cell senescence
Cheng, L.-Q., Zhang, Z.-Q., Chen, H.-Z., & Liu, D.-P. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1581-x · Cited by 64 · see citing works
Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword
Battram, A. M., Bachiller, M., & Martín-Antonio, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124346 · Cited by 63 · see citing works
Helbling-Leclerc, A., Garcin, C., & Rosselli, F. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00764-5 · Cited by 54 · see citing works
Rehan, M., Kurundkar, D., Kurundkar, A., Logsdon, N. J., Smith, S. R., Chanda, D., Bernard, K. F., Sanders, Y. Y., Deshane, J. S., Dsouza, K. G., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00027-5 · Cited by 56 · see citing works
Self-citationSalminen, A. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04520-x · Cited by 56 · see citing works
Liu, R., Li, Y., Zheng, Q., Ding, M., Zhou, H., & Li, X. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.10.023 · Cited by 54 · see citing works
Rodríguez‐Sureda, V., García, Á. V., Sánchez, O., Audı́, L., & Domı́nguez, C. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/509241 · Cited by 54 · see citing works
Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts
Gerasymchuk, M., Robinson, G. I., Kovalchuk, O., & Kovalchuk, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137124 · Cited by 50 · see citing works
Genetic background, epigenetic factors and dietary interventions which influence human longevity
Costa, D., Scognamiglio, M., Fiorito, C., Benincasa, G., & Claudio Napoli, A. (2019) · Biogerontology · doi:10.1007/s10522-019-09824-3 · Cited by 45 · see citing works
Cellular and Molecular Mechanisms in Idiopathic Pulmonary Fibrosis
Zhang, Y., & Wang, J. (2023) · Advances in respiratory medicine · doi:10.3390/arm91010005 · Cited by 44 · see citing works
Šalovská, B., Kondelová, A., Pimková, K., Liblova, Z., Přibyl, M., Fabrik, I., Bártek, J., Vajrychová, M., & Hodný, Z. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102212 · Cited by 44 · see citing works
Klepacki, H., Kowalczuk, K., Łepkowska, N., & Hermanowicz, J. M. (2025) · Cells · doi:10.3390/cells14130942 · Cited by 44 · see citing works
The Role of Epigenetics in the Fibrotic Processes Associated with Glaucoma
McDonnell, F. S., O'Brien, C. J., & Wallace, D. (2014) · Journal of Ophthalmology · doi:10.1155/2014/750459 · Cited by 44 · see citing works
Epigenetic remodeling under oxidative stress: Mechanisms driving tumor metastasis
Peng, P., Qin, S., Li, L., He, Z., Li, B., Nice, E. C., Zhou, L., & Lei, Y. (2024) · MedComm – Oncology · doi:10.1002/mog2.70000 · Cited by 41 · see citing works
The role of Bcl-2 family proteins in pulmonary fibrosis
Safaeian, L., Abed, A., & Vaseghi, G. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.07.029 · Cited by 39 · see citing works
Bcl-xL as a Modulator of Senescence and Aging
Mas‐Bargues, C., Borrás, C., & Viña, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041527 · Cited by 38 · see citing works
The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation
Ibragimova, M., Kussainova, A., Aripova, A., Bersimbaev, R. I., & Bulgakova, O. (2024) · Cells · doi:10.3390/cells13060550 · Cited by 36 · see citing works
Targeted elimination of senescent Ras-transformed cells by suppression of MEK/ERK pathway
Kochetkova, E. Y., Blinova, G. I., Bystrova, O. A., Martynova, M. G., Pospelov, V. A., & Pospelova, T. V. (2017) · Aging · doi:10.18632/aging.101325 · Cited by 34 · see citing works
Soto-Gamez, A., Wang, Y., Zhou, X., Seras, L., Quax, W. J., & Demaria, M. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.10.038 · Cited by 33 · see citing works
Exploring cellular senescence in the musculoskeletal system: Any insights for biomarkers discovery?
Gerosa, L., Malvandi, A. M., Malavolta, M., Provinciali, M., & Lombardi, G. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101943 · Cited by 32 · see citing works
Zhang, X., Liu, H., Zhou, J. Q., Krick, S., Barnes, J. W., Thannickal, V. J., & Sanders, Y. Y. (2021) · Theranostics · doi:10.7150/thno.62760 · Cited by 32 · see citing works
Self-citationChen, J., Chen, K., Wang, L., Luo, J., Zheng, Q., & He, Y. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04972-w · Cited by 32 · see citing works
Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic
Al-Mansour, F. S. H., Alraddadi, A. M., He, B., Saleh, A., Poblocka, M., Alzahrani, W., Cowley, S. M., & Macip, S. (2023) · Aging · doi:10.18632/aging.204616 · Cited by 30 · see citing works
An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence
Saitou, M., Lizardo, D. Y., Taşkent, R. Ö., Millner, A., Gökçümen, Ö., & Atilla‐Gokcumen, G. E. (2018) · Molecular Omics · doi:10.1039/c8mo00099a · Cited by 29 · see citing works
Solari, N. E. F., Belforte, F. S., Canedo, L., Videla-Richardson, G. A., Espinosa, J. M., Rossi, M., Serna, E., Riudavets, M. A., Martinetto, H., Sevlever, G. E., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3159 · Cited by 26 · see citing works
Chen, B., Chai, Q., Xu, S., Li, Q., Wu, T., Chen, S., & Wu, L. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.111070 · Cited by 27 · see citing works
The role of immunosuppressive myofibroblasts in the aging process and age-related diseases
Salminen, A. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02360-1 · Cited by 26 · see citing works
Suzuki, T., Kropski, J. A., Chen, J., Carrier, E. J., Chen, X., Sherrill, T. P., Winters, N. I., Camarata, J. E., Polosukhin, V. V., Han, W., et al. (2022) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.202106-1503oc · Cited by 24 · see citing works
Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence
Barriuso, D., Alvarez-Frutos, L., Gutiérrez, L. G., Motiño, O., Kroemer, G., Palacios, R., & Senovilla, L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076374 · Cited by 23 · see citing works
Autoimmunity in centenarians. A paradox
Anaya, J., Lozada-Martínez, I. D., Torres, I. P., & Shoenfeld, Y. (2024) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2024.100237 · Cited by 23 · see citing works
Li, N., Yuan, Q., Cao, X., Zhang, Y., Min, Z.-L., Xu, S., Yu, Z., Cheng, J., Zhang, C., & Hu, X. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.16 · Cited by 23 · see citing works
Marzetti, E., Calvani, R., Landi, F., Coelho‐Júnior, H. J., & Picca, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137305 · Cited by 24 · see citing works
Carpenter, V. J., Patel, B. B., Riccardo Autorino, B., Smith, S. C., Gewirtz, D. A., & Saleh, T. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188424 · Cited by 17 · see citing works
Recent Advances in Senolysis for Age-Related Diseases
Aratani, S., & Nakanishi, M. (2023) · Physiology · doi:10.1152/physiol.00003.2023 · Cited by 16 · see citing works
p21 facilitates chronic lung inflammation via epithelial and endothelial cells
Levi, N., Papismadov, N., Majewska, J., Roitman, L., Wigoda, N., Eilam, R., Tsoory, M., Rotkopf, R., Ovadya, Y., Akiva, H., et al. (2023) · Aging · doi:10.18632/aging.204622 · Cited by 15 · see citing works
Cortese, F. A. B., & Santostasi, G. (2015) · Rejuvenation Research · doi:10.1089/rej.2015.1763 · Cited by 15 · see citing works
Bjørneset, J., Blévin, P., Bjørnstad, P. M., Dalmo, R. A., Goksøyr, A., Harju, M., Limonta, G., Panti, C., Rikardsen, A. H., Sundaram, A. Y. M., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.107915 · Cited by 15 · see citing works
Key changes in chromatin mark mammalian epidermal differentiation and ageing
Dube, C. T., Jahan, F. R. S., & Lim, C. Y. (2021) · Epigenetics · doi:10.1080/15592294.2021.1917812 · Cited by 15 · see citing works
Schuler, N., Timm, S., & Rübe, C. E. (2017) · Stem Cells · doi:10.1002/stem.2768 · Cited by 15 · see citing works
Baicalein reduces the occurrence of cirrhotic endotoxemia by reducing intestinal mucosal apoptosis
Liu, Y., Ye, F., Zou, W., Sun, Y., Wang, R., Han, P.-P., Zhang, Z., Yang, X., & Liu, X. (2015) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-015-0682-8 · Cited by 14 · see citing works
Zhang, K., Chen, C., Liu, Y., Chen, H., & Liu, J. (2014) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12328 · Cited by 14 · see citing works
Cellular Senescence in Liver Cancer: How Dying Cells Become “Zombie” Enemies
Gazzillo, A., Volponi, C., Soldani, C., Polidoro, M. A., Franceschini, B., Lleò, A., Bonavita, E., & Donadon, M. (2023) · Biomedicines · doi:10.3390/biomedicines12010026 · Cited by 14 · see citing works
Torma, F., Bori, Z., Koltai, E., Felszeghy, K., Vácz, G., Koch, L. G., Britton, S. L., Boldogh, I. R., & Radak, Z. O. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2014.07.003 · Cited by 11 · see citing works
The ING1a model of rapid cell senescence
Bertschmann, J., Thalappilly, S., & Riabowol, K. T. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.06.004 · Cited by 11 · see citing works
Interrogating the regulatory epigenome of cellular senescence
Thanos, D.-F., Ntintas, O. A., Athanasiadis, E. I., Papaspyropoulos, A., Petty, R., & Gorgoulis, V. G. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05848-w · Cited by 10 · see citing works
Polzer, O., Kinloch, E., & Fitzsimons, C. P. (2025) · Aging Brain · doi:10.1016/j.nbas.2025.100141 · Cited by 10 · see citing works
Liu, W., Fan, B., Fang, T., Li, H., Zhang, J., Liu, B., & Liu, Z. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.08.010 · Cited by 10 · see citing works
Role of NSD1 in H2O2-induced GSTM3 suppression
Chu, G., Li, Y., Dong, X., Liu, J., & Zhao, Y. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.08.026 · Cited by 9 · see citing works
Fan, G., Xie, T., Tan, Q., Lou, N., Wang, S., Han, X., & Shi, Y. (2023) · iScience · doi:10.1016/j.isci.2023.107894 · Cited by 7 · see citing works
Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells
Yamashita, S., Okamoto, M., Mendonca, M., Fujiwara, N., Kitamura, E., Chang, C.-S., Brueckner, S., Shindo, S., Kuriki, N., Cooley, M. A., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179600 · Cited by 8 · see citing works
Could senescence phenotypes strike the balance to promote tumor dormancy?
Chiu, F.-Y., Kvadas, R. M., Mheidly, Z., Shahbandi, A., & Jackson, J. G. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10089-z · Cited by 8 · see citing works
ΔNp63α-mediated epigenetic regulation in keratinocyte senescence
Kuang, L., & Li, C. (2023) · Epigenetics · doi:10.1080/15592294.2023.2173931 · Cited by 8 · see citing works
Senescence, the Janus of Lung Injury and Repair
Wallach‐Dayan, S. B., & Rojas, M. M. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0022ed · Cited by 8 · see citing works
An Integrated Pathogenetic Model of Primary Biliary Cholangitis
Kouroumalis, E., Tsomidis, I., & Voumvouraki, A. (2025) · Livers · doi:10.3390/livers5020015 · Cited by 7 · see citing works
Zhong, B., Zhou, J. Q., Lyu, X., Liu, H., Yuan, K., Guo, M., Duncan, S. R., & Sanders, Y. Y. (2024) · The Journal of Immunology · doi:10.4049/jimmunol.2400106 · Cited by 7 · see citing works
Self-citationPinto, A. V. L. (2014) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000132 · Cited by 6 · see citing works
Türkoğlu, B., & Mansuroğlu, B. (2024) · Life · doi:10.3390/life14091070 · Cited by 7 · see citing works
- Authors
- Sanders, Y. Y., Liu, H., Zhang, X., Hecker, L., Bernard, K., Desai, L., Liu, G., & Thannickal, V. J.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Sanders, Yan Y.
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2013
- Volume
- 1
- Issue
- 1
- Pages
- 8-16
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC3757696
- OpenAlex
- W1999206742
- Cited by
- 138
- References
- 53
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 11 · 2021: 14 · 2020: 17 · 2019: 4 · 2018: 9 · 2017: 11 · 2016: 6 · 2015: 9 · 2014: 13 · 2013: 2
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association (09SDG2260095)
- Coalition for Pulmonary Fibrosis
- Pulmonary Fibrosis Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL067967, T32HL105346)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- cellular senescence, replicative senescence, apoptosis resistance, oxidative stress, histone modifications, H4K20 trimethylation, H4K16 acetylation, Bcl-2, Bax, human diploid fibroblasts, epigenetic regulation
- MeSH terms
- Cells, Cultured, Fibroblasts, Gene Expression Regulation, Histones, Humans, Hydrogen Peroxide, Cellular Senescence, Apoptosis, Oxidative Stress, Proto-Oncogene Proteins c-bcl-2, Epigenesis, Genetic, bcl-2-Associated X Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
