{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:59:10Z","timestamp":1787320750838,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"INSTITUTO DE SALUD CARLOS III, MINISTERIO DE CIENCIA, INNOVACI\u00d3N Y UNIVERSIDADES and FEDER funds","doi-asserted-by":"publisher","award":["P19\/01524"],"award-info":[{"award-number":["P19\/01524"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Presbycusis or Age-related hearing loss (ARHL) is a sensorineural hearing loss that affects communication, leading to depression and social isolation. Currently, there are no effective treatments against ARHL. It is known that cocoa products have high levels of polyphenol content (mainly flavonoids), that are potent anti-inflammatory and antioxidant agents with proven benefits for health. The objective is to determine the protective effect of cocoa at the cellular and molecular levels in Presbycusis. For in vitro study, we used House Ear Institute-Organ of Corti 1 (HEI-OC1), stria vascularis (SV-k1), and organ of Corti (OC-k3) cells (derived from the auditory organ of a transgenic mouse). Each cell line was divided into a control group (CTR) and an H2O2 group (induction of senescence by an oxygen radical). Additionally, every group of every cell line was treated with the cocoa polyphenolic extract (CPE), measuring different markers of apoptosis, viability, the activity of antioxidant enzymes, and oxidative\/nitrosative stress. The data show an increase of reactive oxidative and nitrogen species (ROS and RNS, respectively) in senescent cells compared to control ones. CPE treatment effectively reduced these high levels and correlated with a significant reduction in apoptosis cells by inhibiting the mitochondrial-apoptotic pathway. Furthermore, in senescence cells, the activity of antioxidant enzymes (Superoxide dismutase, SOD; Catalase, CAT; and Glutathione peroxidase, GPx) was recovered after CPE treatment. Administration of CPE also decreased oxidative DNA damage in the auditory senescent cells. In conclusion, CPE inhibits the activation of senescence-related apoptotic signaling by decreasing oxidative stress in auditory senescent cells.<\/jats:p>","DOI":"10.3390\/antiox11081450","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T22:03:42Z","timestamp":1658873022000},"page":"1450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Preventive Effect of Cocoa Flavonoids via Suppression of Oxidative Stress-Induced Apoptosis in Auditory Senescent Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Luz","family":"del Mar Rivas-Chac\u00f3n","sequence":"first","affiliation":[{"name":"Department Clinical Analysis, Hospital Universitario de Getafe, Carretera de Toledo, Km 12.5, 28905 Getafe, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Yanes-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department Otolaryngology, Hospital Universitario de Getafe, Carretera de Toledo, Km 12.5, 28905 Getafe, Madrid, Spain"},{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"de Lucas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-2711","authenticated-orcid":false,"given":"Juan Ignacio","family":"Riestra-Ayora","sequence":"additional","affiliation":[{"name":"Department Otolaryngology, Hospital Universitario de Getafe, Carretera de Toledo, Km 12.5, 28905 Getafe, Madrid, Spain"},{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4094-261X","authenticated-orcid":false,"given":"Raquel","family":"Madrid-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Sanz-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department Otolaryngology, Hospital Universitario de Getafe, Carretera de Toledo, Km 12.5, 28905 Getafe, Madrid, Spain"},{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-0449","authenticated-orcid":false,"given":"Carolina","family":"S\u00e1nchez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.neuroscience.2014.11.061","article-title":"NADPH oxidase 2-dependent oxidative stress, mitochondrial damage and apoptosis in the ventral cochlear nucleus of D-gal aging rats","volume":"286","author":"Du","year":"2015","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1007\/s00405-016-4378-6","article-title":"Role of antioxidants in prevention of age-related hearing loss: A review of literatura","volume":"274","author":"Tavanai","year":"2017","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_3","unstructured":"World Health Organization (2018). Addressing the Rising Prevalence of Hearing Loss, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.exger.2010.12.003","article-title":"Pathogenesis of presbycusis in animal models: A review","volume":"46","author":"Fetoni","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.heares.2013.01.021","article-title":"Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways","volume":"303","author":"Yamasoba","year":"2013","journal-title":"Hear Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, J., and Puel, J.L. (2020). Presbycusis: An Update on Cochlear Mechanisms and Therapies. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010218"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10522-013-9475-y","article-title":"The role of mitochondria in age-related hearing loss","volume":"15","author":"Chen","year":"2014","journal-title":"Biogerontology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"582849","DOI":"10.1155\/2014\/582849","article-title":"Oxidative Stresses and mitochondrial dysfunction in age-related hearing loss","volume":"2014","author":"Fujimoto","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/00129492-200407000-00035","article-title":"Caspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells","volume":"25","author":"Lallemend","year":"2004","journal-title":"Otol. Neurotol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.neuint.2018.12.008","article-title":"NADPH oxidase inhibitor apocynin decreases mitochondrial dysfunction and apoptosis in the ventral cochlear nucleus of D-galactose-induced aging model in rats","volume":"124","author":"Du","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.otohns.2010.03.024","article-title":"Antioxidant enzymes, presbycusis, and ethnic variability","volume":"143","author":"Bared","year":"2010","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1039\/C8FO01997E","article-title":"The effects of polyphenols and other bioactives on human health","volume":"10","author":"Fraga","year":"2019","journal-title":"Food Funct."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.foodchem.2018.06.152","article-title":"Polyphenols in carobs: A review on their composition, antioxidant capacity and cytotoxic effects, and health impact","volume":"269","author":"Stavrou","year":"2018","journal-title":"Food Chem."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Serino, A., and Salazar, G. (2018). Protective Role of Polyphenols against Vascular Inflammation, Aging and Cardiovascular Disease. Nutrients, 11.","DOI":"10.3390\/nu11010053"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408398.2012.657921","article-title":"Cocoa and Human Health: From Head to Foot\u2014A Review","volume":"56","author":"Gattward","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"891","DOI":"10.2174\/1389201016666150610160652","article-title":"Anti-Oxidative Polyphenolic Compounds of Cocoa","volume":"16","author":"Nabavi","year":"2015","journal-title":"Curr. Pharm Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00405-015-3551-7","article-title":"Accuracy of auditory steady state and auditory brainstem responses to detect the preventive effect of polyphenols on age-related hearing loss in Sprague\u2013Dawley rats","volume":"273","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.exger.2016.07.005","article-title":"Protective effect of polyphenols on presbycusis via oxidative\/nitrosative stress suppression in rats","volume":"83","author":"Cuadrado","year":"2016","journal-title":"Exp. Gerontol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10522-018-9747-7","article-title":"Polyphenols protect against age-associated apoptosis in female rat cochleae","volume":"19","author":"Cuadrado","year":"2018","journal-title":"Biogerontology"},{"key":"ref_20","first-page":"e54425","article-title":"Working with Auditory HEI-OC1 Cells","volume":"115","author":"Kalinec","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jnutbio.2008.10.009","article-title":"Cocoa flavonoids up-regulate antioxidant enzyme activity via the ERK1\/2 pathway to protect against oxidative stress-induced apoptosis in HepG2 cells","volume":"21","author":"Ramos","year":"2010","journal-title":"J. Nutr. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.5344\/ajev.1998.49.2.135","article-title":"Characterization of the dietary fiber and the in vitro indigestible fraction of grape pomace","volume":"49","author":"Bravo","year":"1998","journal-title":"Am. J. Enol. Vitic."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rivas-Chac\u00f3n, L.D.M., Mart\u00ednez-Rodr\u00edguez, S., Madrid-Garc\u00eda, R., Yanes-D\u00edaz, J., Riestra-Ayora, J.I., Sanz-Fern\u00e1ndez, R., and S\u00e1nchez-Rodr\u00edguez, C. (2021). Role of Oxidative Stress in the Senescence Pattern of Auditory Cells in Age-Related Hearing Loss. Antioxidants, 10.","DOI":"10.3390\/antiox10091497"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.freeradbiomed.2007.06.026","article-title":"Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects","volume":"43","author":"Wardman","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2011.09.030","article-title":"Measuring reactive oxygen and nitrogen species with fluorescent probes: Challenges and limitations","volume":"52","author":"Kalyanaramana","year":"2012","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/sj.bjp.0707405","article-title":"The anticancer drug cisplatin induces an intrinsic apoptotic pathway inside the inner ear","volume":"152","author":"Nevado","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tan, T.Y.C., Lim, X.Y., Yeo, J.H.H., Lee, S.W.H., and Lai, N.M. (2021). The Health Effects of Chocolate and Cocoa: A Systematic Review. Nutrients, 13.","DOI":"10.3390\/nu13092909"},{"key":"ref_28","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 MAPK\u03b1 dependent manner","volume":"46","author":"Luo","year":"2012","journal-title":"Exp. Gerontol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.7150\/ijms.27181","article-title":"Comparison of Oxidative Stress Effects on Senescence Patterning of Human Adult and Perinatal Tissue-Derived Stem Cells in Short and Long-term Cultures","volume":"20","author":"Facchin","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.18632\/oncotarget.2874","article-title":"Autophagy through 4EBP1 and AMPK regulates oxidative stress-induced premature senescence in auditory cells","volume":"6","author":"Tsuchihashi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3389\/fncel.2019.00550","article-title":"Inhibition of DRP-1-Dependent Mitophagy Promotes Cochlea Hair Cell Senescence and Exacerbates Age-Related Hearing Loss","volume":"13","author":"Lin","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/BF02114761","article-title":"Appearance of free radicals in the guinea pig inner ear after noise-induced acoustic trauma","volume":"252","author":"Yamane","year":"1995","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.neuroscience.2009.02.085","article-title":"Generation of highly-reactive oxygen species is closely related to hair cell damage in rat organ of corti treated with gentamicin","volume":"161","author":"Choung","year":"2009","journal-title":"Neuroscience"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic. Bio. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.fct.2011.11.052","article-title":"A polyphenol-enriched cocoa extract reduces free radicals produced by mycotoxins","volume":"50","author":"Corcuera","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.jnutbio.2010.10.005","article-title":"Procyanidin B2 and a cocoa polyphenolic extract inhibit acrylamide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway","volume":"22","author":"Ramos","year":"2011","journal-title":"J. Nutr. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s00394-008-0761-4","article-title":"Neuroprotective effect of cocoa flavonids on in vitro oxidative stress","volume":"48","author":"Lee","year":"2009","journal-title":"Eur. J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.freeradbiomed.2009.02.010","article-title":"Cocoa procyanidins attenuate 4-hydroxynonenalinduced apoptosis of PC12 cells by directly inhibiting mitogenactivated protein kinase kinase 4 activity","volume":"46","author":"Cho","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mrfmmm.2007.12.012","article-title":"Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK","volume":"640","author":"Cho","year":"2008","journal-title":"Mut. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell. Physiol Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1080\/10408398.2018.1546669","article-title":"Bioactivity of dietary polyphenols: The role of metabolites","volume":"60","author":"Luca","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7765","DOI":"10.1021\/jf801744r","article-title":"Protection of human HepG2 cells against oxidative stress by cocoa phenolic extract","volume":"56","author":"Martin","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.3390\/nu5082955","article-title":"Cocoa phenolic extract protects pancreatic beta cells against oxidative stress","volume":"5","author":"Ramos","year":"2013","journal-title":"Nutrients"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/mnfr.201400492","article-title":"Cocoa flavonoids protect hepatic cells function against high glucose induced oxidative stress. Relevance of MAPKs","volume":"59","author":"Cordero","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1142\/S0192415X0900720X","article-title":"Protective effect of ursolic acid from Cornus officinalis on the hydrogen peroxide-induced damage of HEI-OC1 auditory cells","volume":"37","author":"Yu","year":"2009","journal-title":"Am. J. Chin. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.phrs.2012.05.009","article-title":"Cocoa intake attenuates oxidative stress associated with rat adjuvant arthritis","volume":"66","author":"Franch","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_47","first-page":"39","article-title":"Cocoa powder extracts exhibits hypolipidemic potential in cholesterol-fed rats","volume":"41","author":"Nwichi","year":"2012","journal-title":"Afr. J. Med. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1093\/jn\/133.9.2812","article-title":"Total Antioxidant Capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays","volume":"133","author":"Pellegrini","year":"2003","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/4241013a","article-title":"Plasma antioxidants from chocolate","volume":"424","author":"Serafini","year":"2003","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1093\/jn\/137.6.1436","article-title":"Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo and hypercholesterolemic humans after intake of different levels of cocoa powder","volume":"137","author":"Baba","year":"2007","journal-title":"J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1179\/135100004225004814","article-title":"Understanding the association between dietary antioxidants, redox status and disease: Is the Total Antioxidant Capacity the right tool?","volume":"9","author":"Serafini","year":"2004","journal-title":"Redox Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.exger.2006.10.014","article-title":"Age-related hearing loss in CD\/1 mice is associated to ROS formation and HIF target proteins up-regulation in the cochlea","volume":"42","author":"Riva","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13275","DOI":"10.1111\/acel.13275","article-title":"G6PD overexpression protects from oxidative stress and age-related hearing loss","volume":"19","author":"Celaya","year":"2020","journal-title":"Aging Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-94-007-2869-1_7","article-title":"The mitochondrial pathways of apoptosis","volume":"942","author":"Estaquier","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kim, S.J., Lee, J.H., Kim, B.S., So, H.S., Park, R., Myung, N.Y., Um, J.Y., and Hong, S.H. (2012). (-)-Epigallocatechin-3-gallate protects against NO-induced ototoxicity through the regulation of caspase- 1, caspase-3, and NF-\u03baB activation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043967"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mito.2013.10.007","article-title":"A short review on the implications of base excision repair pathway for neurons: Relevance to neurodegenerative diseases","volume":"16","author":"Mantha","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0891-5849(94)00209-3","article-title":"Reactions of oxyl radicals with DNA","volume":"18","author":"Breen","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5950","DOI":"10.1007\/s12035-019-1493-6","article-title":"ROS-Induced Activation of DNA Damage Responses Drives Senescence-Like State in Postmitotic Cochlear Cells: Implication for Hearing Preservation","volume":"56","author":"Benkafadar","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11357-011-9229-1","article-title":"Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects","volume":"34","author":"Camargo","year":"2012","journal-title":"Age"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:56:53Z","timestamp":1760140613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,26]]},"references-count":59,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["antiox11081450"],"URL":"https:\/\/doi.org\/10.3390\/antiox11081450","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,26]]}}}