Chromatin basis of the senescence-associated secretory phenotype
Open accessAbstract
Cellular senescence is a stable cell growth arrest. Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed senescence-associated secretory phenotype (SASP). The SASP exerts a range of functions in both normal health and pathology, which is possibly best characterized in cancers and physical aging. Recent studies demonstrated that chromatin is instrumental in regulating the SASP both through nuclear transcription and via the innate immune cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in the cytoplasm. Here, we will review these regulatory mechanisms, with an emphasis on most recent developments in the field. We will highlight the challenges and opportunities in developing intervention approaches, such as targeting chromatin regulatory mechanisms, to alter the SASP as an emerging approach to combat cancers and achieve healthy aging.
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Changes in the higher-order structure of chromatin contribute to the development of SASP or SASP-like inflammatory gene expression.
“Recent studies by our group and others have suggested that changes in the higher-order structure of chromatin contribute to the development of SASP or SASP-like inflammatory gene expression (11, 19–22).”
From Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment (2023) · cites this paper as [22]
Targeting the cGAS-STING axis with the small-molecule STING inhibitor H-151 had a SASP-suppressing, senomorphic effect and led to reduced lung pathology and prolonged survival in a human ACE2-transgenic mouse model of COVID-19.
“Targeting of the cGAS–STING axis, which induces type I interferons and other SASP factors, with the small-molecule STING inhibitor H-151 had a SASP-suppressing, senomorphic effect28,121,128,129 and led to reduced lung pathology and prolonged survival in a human ACE2-transgenic mouse model of COVID-19 (ref.59).”
From COVID-19 and cellular senescence (2023) · cites this paper as [129]
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Senescence as a therapeutically relevant response to CDK4/6 inhibitors
Wagner, V., & Gil, J. (2020) · Oncogene · doi:10.1038/s41388-020-1354-9 · Cited by 148 · see citing works
Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance
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The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Sumter, T. F., Xian, L., Huso, T. H., Koo, M., Chang, Y.-T., Almasri, T. N., Chia, L., Inglis, C., Reid, D., & Resar, L. M. S. (2016) · Current Molecular Medicine · doi:10.2174/1566524016666160316152147 · Cited by 120 · see citing works
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Large-scale chromatin organization: the good, the surprising, and the still perplexing
Belmont, A. S. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.10.002 · Cited by 104 · see citing works
HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence
Sofiadis, K., Nikolić, M., Kargapolova, Y., Josipović, N., Zirkel, A., Papadakis, A., Papadionysiou, I., Loughran, G., Keanes, J., Michel, A., et al. (2021) · Molecular Systems Biology · doi:10.15252/msb.20209760 · Cited by 102 · see citing works
Rosin, L. F., Nguyen, S. C., & Joyce, E. F. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007393 · Cited by 98 · see citing works
Nuclear pore density controls heterochromatin reorganization during senescence
Boumendil, C., Hari, P., Olsen, K. C. F., Acosta, J. C., & Bickmore, W. A. (2019) · Genes & Development · doi:10.1101/gad.321117.118 · Cited by 89 · see citing works
Han, X., Chen, H., Gong, H., Tang, X., Huang, N., Xu, W., Tai, H., Zhang, G., Zhao, T., Gong, C., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010734 · Cited by 80 · see citing works
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence
Olan, I., Parry, A. J., Schoenfelder, S., Narita, M., Ito, Y., Chan, A. S. L., Slater, G. S. C., Bihary, D., Bando, M., Shirahige, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19878-4 · Cited by 76 · see citing works
DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A
Leon, K. E., Buj, R., Lesko, E., Dahl, E. S., Chen, C.-W., Tangudu, N. K., Imamura-Kawasawa, Y., Kossenkov, A. V., Hobbs, R. P., & Aird, K. M. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202008101 · Cited by 70 · see citing works
Topoisomerase 1 cleavage complex enables pattern recognition and inflammation during senescence
Zhao, B., Liu, P., Fukumoto, T., Nacarelli, T., Fatkhutdinov, N., Wu, S., Lin, J., Aird, K. M., Tang, H., Liu, Q., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14652-y · Cited by 67 · see citing works
Self-citationXue, H., Zhao, B., Zhou, W., Liu, H., Fukumoto, T., Gabrilovich, D. I., & Zhang, R. (2020) · iScience · doi:10.1016/j.isci.2020.102016 · Cited by 62 · see citing works
Self-citationIwasaki, O., Tanizawa, H., Kim, K.-D., Kossenkov, A., Nacarelli, T., Tashiro, S., Majumdar, S., Showe, L. C., Zhang, R., & Noma, K.-I. (2019) · Nature Communications · doi:10.1038/s41467-019-13604-5 · Cited by 58 · see citing works
Self-citationKolovos, P., Georgomanolis, T., Köferle, A., Larkin, J. D., Brant, L., Nikolicć, M., Gusmao, E. G., Zirkel, A., Knoch, T., van Ijcken, W. F., et al. (2016) · Genome Research · doi:10.1101/gr.210005.116 · Cited by 51 · see citing works
From single genes to entire genomes: the search for a function of nuclear organization
Pueschel, R., Coraggio, F., & Meister, P. (2016) · Development · doi:10.1242/dev.129007 · Cited by 49 · see citing works
Comoglio, F., Park, H. J., Schoenfelder, S., Barozzi, I., Bode, D., Fraser, P., & Green, A. R. (2018) · Genome Research · doi:10.1101/gr.227272.117 · Cited by 41 · see citing works
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Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00672-x · Cited by 164 · see citing works
“The composition of SASP varies across different cell types and depends on the specific senescence-inducing stimuli, but most of the factors are regulated by NF-κB pathway, at least partially via cGAS-STING activation [13, 18, 84, 85].”
BackgroundCOVID-19 and cellular senescence
Schmitt, C. A., Tchkonia, T., Niedernhofer, L. J., Robbins, P. D., Kirkland, J. L., & Lee, S. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00785-2 · Cited by 153 · see citing works
Jurcău, M. C., Jurcău, A., Cristian, A., Hogea, V. O., Diaconu, R. G., & Nunkoo, V. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910535 · Cited by 90 · see citing works
“Inflammasomes are multiprotein complexes assembled in the cytosol, consisting of a sensor protein, the adapter apoptosis-associated speck-like protein (ASC), and procaspase-1 [272].”
BackgroundThe role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression
Dasgupta, N., Arnold, R., Equey, A., Gandhi, A., & Adams, P. D. (2024) · npj Aging · doi:10.1038/s41514-024-00172-2 · Cited by 86 · see citing works
“In addition to the cGAS- STING-NF-κ B pathway, several other factors, including DNA damage signaling, C/EBPß, GATA4, and pathways such as p38 MAP-kinase, mTOR, JAK-STAT, and Notch, regulate SASP 5,13,14 .”
BackgroundOxidative Stress: Molecular Mechanisms, Diseases, and Therapeutic Targets
Qin, Y., Qian, C., Li, W., Wang, Q., Sheng, Q., Chen, Z., Zhang, W., Li, W., Ge, G., Yan, Z., et al. (2026) · MedComm · doi:10.1002/mco2.70600 · Cited by 59 · see citing works
Dynamic 3D genome reorganization during senescence: defining cell states through chromatin
Shaban, H. A., & Gasser, S. M. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01197-y · Cited by 55 · see citing works
“The characteristic features of this state are cell cycle arrest or exit, highly visible chromatin rearrangements, and enhanced secretion or SASP [11] (Fig.”
Oxidative stress and cellular senescence: Roles in tumor progression and therapeutic opportunities
Jin, P., Feng, X., Huang, C., Li, J., Wang, H. Z., Wang, X., Li, L., & Ma, L. (2024) · MedComm – Oncology · doi:10.1002/mog2.70007 · Cited by 57 · see citing works
Ferroptosis in the ageing retina: A malevolent fire of diabetic retinopathy
Li, S., Zhao, N., Dong, W., Pu, N., Hao, X.-N., Huang, J., Peng, G.-H., & Tao, Y. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102142 · Cited by 45 · see citing works
Self-citationAutophagy and senescence: the molecular mechanisms and implications in liver diseases
Li, Q., Lin, Y., Liang, G., Xiao, N., Zhang, H., Yang, X., Yang, J., & Liu, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316880 · Cited by 43 · see citing works
“DNA methylation, chromatin remodeling, and RNA modification are epigenetic alterations that commonly occur in senescent cells [116,117].”
BackgroundAdem, Y., Aprile, D., Alessio, N., Peluso, G., Bernardo, G. D., & Galderisi, U. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01921-2 · Cited by 41 · see citing works
“…the release of several factors, collectively indicated as the senescence-associated secretory phenotype (SASP), which can induce senescence of healthy cells (secondary senescence), modulate the immune system function, reshape the extracellular matrix, and facilitate cancer advancement [5–7].”
Xue, H., Zhao, B., Towers, M., Liao, L., Luzete-Monteiro, E., Xu, X., Freeman, C., Peng, H., Tang, H., Havas, A. P., et al. (2024) · Nature Aging · doi:10.1038/s43587-023-00564-1 · Cited by 42 · see citing works
“A defining characteristic of senescent cells is the secretion of factors collectively termed the senescence-associated secretory phenotype (SASP), comprising proinflammatory cytokines, chemokines, growth factors and other components 1,2 .”
Self-citationPeng, K., Yao, Y.-X., Lu, X., Wang, W.-J., Zhang, Y., Zhao, H., Wang, H., Xu, D., & Tan, Z.-X. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.135103 · Cited by 39 · see citing works
Pro‐inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis
Shang, D., Liu, H., & Tu, Z. (2023) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12915 · Cited by 37 · see citing works
Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics
Wang, Y., Zhang, H., & Miao, C. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07714-w · Cited by 41 · see citing works
“The SASP de fi nes the capacity of senescent cells, including immune cells and non-immune cells, to secret a variety of extracellular modulators, such as in fl ammatory cytokines, chemokines and growth factors [16].”
Zhao, S., Qiao, Z., Pfeifer, R., Pape, H.-C., Mao, K., Tang, H., Meng, B., Chen, S., & Liu, H. (2024) · European Journal of Medical Research · doi:10.1186/s40001-023-01604-7 · Cited by 35 · see citing works
“…however, based on the different modes of action of SASP activity, SASP can be classified into three types, receptor-requiring (IL-1, IL-1β, IL-6, IL-8, CXCL-1, CXCL-3, CXCL-10, HGF, TGF-β, GM-CSF, etc.); direct-response (MMPs, ROS, etc.); and regulatory (TIMPs, IGFBPs, etc) [10, 12, 14, 16–18].”
BackgroundTitration of RAS alters senescent state and influences tumour initiation
Chan, A. S. L., Zhu, H., Narita, M., Cassidy, L. D., Young, A. R. J., Bermejo‐Rodríguez, C., Janowska, A. T., Chen, H., Gough, S., Oshimori, N., et al. (2024) · Nature · doi:10.1038/s41586-024-07797-z · Cited by 34 · see citing works
Joshi, C. S., Salazar, A., Wang, C., Ligon, M. M., Chappidi, R. R., Fashemi, B., Felder, P. A., Mora, A., Grimm, S. L., Coarfa, C., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.11.017 · Cited by 33 · see citing works
Self-citationGiorgio, E. D., Ranzino, L., Tolotto, V., Dalla, E., Burelli, M., Gualandi, N., & Brancolini, C. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06548-2 · Cited by 32 · see citing works
“However, as SASP is not only involved in enhancing senescence but has other effects [57 – 59], ERVs activation might also in fl uence other aspects of SASP.”
Senescence of Hepatic Stellate Cells by Specific Delivery of Manganese for Limiting Liver Fibrosis
Gu, L., Zhao, C., Wang, Y., Wang, C., Yin, X., Ye, Q., Liu, Y., Zou, X., Wang, L., Zhuge, Y., et al. (2024) · Nano Letters · doi:10.1021/acs.nanolett.3c03689 · Cited by 32 · see citing works
Self-citationAlessio, N., Acar, M. B., Squillaro, T., Aprile, D., Ayaz‐Güner, Ş., Bernardo, G. D., Peluso, G., Özcan, S., & Galderisi, U. (2023) · Cell Proliferation · doi:10.1111/cpr.13401 · Cited by 30 · see citing works
Yin, Z., Tian, L., Kou, W., Cao, G., Wang, L., Xia, Y.-F., Lin, Y., Tang, S., Zhang, J., & Yang, H. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156213 · Cited by 27 · see citing works
Hu, H., Wang, Q., Yu, D., Tao, X., Guo, M., Tian, S., Zhang, Q., Xu, M., Geng, X., Zhang, H., et al. (2024) · Advanced Science · doi:10.1002/advs.202413122 · Cited by 26 · see citing works
Sutanto, H., Fetarayani, D., Narendra, M. R., & Nasution, S. A. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.106488 · Cited by 30 · see citing works
“Additionally, mechanistic target of rapamycin (mTOR) and GATA4 pathways have been implicated in modulating the intensity and composition of SASP (Figure 1) [15,34,35].”
Zhang, M., Zhong, J., Song, Z., Xu, Q., Chen, Y., & Zhang, Z. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117068 · Cited by 24 · see citing works
Dasgupta, N., Lei, X., Shi, C. H., Arnold, R., Teneche, M. G., Miller, K. N., Rajesh, A., Davis, A. E. M., Anschau, V., Campos, A. R., et al. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.006 · Cited by 25 · see citing works
Remodeling of tumor microenvironment by cellular senescence and immunosenescence in cervical cancer
He, Y., Qiu, Y., Yang, X., Lu, G., & Zhao, S. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.11.002 · Cited by 25 · see citing works
Restructuring of Lamina-Associated Domains in Senescence and Cancer
Bellanger, A., Madsen‐Østerbye, J., Galigniana, N. M., & Collas, P. (2022) · Cells · doi:10.3390/cells11111846 · Cited by 23 · see citing works
NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype
Muela‐Zarzuela, I., Suarez-Rivero, J. M., Gallardo-Orihuela, A., Wang, C., Izawa, K., de Gregorio-Procopio, M., Couillin, I., Ryffel, B., Kitaura, J., Sanz, A., et al. (2024) · Inflammation Research · doi:10.1007/s00011-024-01892-7 · Cited by 28 · see citing works
“Recent studies demonstrate that chromatin is instrumental in regulating SASP and that stressed cells release extra-nuclear DNA, activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, thereby promoting inflammation [3].”
Self-citationResearch progress on interferon and cellular senescence
Wang, D., Chen, K., Wang, Z., Wu, H., & Li, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202400808rr · Cited by 23 · see citing works
“Taking IFN as an entry point, the study of the role and mechanism of IFN on cellular senescence is to delay cellular senescence and improve the healthy lifespan of the aging population (Figure 6).”
Wang, C., Tanizawa, H., Hill, C., Havas, A. P., Zhang, Q., Liao, L., Xue, H., Lei, X., Wang, L., Nie, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49745-5 · Cited by 20 · see citing works
Self-citationDeng, Y., Gao, H., & Wu, Q. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c07268 · Cited by 20 · see citing works
Breaking Cancer’s Momentum: CDK4/6 Inhibitors and the Promise of Combination Therapy
Liu, Y., Park, S., & Li, Y. (2025) · Cancers · doi:10.3390/cancers17121941 · Cited by 20 · see citing works
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2025) · Biogerontology · doi:10.1007/s10522-025-10353-5 · Cited by 19 · see citing works
Wang, P., Zhang, S., Liu, W., Lv, X., Wang, B., Hu, B., & Shao, Z. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111262 · Cited by 19 · see citing works
The senescence-associated secretory phenotype in ovarian cancer dissemination
Veenstra, J. P., Bittencourt, L. F. F., & Aird, K. M. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00049.2022 · Cited by 19 · see citing works
Mao, Z., Liú, W., Zou, R., Sun, L., Huang, S., Wu, L., Chen, L., Wu, J., Lu, S., Song, Z., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02157-3 · Cited by 18 · see citing works
Bisht, S., Mao, Y., & Easwaran, H. (2024) · Current Opinion in Oncology · doi:10.1097/cco.0000000000001020 · Cited by 17 · see citing works
“…appear follow a defined program, with formation of senescence-associated heterochromatic foci (SAHF) associated with heterochromatic markers such as histone H3K9 and K27 trimethylation (H3K9me3 and H3K27me3), the histone H2A variant mac-roH2A, and high mobility group A (HMGA) proteins [59– 61].”
BackgroundSalminen, A. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102926 · Cited by 15 · see citing works
Miyata, K., Zhou, X., Nishio, M., Hanyu, A., Chiba, M., Kawasaki, H., Osako, T., Takeuchi, K., Ohno, S., Ueno, T., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2305046120 · Cited by 13 · see citing works
“Recent studies by our group and others have suggested that changes in the higher-order structure of chromatin contribute to the development of SASP or SASP-like inflammatory gene expression (11, 19–22).”
Li, J., Wang, X., Nepovimová, E., Wu, Q., & Kuča, K. (2024) · Toxicology · doi:10.1016/j.tox.2024.153868 · Cited by 13 · see citing works
Zhu, J., Ao, X., Liu, Y., Zhou, S., Hou, Y., Yan, Z., Zhou, L., Chen, H., Wang, P., Liang, X., et al. (2024) · Respiratory Research · doi:10.1186/s12931-024-02914-y · Cited by 12 · see citing works
The role of high mobility group proteins in cellular senescence mechanisms
Chen, J., Li, H., Huang, Y., & Tang, Q. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1486281 · Cited by 12 · see citing works
“As a cytosolic DNA sensor, cGAS non-speci fi cally detects double-stranded DNA (dsDNA), playing a pivotal role in senescent cells and the formation of SASP (Hao et al., 2022; Takahashi et al., 2018).”
BackgroundInfluentialHu, R., Li, J., Huang, Q., Zhong, X., Sun, J., Yi, J., Peng, L., Liu, X., Yang, Y. H., Yang, W., et al. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118400 · Cited by 11 · see citing works
Liu, X., Li, Z., Zheng, Y., Wang, W., He, P., Guan, K., Wu, T., Wang, X., & Zhang, X. (2022) · Journal of Inflammation · doi:10.1186/s12950-022-00315-w · Cited by 11 · see citing works
Zhu, S., Zhang, Y., Li, C., Deng, Z., Yin, Y., Dong, Z., Kuang, L., Li, C., Hu, X., Yin, T., et al. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.01.022 · 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
Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells
Wang, X., Zhang, C., Su, J., Ren, S., Wang, X., Zhang, Y., Yuan, Z., He, X., Wu, X., Li, M., et al. (2024) · Aging and Disease · doi:10.14336/ad.2024.0579 · Cited by 9 · see citing works
“The SASP is a complex collection of inflammatory factors, chemotactic factors, and growth factors secreted by senescent cells [2, 52].”
Li, C., Wan, Y., Yang, J., Feng, C., Liu, J., Cao, Z. W., Li, C., Wang, P., Wang, X., & Zeng, Q. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135743 · Cited by 9 · see citing works
Physiological aging in three dimensions
Ma, F., & Sen, R. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.08.002 · Cited by 10 · see citing works
Tang, H., Gao, P., Peng, W., Wang, X., Wang, Z., Deng, W., Yin, K., & Zhu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01859-5 · Cited by 8 · see citing works
Multifaceted roles of cGAS-STING pathway in the lung cancer: from mechanisms to translation
Wei, M., Li, Q., Li, S., Wang, D., & Wang, Y. (2024) · PeerJ · doi:10.7717/peerj.18559 · 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
“Post-translational histone modifications play an important role in regulating transcriptional programs in senescent cells [60, 61], including in chemotherapy treated tumor cells [48], and could potentially maintain the state of cellular dormancy.”
Zhang, Y., Chu, J., Hou, Q., Qian, S., Wang, Z., Yang, Q., Song, W., Dong, L., Shi, Z., Gao, Y., et al. (2024) · International Journal of Oncology · doi:10.3892/ijo.2024.5653 · Cited by 6 · see citing works
“C motif chemokine ligand (CXCL)1], growth factors (granu‑ locyte‑macrophage colony‑stimulating factor) and matrix metalloprotein (matrix metalloproteinase 9), into the ageing environment and gradually induce a senescent‑associated secretory phenotype (SASP) (6,7).”
BackgroundAflatoxin B1 downregulates ARID3 genes to overcome senescence for inducing hepatocellular carcinoma
Ara, D., Dheeravath, S., & Mungamuri, S. K. (2024) · Toxicon · doi:10.1016/j.toxicon.2024.108114 · Cited by 6 · see citing works
Respiratory viral infections in the elderly: From the perspective of the aging immune system
Zhang, X., Xu, J., Wang, Y., Li, H., Yu, J., Shang, L., Shang, L., Hou, B., Zhang, X., & Cao, B. (2023) · The Innovation Medicine · doi:10.59717/j.xinn-med.2023.100022 · Cited by 6 · see citing works
NLRP1 inflammasome modulates senescence and senescence-associated secretory phenotypePreprint
Muela‐Zarzuela, I., Suarez-Rivero, J. M., Gallardo-Orihuela, A., Wan, C., Izawa, K., de Gregorio-Procopio, M., Coillin, I., Ryffel, B., Kitaura, J., Sanz, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.06.527254 · Cited by 6 · see citing works
“Recent studies demonstrates that chromatin is instrumental in regulating SASP and inflammation through the innate immune cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) which can be activated upon DNA sensing (3).”
BackgroundShahzaib, M., Aprile, D., Squillaro, T., Alessio, N., Peluso, G., Bernardo, G. D., & Galderisi, U. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102916 · Cited by 5 · see citing works
Yang, D., Guo, X., & Xi, R. (2025) · BioEssays · doi:10.1002/bies.70005 · Cited by 4 · see citing works
“Recent advancements in senolytics and senomorphics have opened new avenues for mitigating the detrimental effects of cell senescence [102, 103].”
Liao, Y., Dai, Y., Tang, Z., Ma, H., Tu, Z., Yuan, T., Li, Y., & Wang, B. (2025) · Materials & Design · doi:10.1016/j.matdes.2025.115142 · Cited by 4 · see citing works
Chen, B., Li, G., Fang, Q., Ding, P., & Gao, Y. (2026) · Inflammation and Regeneration · doi:10.1186/s41232-026-00416-6 · Cited by 5 · see citing works
“The SASP comprises a range of bioactive factors that can reinforce senescence in their source cells and influence both the local microenvironment and even the organism as a whole [9, 18].”
Duarte‐Olivenza, C., Moran, G., Hurlé, J. M., Lorda-Diez, C. I., & Montero, J. A. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06326-6 · Cited by 4 · see citing works
“Cell senescence is a defence mechanism of major importance in cancer, ageing, and degenerative diseases [45, 46].”
BackgroundEffect of cellular senescence on the response of human peritoneal mesothelial cells to TGF-β
Kawka, E., Herzog, R., Ruciński, M., Malińska, A., Unterwurzacher, M., Sacnun, J. M., Wagner, A., Kowalska, K., Jopek, K., Kucz-Chrostowska, A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-63250-1 · Cited by 5 · see citing works
Xue, H., Zhao, B., Yan, Q., Yano, M., Matsuoka, A., Qi, Y., Liao, L., Zielinski, R. J., Tang, H., Kossenkov, A. V., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01147-6 · Cited by 3 · see citing works
Self-citationLazarchuk, P., Nguyen, M. M., Curca, C., Pavlova, M. N., Oshima, J., & Sidorova, J. M. (2024) · Aging · doi:10.18632/aging.206132 · Cited by 3 · see citing works
“This, however, does not indicate a global heterochromatin dismantlement in RAF OIS [36–38], and indeed H3K9me3 is not reduced in OIS cells ([39], also see Figure 4B, left panel).”
BackgroundmiR-548az-5p induces amniotic epithelial cell senescence by regulating KATNAL1 expression in labor
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Chromatin Structure from Development to Ageing
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“59,60 Disruption of NF-κ B results in cellular senescence escape, presenting the low expression of IL-8 and IL-6.”
da Rosa, S. A., Oliveira, H. M., de Mendonça, L. B., de Oliveira, N. B., Jaeger, M. D. C., Pereira, L. C., Oliveira, F. D., Santos‐Sousa, D., Saez‐Calazans, F., Lenz, L. S., et al. (2026) · Aging Cell · doi:10.1111/acel.70477 · Cited by 3 · see citing works
“Considering the transcriptome, virtually all studies agree that senescent cells are heterogeneous with respect to levels of senescence markers (Tang et al. 2019; Neri et al. 2025), SASP constitution (Hernandez-Segura et al. 2017; Bitencourt et al. 2024), and survival pathways (Troiani et al. 2022).”
InfluentialMolecular mechanisms and recent advances in cellular senescence
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“These fragments have been identified as potent drivers of the cGAS-STING-SASP axis, and age-dependent down-regulation of their cognate nucleases further amplifies CCF accumulation, establishing a self-perpetuating vicious cycle [19, 156].”
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Cellular senescence and aging at the crossroad between immunity and cancer
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“5c) 11 .”
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cGAS–STING and DNA Damage Repair
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“Cellular senescence is characterized by stable cell-cycle arrest, metabolic alterations, and secretion of pro-in fl ammatory mediators collectively termed the senescence-associated secretory phenotype (SASP) (6, 7).”
Cheng, S., Zhao, Y., & Wang, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1982821
- Authors
- Hao, X., Wang, C., & Zhang, R.
- Affiliations
- The Wistar Institute (US)
- Corresponding author
- Zhang, Rugang
- Venue
- Trends in Cell Biology
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 32
- Issue
- 6
- Pages
- 513-526
- ISSN
- 0962-8924 (ISSN-L)
- PMC
- PMC9106822
- OpenAlex
- W4206396864
- Cited by
- 94
- References
- 95
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 41 · 2023: 15 · 2022: 4
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 345 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Trends in Cell Biology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (OC190181, OC180109)
- Ovarian Cancer Research Alliance (596552)
- Honorable Tina Brozman Foundation
- National Institutes of Health (R01CA163377, P01AG031862, R01CA243142, R01CA239128, R01CA160331, R01CA202919, P50CA228991, P30CA010815)
- 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 › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- senescence-associated secretory phenotype, cellular senescence, chromatin regulation, cGAS-STING pathway, innate immunity, transcriptional regulation, cancer, healthy aging, senolytics
- MeSH terms
- Senescence-Associated Secretory Phenotype, Chromatin, Cytoplasm, Humans, Neoplasms, Phenotype, Cellular Senescence
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