{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:45:06Z","timestamp":1782697506194,"version":"3.54.5"},"reference-count":196,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Autophagy was originally identified as a survival mechanism to allow cells to survive under nutrient-deprived or stressful conditions whereas cellular senescence was considered a tumor-suppressive mechanism. Both processes can be induced by similar stimuli and can influence each other. There have been continued debates about whether they are causally linked, whether autophagy promotes or prevents senescence or if they are independent of each other. Protein kinases play integral roles in cell fate decision and have a major influence on both autophagy and senescence. While mechanistic target of rapamycin complex 1 is considered the master regulator of autophagy, it also influences senescence. Mitogen-activated protein kinases originally associated with senescence can regulate autophagy. While there have been numerous review articles on the interplay between autophagy and senescence, a comprehensive review on how various kinases participate in this interplay is lacking. The purpose of this review is to learn lessons from some old and recent studies to understand how kinases contribute to this changing field. Since both autophagy and senescence can have beneficial and detrimental effects and kinases are important drug targets, insights regarding how kinases orchestrate these two processes should help develop therapeutic strategies to treat diseases, such as aging and cancer.<\/jats:p>","DOI":"10.3390\/cells15131176","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Orchestration of Autophagy and Senescence: Kinases Take the Center Stage"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-0788","authenticated-orcid":false,"given":"Alakananda","family":"Basu","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gomez-Virgilio, L., Silva-Lucero, M.D., Flores-Morelos, D.S., Gallardo-Nieto, J., Lopez-Toledo, G., Abarca-Fernandez, A.M., Zacapala-Gomez, A.E., Luna-Munoz, J., Montiel-Sosa, F., and Soto-Rojas, L.O. (2022). Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators. Cells, 11.","DOI":"10.3390\/cells11152262"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41576-022-00562-w","article-title":"Autophagy genes in biology and disease","volume":"24","author":"Yamamoto","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.ccell.2025.05.015","article-title":"Senescence in cancer","volume":"43","author":"Colucci","year":"2025","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-pathol-020712-163918","article-title":"Autophagy as a stress-response and quality-control mechanism: Implications for cell injury and human disease","volume":"8","author":"Murrow","year":"2013","journal-title":"Annu. Rev. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"166262","DOI":"10.1016\/j.bbadis.2021.166262","article-title":"A perspective on the role of autophagy in cancer","volume":"1867","author":"Ariosa","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1002\/1878-0261.13269","article-title":"Autophagy at the intersection of aging, senescence, and cancer","volume":"16","author":"Cassidy","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp. Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/geront\/4.4.195","article-title":"The Immunologic Theory of Aging","volume":"4","author":"Walford","year":"1964","journal-title":"Gerontologist"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"116277","DOI":"10.1016\/j.bcp.2024.116277","article-title":"Risk factors of using late-autophagy inhibitors: Aspects to consider when combined with anticancer therapies","volume":"225","author":"Skrzeszewski","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e70048","DOI":"10.1002\/mco2.70048","article-title":"The crosstalk between senescence, tumor, and immunity: Molecular mechanism and therapeutic opportunities","volume":"6","author":"Wang","year":"2025","journal-title":"MedComm (2020)"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1101\/gad.519709","article-title":"Autophagy mediates the mitotic senescence transition","volume":"23","author":"Young","year":"2009","journal-title":"Genes Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/onc.2011.394","article-title":"AKT induces senescence in human cells via mTORC1 and p53 in the absence of DNA damage: Implications for targeting mTOR during malignancy","volume":"31","author":"Astle","year":"2012","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1172\/JCI40535","article-title":"A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis","volume":"120","author":"Alimonti","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/febs.16735","article-title":"Cellular senescence: Beneficial, harmful, and highly complex","volume":"290","author":"Baker","year":"2023","journal-title":"FEBS J."},{"key":"ref_15","first-page":"354","article-title":"Cellular senescence: A link between cancer and age-related degenerative disease?","volume":"21","author":"Campisi","year":"2011","journal-title":"Semin. Cancer Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41581-022-00601-z","article-title":"Cellular senescence: The good, the bad and the unknown","volume":"18","author":"Huang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1083\/jcb.201708092","article-title":"Senescence and aging: Causes, consequences, and therapeutic avenues","volume":"217","author":"McHugh","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603980","DOI":"10.1155\/2014\/603980","article-title":"Tumor suppression and promotion by autophagy","volume":"2014","author":"Avalos","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.molonc.2009.05.007","article-title":"Autophagy in tumour suppression and promotion","volume":"3","author":"Brech","year":"2009","journal-title":"Mol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chavez-Dominguez, R., Perez-Medina, M., Lopez-Gonzalez, J.S., Galicia-Velasco, M., and Aguilar-Cazares, D. (2020). The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.578418"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.devcel.2023.05.010","article-title":"Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies","volume":"58","author":"Gil","year":"2023","journal-title":"Dev. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.cell.2013.11.019","article-title":"Autophagy-mediated tumor promotion","volume":"155","author":"Guo","year":"2013","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"607","DOI":"10.14348\/molcells.2017.0151","article-title":"Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot","volume":"40","author":"Kwon","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s41556-023-01168-y","article-title":"Autophagy prevents microglial senescence","volume":"25","author":"Amin","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104079","DOI":"10.1016\/j.redox.2026.104079","article-title":"The autophagy-senescence axis as a threshold model of aging and therapeutic targeting","volume":"91","author":"Bahar","year":"2026","journal-title":"Redox Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"808","DOI":"10.4161\/auto.23922","article-title":"Autophagy and senescence: A partnership in search of definition","volume":"9","author":"Gewirtz","year":"2013","journal-title":"Autophagy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1080\/15548627.2015.1121361","article-title":"How autophagy both activates and inhibits cellular senescence","volume":"12","author":"Kang","year":"2016","journal-title":"Autophagy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.devcel.2021.04.008","article-title":"Coordinate regulation of the senescent state by selective autophagy","volume":"56","author":"Lee","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, Q., Lin, Y., Liang, G., Xiao, N., Zhang, H., Yang, X., Yang, J., and Liu, A. (2023). Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316880"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Masliah, E. (2025). Role of the Interplay Between Autophagy and Cell Senescence in the Pathogenesis and Therapeutics of Glioblastoma in the Aging Population. Cells, 14.","DOI":"10.3390\/cells14221764"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pantelis, P., Theocharous, G., Lagopati, N., Veroutis, D., Thanos, D.F., Lampoglou, G.P., Pippa, N., Gatou, M.A., Tremi, I., and Papaspyropoulos, A. (2023). The Dual Role of Oxidative-Stress-Induced Autophagy in Cellular Senescence: Comprehension and Therapeutic Approaches. Antioxidants, 12.","DOI":"10.3390\/antiox12010169"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"110544","DOI":"10.1016\/j.fct.2019.05.052","article-title":"Targeting pro-senescence mitogen activated protein kinase (Mapk) enzymes with bioactive natural compounds","volume":"131","author":"Cano","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cayo, A., Venturini, W., Rebolledo-Mira, D., Moore-Carrasco, R., Herrada, A.A., Nova-Lamperti, E., Valenzuela, C., and Brown, N.E. (2023). Palbociclib-Induced Cellular Senescence Is Modulated by the mTOR Complex 1 and Autophagy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119284"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, L., Zhang, G., Yang, Z., and Kang, X. (2024). Stress-Activated Protein Kinases in Intervertebral Disc Degeneration: Unraveling the Impact of JNK and p38 MAPK. Biomolecules, 14.","DOI":"10.3390\/biom14040393"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/bs.acr.2021.02.002","article-title":"mTOR as a senescence manipulation target: A forked road","volume":"150","author":"Saoudaoui","year":"2021","journal-title":"Adv. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41419-026-08496-5","article-title":"mTOR-driven autophagy suppression defines metabolic vulnerability in CDK4\/6 inhibitor-resistant HR+\/HER2\u2212 breast cancer","volume":"17","author":"Stroh","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"He","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: Navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Sridharan, S., and Basu, A. (2020). Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041199"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BST0370217","article-title":"A complex interplay between Akt, TSC2 and the two mTOR complexes","volume":"37","author":"Huang","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrc1974","article-title":"mTOR and cancer: Insights into a complex relationship","volume":"6","author":"Sabatini","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: Guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0092-8674(03)00929-2","article-title":"TSC2 mediates cellular energy response to control cell growth and survival","volume":"115","author":"Inoki","year":"2003","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.molcel.2005.03.027","article-title":"AMP-activated protein kinase induces a p53-dependent metabolic checkpoint","volume":"18","author":"Jones","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-024-02080-z","article-title":"Cyclin-dependent protein kinases and cell cycle regulation in biology and disease","volume":"10","author":"Pellarin","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41580-018-0003-4","article-title":"Mechanism and medical implications of mammalian autophagy","volume":"19","author":"Dikic","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1074\/jbc.R117.810366","article-title":"A molecular perspective of mammalian autophagosome biogenesis","volume":"293","author":"Mercer","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.4161\/auto.23323","article-title":"The ULK1 complex: Sensing nutrient signals for autophagy activation","volume":"9","author":"Wong","year":"2013","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10940","DOI":"10.1038\/s41598-020-67780-2","article-title":"ULK1 and ULK2 are less redundant than previously thought: Computational analysis uncovers distinct regulation and functions of these autophagy induction proteins","volume":"10","author":"Demeter","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/MCB.06159-11","article-title":"Role of AMPK-mTOR-Ulk1\/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks","volume":"32","author":"Alers","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dossou, A.S., and Basu, A. (2019). The Emerging Roles of mTORC1 in Macromanaging Autophagy. Cancers, 11.","DOI":"10.3390\/cancers11101422"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17803","DOI":"10.1038\/s41598-020-75030-8","article-title":"Fine-tuning of AMPK-ULK1-mTORC1 regulatory triangle is crucial for autophagy oscillation","volume":"10","author":"Holczer","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/s41467-023-38401-z","article-title":"Redefining the role of AMPK in autophagy and the energy stress response","volume":"14","author":"Park","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1042\/EBC20170021","article-title":"The mammalian ULK1 complex and autophagy initiation","volume":"61","author":"Zachari","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.molcel.2019.10.016","article-title":"An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis","volume":"77","author":"Odle","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/15548627.2016.1140293","article-title":"The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14","volume":"12","author":"Park","year":"2016","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/ncb2757","article-title":"ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase","volume":"15","author":"Russell","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.4161\/cc.25835","article-title":"mTOR, AMBRA1, and autophagy: An intricate relationship","volume":"12","author":"Nazio","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.molcel.2010.05.009","article-title":"Negative regulation of Vps34 by Cdk mediated phosphorylation","volume":"38","author":"Furuya","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.freeradbiomed.2011.06.016","article-title":"Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation","volume":"51","author":"Xie","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21412","DOI":"10.1074\/jbc.M109.026013","article-title":"A non-canonical MEK\/ERK signaling pathway regulates autophagy via regulating Beclin 1","volume":"284","author":"Wang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"169288","DOI":"10.1016\/j.jmb.2025.169288","article-title":"ATG9 Not Just an Autophagy Related Protein","volume":"437","author":"Millard","year":"2025","journal-title":"J. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/s41594-020-00518-w","article-title":"Atg9 is a lipid scramblase that mediates autophagosomal membrane expansion","volume":"27","author":"Matoba","year":"2020","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3888","DOI":"10.1242\/jcs.03172","article-title":"Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes","volume":"119","author":"Young","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/cr.2016.146","article-title":"Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy","volume":"27","author":"Zhou","year":"2017","journal-title":"Cell Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4379","DOI":"10.1128\/MCB.00740-14","article-title":"Metabolic-stress-induced rearrangement of the 14-3-3zeta interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3zeta interaction with phosphorylated Atg9","volume":"34","author":"Weerasekara","year":"2014","journal-title":"Mol. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/emboj.2009.321","article-title":"Coordinated regulation of autophagy by p38alpha MAPK through mAtg9 and p38IP","volume":"29","author":"Webber","year":"2010","journal-title":"EMBO J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/ncb1740","article-title":"Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking","volume":"10","author":"Liang","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Barnaba, C., Broadbent, D.G., Perez, G.I., and Schmidt, J.C. (2023). AMPK Regulates Phagophore-to-Autophagosome Maturation. bioRxiv.","DOI":"10.1101\/2023.09.28.559981"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1440-1711.2006.01454.x","article-title":"Insulin-like growth factor-1 and TNF-alpha regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells","volume":"84","author":"Jia","year":"2006","journal-title":"Immunol. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1479-5876-9-161","article-title":"c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells","volume":"9","author":"Sun","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Park, N.Y., Jo, D.S., and Cho, D.H. (2022). Post-Translational Modifications of ATG4B in the Regulation of Autophagy. Cells, 11.","DOI":"10.3390\/cells11081330"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/cdd.2012.129","article-title":"Phosphorylation of Atg5 by the Gadd45beta-MEKK4-p38 pathway inhibits autophagy","volume":"20","author":"Keil","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Wong, C.H., Iskandar, K.B., Yadav, S.K., Hirpara, J.L., Loh, T., and Pervaiz, S. (2016). Correction: Simultaneous Induction of Non-Canonical Autophagy and Apoptosis in Cancer Cells by ROS-Dependent ERK and JNK Activation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159352"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e46885","DOI":"10.15252\/embr.201846885","article-title":"ULK1-mediated phosphorylation of ATG16L1 promotes xenophagy, but destabilizes the ATG16L1 Crohn\u2019s mutant","volume":"20","author":"Alsaadi","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.molcel.2014.11.013","article-title":"mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation","volume":"57","author":"Kim","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.15252\/embj.201590992","article-title":"mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival","volume":"34","author":"Munson","year":"2015","journal-title":"EMBO J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1038\/s41418-022-01028-6","article-title":"Past, present, and future perspectives of transcription factor EB (TFEB): Mechanisms of regulation and association with disease","volume":"29","author":"Tan","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1038\/s41467-018-05449-1","article-title":"Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.molcel.2011.06.018","article-title":"Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy","volume":"43","author":"Joo","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev-physiol-030212-183653","article-title":"Aging, cellular senescence, and cancer","volume":"75","author":"Campisi","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s11357-020-00183-3","article-title":"Regulation of senescence traits by MAPKs","volume":"42","author":"Anerillas","year":"2020","journal-title":"Geroscience"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.tcb.2021.01.010","article-title":"New Insights into CDK Regulators: Novel Opportunities for Cancer Therapy","volume":"31","author":"Bury","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s00204-023-03540-1","article-title":"c-Jun N-terminal kinase signaling in cellular senescence","volume":"97","author":"Deng","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ijc.70442","article-title":"Cyclin-dependent kinases as therapeutic targets in cancer: Recent advances, challenges, and opportunities","volume":"159","author":"Ju","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kumari, R., and Jat, P. (2021). Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645593"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1158\/1541-7786.MCR-13-0350","article-title":"The molecular balancing act of p16INK4a in cancer and aging","volume":"12","author":"LaPak","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Li, Y., You, L., Nepovimova, E., Adam, V., Heger, Z., Jomova, K., Valko, M., Wu, Q., and Kuca, K. (2024). c-Jun N-terminal kinase signaling in aging. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1453710"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1038\/s41388-020-1354-9","article-title":"Senescence as a therapeutically relevant response to CDK4\/6 inhibitors","volume":"39","author":"Wagner","year":"2020","journal-title":"Oncogene"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"111549","DOI":"10.1016\/j.cellsig.2024.111549","article-title":"Targeting p38 MAPK: A potential bridge between ER stress and age-related bone loss","volume":"127","author":"Yin","year":"2025","journal-title":"Cell Signal"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41580-021-00404-3","article-title":"Cell cycle control in cancer","volume":"23","author":"Matthews","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/jb\/mvae079","article-title":"Cellular senescence: Mechanisms and relevance to cancer and aging","volume":"177","author":"Yamauchi","year":"2025","journal-title":"J. Biochem."},{"key":"ref_96","first-page":"1001","article-title":"The MDM2-p53 interaction","volume":"1","author":"Moll","year":"2003","journal-title":"Mol. Cancer Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"188556","DOI":"10.1016\/j.bbcan.2021.188556","article-title":"Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting","volume":"1876","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.15252\/embr.201439245","article-title":"Senescence and apoptosis: Dueling or complementary cell fates?","volume":"15","author":"Childs","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: P53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/S0959-437X(99)00038-6","article-title":"The ARF\/p53 pathway","volume":"10","author":"Sherr","year":"2000","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1101\/gad.12.19.3008","article-title":"Premature senescence involving p53 and p16 is activated in response to constitutive MEK\/MAPK mitogenic signaling","volume":"12","author":"Lin","year":"1998","journal-title":"Genes Dev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1101\/gad.12.19.2997","article-title":"Senescence of human fibroblasts induced by oncogenic Raf","volume":"12","author":"Zhu","year":"1998","journal-title":"Genes Dev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"G736","DOI":"10.1152\/ajpgi.00453.2003","article-title":"Dual role of MEK\/ERK signaling in senescence and transformation of intestinal epithelial cells","volume":"286","author":"Boucher","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1101\/gad.203984.112","article-title":"Tumor suppressor activity of the ERK\/MAPK pathway by promoting selective protein degradation","volume":"27","author":"Bourdeau","year":"2013","journal-title":"Genes Dev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1016\/j.cellsig.2013.08.014","article-title":"Depletion of ERK2 but not ERK1 abrogates oncogenic Ras-induced senescence","volume":"25","author":"Shin","year":"2013","journal-title":"Cell Signal"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"114044","DOI":"10.1016\/j.celrep.2024.114044","article-title":"A senescence restriction point acting on chromatin integrates oncogenic signals","volume":"43","author":"Bourdeau","year":"2024","journal-title":"Cell Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"15759","DOI":"10.1073\/pnas.0707782104","article-title":"Suppression of p53-dependent senescence by the JNK signal transduction pathway","volume":"104","author":"Das","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/onc.2009.355","article-title":"Prevention of premature senescence requires JNK regulation of Bcl-2 and reactive oxygen species","volume":"29","author":"Lee","year":"2010","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1101\/gad.331272.119","article-title":"Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence","volume":"34","author":"Vizioli","year":"2020","journal-title":"Genes Dev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.cels.2023.06.005","article-title":"Biphasic JNK-Erk signaling separates the induction and maintenance of cell senescence after DNA damage induced by topoisomerase II inhibition","volume":"14","author":"Netterfield","year":"2023","journal-title":"Cell Syst."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1365-2443.2003.00620.x","article-title":"Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway","volume":"8","author":"Iwasa","year":"2003","journal-title":"Genes Cells"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/msb.2010.5","article-title":"Feedback between p21 and reactive oxygen production is necessary for cell senescence","volume":"6","author":"Passos","year":"2010","journal-title":"Mol. Syst. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1038\/emboj.2011.69","article-title":"p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype","volume":"30","author":"Freund","year":"2011","journal-title":"EMBO J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1158\/0008-5472.CAN-20-0108","article-title":"Cellular Senescence Promotes Skin Carcinogenesis through p38MAPK and p44\/42MAPK Signaling","volume":"80","author":"Alimirah","year":"2020","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.abb.2016.10.016","article-title":"Reciprocal regulation of acetyl-CoA carboxylase 1 and senescence in human fibroblasts involves oxidant mediated p38 MAPK activation","volume":"613","author":"Marmisolle","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/jb\/mvu040","article-title":"Molecular mechanisms for the p38-induced cellular senescence in normal human fibroblast","volume":"156","author":"Harada","year":"2014","journal-title":"J. Biochem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1038\/emboj.2011.492","article-title":"Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation","volume":"31","author":"Barascu","year":"2012","journal-title":"EMBO J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e2419196122","DOI":"10.1073\/pnas.2419196122","article-title":"The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts","volume":"122","author":"Haj","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1128\/MCB.00784-13","article-title":"Induction of p38delta expression plays an essential role in oncogenic ras-induced senescence","volume":"33","author":"Kwong","year":"2013","journal-title":"Mol. Cell Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0092-8674(00)81902-9","article-title":"Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a","volume":"88","author":"Serrano","year":"1997","journal-title":"Cell"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"112252","DOI":"10.1016\/j.celrep.2023.112252","article-title":"Multi-range ERK responses shape the proliferative trajectory of single cells following oncogene induction","volume":"42","author":"Chen","year":"2023","journal-title":"Cell Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"116226","DOI":"10.1016\/j.celrep.2025.116226","article-title":"Chemogenetic tuning reveals optimal MAPK signaling for cell-fate programming","volume":"44","author":"Atkinson","year":"2025","journal-title":"Cell Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"12046","DOI":"10.1073\/pnas.1209660109","article-title":"JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate","volume":"109","author":"Hubner","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ccr.2007.04.021","article-title":"Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN","volume":"11","author":"Vivanco","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10522-015-9610-z","article-title":"Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2","volume":"17","author":"Alimbetov","year":"2016","journal-title":"Biogerontology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"11237","DOI":"10.1074\/jbc.M808327200","article-title":"p38alpha and p38gamma mediate oncogenic ras-induced senescence through differential mechanisms","volume":"284","author":"Kwong","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.tibs.2014.04.004","article-title":"Emerging roles of the p38 MAPK and PI3K\/AKT\/mTOR pathways in oncogene-induced senescence","volume":"39","author":"Xu","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Kuk, M.U., Kim, D., Lee, Y.H., Yoon, J.H., Park, J.H., Lee, Y.J., So, B.H., Kim, M., Kwon, H.W., and Byun, Y. (2024). Synergistic ROS Reduction Through the Co-Inhibition of BRAF and p38 MAPK Ameliorates Senescence. Antioxidants, 13.","DOI":"10.3390\/antiox13121465"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nature03918","article-title":"Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis","volume":"436","author":"Chen","year":"2005","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/s41388-018-0521-8","article-title":"mTOR kinase leads to PTEN-loss-induced cellular senescence by phosphorylating p53","volume":"38","author":"Jung","year":"2019","journal-title":"Oncogene"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41556-021-00655-4","article-title":"Author Correction: MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation","volume":"23","author":"Laberge","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41556-024-01443-6","article-title":"Author Correction: mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype","volume":"26","author":"Herranz","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"724","DOI":"10.15252\/embj.201592862","article-title":"Mitochondria are required for pro-ageing features of the senescent phenotype","volume":"35","author":"Marques","year":"2016","journal-title":"EMBO J."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1101\/gad.284851.116","article-title":"A senescence secretory switch mediated by PI3K\/AKT\/mTOR activation controls chemoprotective endothelial secretory responses","volume":"30","author":"Bent","year":"2016","journal-title":"Genes Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1158\/0008-5472.CAN-25-1175","article-title":"Cortactin Suppresses mTOR-Dependent Senescence in Circulating Tumor Cells","volume":"86","author":"Hu","year":"2026","journal-title":"Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"27016","DOI":"10.1074\/jbc.M300318200","article-title":"Increased AMP:ATP ratio and AMP-activated protein kinase activity during cellular senescence linked to reduced HuR function","volume":"278","author":"Wang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/MCB.01868-08","article-title":"Mitochondrial dysfunction contributes to oncogene-induced senescence","volume":"29","author":"Moiseeva","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cmet.2015.11.011","article-title":"Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype","volume":"23","author":"Wiley","year":"2016","journal-title":"Cell Metab."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e23250","DOI":"10.1096\/fj.202301273RR","article-title":"Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling","volume":"37","author":"Liang","year":"2023","journal-title":"FASEB J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1101\/gad.17276711","article-title":"Control of the senescence-associated secretory phenotype by NF-kappaB promotes senescence and enhances chemosensitivity","volume":"25","author":"Chien","year":"2011","journal-title":"Genes Dev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41418-019-0384-8","article-title":"A functional genetic screen defines the AKT-induced senescence signaling network","volume":"27","author":"Chan","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41392-021-00817-8","article-title":"Circulating tumor cells: Biology and clinical significance","volume":"6","author":"Lin","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.canlet.2008.02.066","article-title":"Cortactin in tumor invasiveness","volume":"265","author":"Weaver","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1038\/s42255-024-01130-8","article-title":"Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence","volume":"6","author":"Carapeto","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1126\/science.1205407","article-title":"Spatial coupling of mTOR and autophagy augments secretory phenotypes","volume":"332","author":"Narita","year":"2011","journal-title":"Science"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.molcel.2011.02.020","article-title":"Activation of the PIK3CA\/AKT pathway suppresses senescence induced by an activated RAS oncogene to promote tumorigenesis","volume":"42","author":"Kennedy","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.4161\/auto.25879","article-title":"Prolonged autophagy by MTOR inhibitor leads radioresistant cancer cells into senescence","volume":"9","author":"Nam","year":"2013","journal-title":"Autophagy"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.4161\/auto.28772","article-title":"Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells","volume":"10","author":"Huang","year":"2014","journal-title":"Autophagy"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/15548627.2015.1009795","article-title":"Single-cell analysis challenges the connection between autophagy and senescence induced by DNA damage","volume":"11","author":"Thome","year":"2015","journal-title":"Autophagy"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Kang, H.T., Lee, K.B., Kim, S.Y., Choi, H.R., and Park, S.C. (2011). Autophagy impairment induces premature senescence in primary human fibroblasts. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023367"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/15548627.2016.1247143","article-title":"Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence","volume":"13","author":"Tai","year":"2017","journal-title":"Autophagy"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"119411","DOI":"10.1016\/j.bbamcr.2022.119411","article-title":"Sirt3 activates autophagy to prevent DOX-induced senescence by inactivating PI3K\/AKT\/mTOR pathway in A549 cells","volume":"1870","author":"Fan","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"114754","DOI":"10.1016\/j.yexcr.2025.114754","article-title":"SIRT1 rescues autophagic flux via PI3K\/AKT\/mTOR inactivation to suppress DOX-induced senescence in MCF-7 cells","volume":"452","author":"Wu","year":"2025","journal-title":"Exp. Cell Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nature16187","article-title":"Autophagy maintains stemness by preventing senescence","volume":"529","author":"Perdiguero","year":"2016","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1083\/jcb.201610113","article-title":"Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing","volume":"216","author":"Carroll","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1080\/15548627.2020.1713640","article-title":"Autophagy drives fibroblast senescence through MTORC2 regulation","volume":"16","author":"Bernard","year":"2020","journal-title":"Autophagy"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/s41418-023-01129-w","article-title":"A novel tumor suppressor encoded by a 1p36.3 lncRNA functions as a phosphoinositide-binding protein repressing AKT phosphorylation\/activation and promoting autophagy","volume":"30","author":"Li","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Dalle Pezze, P., Nelson, G., Otten, E.G., Korolchuk, V.I., Kirkwood, T.B., von Zglinicki, T., and Shanley, D.P. (2014). Dynamic modelling of pathways to cellular senescence reveals strategies for targeted interventions. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003728"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1080\/15548627.2025.2469315","article-title":"Autophagy regulates cellular senescence by mediating the degradation of CDKN1A\/p21 and CDKN2A\/p16 through SQSTM1\/p62-mediated selective autophagy in myxomatous mitral valve degeneration","volume":"21","author":"Tang","year":"2025","journal-title":"Autophagy"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1158\/2159-8290.CD-25-0525","article-title":"p53 Drives Lung Cancer Regression through a TSC2\/TFEB-dependent Senescence Program","volume":"16","author":"Wang","year":"2026","journal-title":"Cancer Discov."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Franco-Juarez, B., Coronel-Cruz, C., Hernandez-Ochoa, B., Gomez-Manzo, S., Cardenas-Rodriguez, N., Arreguin-Espinosa, R., Bandala, C., Canseco-Avila, L.M., and Ortega-Cuellar, D. (2022). TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator. Cells, 11.","DOI":"10.3390\/cells11193153"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.arr.2011.12.005","article-title":"AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network","volume":"11","author":"Salminen","year":"2012","journal-title":"Ageing Res. Rev."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.3390\/ijms13033563","article-title":"Autophagy in premature senescent cells is activated via AMPK pathway","volume":"13","author":"Guo","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.3892\/or.2016.4699","article-title":"Oncogene-mediated tumor transformation sensitizes cells to autophagy induction","volume":"35","author":"Gargini","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"21991","DOI":"10.18632\/oncotarget.7831","article-title":"Activation of hERG3 channel stimulates autophagy and promotes cellular senescence in melanoma","volume":"7","author":"Haar","year":"2016","journal-title":"Oncotarget"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1158\/1541-7786.MCR-18-0024","article-title":"Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence","volume":"16","author":"Jakhar","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/acel.12446","article-title":"AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD+ elevation","volume":"15","author":"Han","year":"2016","journal-title":"Aging Cell"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"8376","DOI":"10.1111\/jcmm.16797","article-title":"Metformin alleviates oxidative stress-induced senescence of human lens epithelial cells via AMPK activation and autophagic flux restoration","volume":"25","author":"Chen","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_169","first-page":"8","article-title":"Metformin protects lens epithelial cells against senescence in a naturally aged mouse model","volume":"8","author":"Chen","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.stemcr.2018.06.014","article-title":"The AMPK\/p27Kip1 Axis Regulates Autophagy\/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells","volume":"11","author":"White","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"McKay, L.K., and White, J.P. (2021). The AMPK\/p27Kip1 Pathway as a Novel Target to Promote Autophagy and Resilience in Aged Cells. Cells, 10.","DOI":"10.3390\/cells10061430"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1128\/MCB.00118-16","article-title":"AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550","volume":"36","author":"Joo","year":"2016","journal-title":"Mol. Cell Biol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"272","DOI":"10.5483\/BMBRep.2020.53.5.044","article-title":"Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells","volume":"53","author":"Jang","year":"2020","journal-title":"BMB Rep."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1080\/15548627.2022.2155794","article-title":"Autophagy inhibition signals through senescence to promote tumor suppression","volume":"19","author":"Peng","year":"2023","journal-title":"Autophagy"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s10020-024-00825-8","article-title":"AMPK activation eliminates senescent cells in diabetic wound by inducing NCOA4 mediated ferritinophagy","volume":"30","author":"Liu","year":"2024","journal-title":"Mol. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.18632\/aging.101325","article-title":"Targeted elimination of senescent Ras-transformed cells by suppression of MEK\/ERK pathway","volume":"9","author":"Kochetkova","year":"2017","journal-title":"Aging"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.18632\/aging.101686","article-title":"Suppression of mTORC1 activity in senescent Ras-transformed cells neither restores autophagy nor abrogates apoptotic death caused by inhibition of MEK\/ERK kinases","volume":"10","author":"Kochetkova","year":"2018","journal-title":"Aging"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41591-019-0368-8","article-title":"Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer","volume":"25","author":"Bryant","year":"2019","journal-title":"Nat. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13046-019-1226-8","article-title":"Inhibition of ERK1\/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis","volume":"38","author":"Yan","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.exger.2011.07.005","article-title":"Autophagy regulates ROS-induced cellular senescence via p21 in a p38 MAPKalpha dependent manner","volume":"46","author":"Luo","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"13013","DOI":"10.1038\/srep13013","article-title":"Rhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1\/2 activation","volume":"5","author":"Athamneh","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/s41419-019-1607-0","article-title":"Autophagy-induced senescence is regulated by p38alpha signaling","volume":"10","author":"Slobodnyuk","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1089\/rej.2022.0043","article-title":"Restoration of Lysosomal and Mitochondrial Function Through p38 Mitogen-Activated Protein Kinase Inhibition Ameliorates Senescence","volume":"25","author":"Park","year":"2022","journal-title":"Rejuvenation Res."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4004","DOI":"10.1172\/JCI75051","article-title":"p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells","volume":"124","author":"Henson","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12979-025-00526-8","article-title":"p38 mitogen-activated protein kinase drives senescence in CD4+ T lymphocytes and increases their pathological potential","volume":"22","author":"Fukada","year":"2025","journal-title":"Immun. Ageing"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"114973","DOI":"10.1016\/j.yexcr.2026.114973","article-title":"PEX5 integrates the p38 MAPK signaling pathway and taurine metabolism to regulate senescence in lung fibroblasts","volume":"458","author":"Zheng","year":"2026","journal-title":"Exp. Cell Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"716","DOI":"10.2174\/1389450120666181204165344","article-title":"Cyclin-Dependent Kinase 2 in Cellular Senescence and Cancer. A Structural and Functional Review","volume":"20","author":"Volkart","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.4161\/cc.20718","article-title":"Autophagy and senescence in cancer-associated fibroblasts metabolically supports tumor growth and metastasis via glycolysis and ketone production","volume":"11","author":"Capparelli","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.4161\/cc.21884","article-title":"CDK inhibitors (p16\/p19\/p21) induce senescence and autophagy in cancer-associated fibroblasts, \u201cfueling\u201d tumor growth via paracrine interactions, without an increase in neo-angiogenesis","volume":"11","author":"Capparelli","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1158\/0008-5472.CAN-15-2347","article-title":"A CDK4\/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence","volume":"76","author":"Acevedo","year":"2016","journal-title":"Cancer Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.1158\/0008-5472.CAN-11-4139","article-title":"Cyclin D1 activity regulates autophagy and senescence in the mammary epithelium","volume":"72","author":"Brown","year":"2012","journal-title":"Cancer Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"15916","DOI":"10.1038\/ncomms15916","article-title":"CDK4\/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers","volume":"8","author":"Vijayaraghavan","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"101266","DOI":"10.1016\/j.neo.2025.101266","article-title":"Dual CDK4\/6-PI3K\/mTOR inhibition reinforces cytostatic programs and tumor control in preclinical models of primary and metastatic osteosarcoma","volume":"72","author":"Barghi","year":"2026","journal-title":"Neoplasia"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.yexcr.2017.09.031","article-title":"Palbociclib-induced autophagy and senescence in gastric cancer cells","volume":"360","author":"Valenzuela","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.bjp.0703534","article-title":"The p38 MAP kinase inhibitor SB203580 enhances nuclear factor-kappa B transcriptional activity by a non-specific effect upon the ERK pathway","volume":"131","author":"Birkenkamp","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1074\/jbc.275.10.7395","article-title":"The pyridinyl imidazole inhibitor SB203580 blocks phosphoinositide-dependent protein kinase activity, protein kinase B phosphorylation, and retinoblastoma hyperphosphorylation in interleukin-2-stimulated T cells independently of p38 mitogen-activated protein kinase","volume":"275","author":"Lali","year":"2000","journal-title":"J. Biol. Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T01:06:42Z","timestamp":1782695202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/13\/1176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":196,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15131176"],"URL":"https:\/\/doi.org\/10.3390\/cells15131176","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]}}}