{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:30:03Z","timestamp":1793388603988,"version":"4.5.0"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z01-AG000297"],"award-info":[{"award-number":["Z01-AG000297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Senescent cells accumulate with aging and have been shown to contribute to age-associated diseases and organ dysfunction. Eliminating senescent cells with senolytic drugs has been shown to improve age phenotypes in mouse models and there is some initial evidence that it may improve the health of persons with chronic diseases. In this study, we employed WI-38 human fibroblasts rendered senescent by exposure to ionizing radiation (IR) to screen several plant extracts for their potential senolytic and\/or senomorphic activity. Of these, ginger extract (\n                    <jats:italic>Zingiber officinale Rosc<\/jats:italic>\n                    .) selectively caused the death of senescent cells without affecting proliferating cells. Among the major individual components of ginger extract, gingerenone A and 6-shogaol showed promising senolytic properties, with gingerenone A selectively eliminating senescent cells. Similar to the senolytic cocktail dasatinib and quercetin (D+Q), gingerenone A and 6-shogaol elicited an apoptotic program. Additionally, both D+Q and gingerenone A had a pronounced effect on suppressing the senescence-associated secretory phenotype (SASP). Gingerenone A selectively promotes the death of senescent cells with no effect on non-senescent cells and these characteristics strongly support the idea that this natural compound may have therapeutic benefit in diseases characterized by senescent cell accumulation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0266135","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T13:43:09Z","timestamp":1648561389000},"page":"e0266135","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":41,"title":["Identification of gingerenone A as a novel senolytic compound"],"prefix":"10.1371","volume":"17","author":[{"given":"Ruin","family":"Moaddel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Munk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Khadeer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotb","family":"Abdelmohsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Gorospe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"pone.0266135.ref001","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":"L Hayflick","year":"1961","journal-title":"Exp. Cell Res"},{"issue":"22","key":"pone.0266135.ref002","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1101\/gad.1971610","article-title":"The essence of senescence","volume":"24","author":"T Kuilman","year":"2010","journal-title":"Genes & development"},{"issue":"4","key":"pone.0266135.ref003","doi-asserted-by":"crossref","first-page":"402","DOI":"10.18632\/aging.100042","article-title":"MicroRNAs miR-146a\/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8","volume":"1","author":"D Bhaumik","year":"2009","journal-title":"Aging (Albany NY)."},{"key":"pone.0266135.ref004","doi-asserted-by":"crossref","first-page":"27743","DOI":"10.3402\/pba.v5.27743","article-title":"The emerging role of senescent cells in tissue homeostasis and pathophysiology","volume":"5","author":"K. Tominaga","year":"2015","journal-title":"Pathobiol Aging Age Relat Dis"},{"issue":"1","key":"pone.0266135.ref005","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":"D McHugh","year":"2018","journal-title":"J Cell Biol"},{"issue":"5","key":"pone.0266135.ref006","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/joim.13141","article-title":"Senolytic drugs: from discovery to translation","volume":"288","author":"JL Kirkland","year":"2020","journal-title":"J Intern Med"},{"issue":"7372","key":"pone.0266135.ref007","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"DJ Baker","year":"2011","journal-title":"Nature"},{"issue":"10","key":"pone.0266135.ref008","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrd.2017.116","article-title":"Senescent cells: an emerging target for diseases of ageing","volume":"16","author":"BG Childs","year":"2017","journal-title":"Nature reviews. Drug discovery"},{"issue":"3","key":"pone.0266135.ref009","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular senescence and the senescent secretory phenotype: therapeutic opportunities","volume":"123","author":"T Tchkonia","year":"2013","journal-title":"J Clin Invest"},{"issue":"3","key":"pone.0266135.ref010","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/acel.12445","article-title":"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors","volume":"15","author":"Y Zhu","year":"2016","journal-title":"Aging Cell"},{"issue":"3","key":"pone.0266135.ref011","doi-asserted-by":"crossref","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463.","volume":"9","author":"Y Zhu","year":"2017","journal-title":"Aging (Albany NY)."},{"issue":"8","key":"pone.0266135.ref012","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"M Xu","year":"2018","journal-title":"Nat Med"},{"key":"pone.0266135.ref013","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41514-018-0023-5","article-title":"Blocking negative effects of senescence in human skin fibroblasts with a plant extract.","volume":"4","author":"I L\u00e4mmermann","year":"2018","journal-title":"NPJ Aging and Mech. Dis"},{"key":"pone.0266135.ref014","doi-asserted-by":"crossref","first-page":"2694945","DOI":"10.1155\/2017\/2694945","article-title":"An Extract from the Plant Deschampsia antarctica Protects Fibroblasts from Senescence Induced by Hydrogen Peroxide","volume":"2017","author":"A Ortiz-Esp\u00edn","year":"2017","journal-title":"Oxid Med Cell Longev"},{"issue":"19","key":"pone.0266135.ref015","doi-asserted-by":"crossref","first-page":"7400","DOI":"10.1021\/ac201403y","article-title":"Synthesis and characterization of SIRT6 protein coated magnetic beads: identification of a novel inhibitor of SIRT6 deacetylase from medicinal plant extracts","volume":"83","author":"M Yasuda","year":"2011","journal-title":"Anal Chem"},{"issue":"11","key":"pone.0266135.ref016","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1021\/np400478c","article-title":"Identification of CB1\/CB2 Ligands from Zanthoxylum bungeanum","volume":"76","author":"KSS Dossou","year":"2013","journal-title":"J.Nat.Products"},{"issue":"10","key":"pone.0266135.ref017","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4103\/0973-7847.91102","article-title":"Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives","volume":"5","author":"S Beg","year":"2011","journal-title":"Pharmacogn. Rev"},{"issue":"Suppl. 1","key":"pone.0266135.ref018","first-page":"32","article-title":"A complex of three natural anti-inflammatory agents provides relief of osteoarthritis pain","volume":"20","author":"T Conrozier","year":"2014","journal-title":"Altern. Ther. Health Med"},{"issue":"4","key":"pone.0266135.ref019","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1078\/0944-7113-00117","article-title":"Anti-inflammatory and antioxidant activities of cat\u2019s claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content","volume":"9","author":"M Sandoval","year":"2002","journal-title":"Phytomedicine"},{"issue":"Suppl 1","key":"pone.0266135.ref020","first-page":"S36","article-title":"Anti-oxidative and anti-inflammatory effects of ginger in health and physical activity: review of current evidence","volume":"4","author":"NS Mashhadi","year":"2013","journal-title":"Int J Prev Med"},{"issue":"4","key":"pone.0266135.ref021","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.it.2015.02.009","article-title":"Senescence-associated inflammatory responses: aging and cancer perspectives","volume":"36","author":"A Lasry","year":"2015","journal-title":"Trends in Immunology"},{"issue":"10","key":"pone.0266135.ref022","article-title":"Gingerenone A, a polyphenol present in ginger, suppresses obesity and adipose tissue inflammation in high-fat diet-fed mice","volume":"61","author":"S Suk","year":"2017","journal-title":"Mol Nutr Food Res"},{"issue":"1","key":"pone.0266135.ref023","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11357-016-9886-1","article-title":"Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli","volume":"38","author":"LA Maciel-Bar\u00f3n","year":"2016","journal-title":"Age (Dordr)."},{"issue":"2","key":"pone.0266135.ref024","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jep.2009.10.004","article-title":"Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol","volume":"127","author":"S Dugasani","year":"2010","journal-title":"J Ethnopharmacol"},{"issue":"3","key":"pone.0266135.ref025","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":"X Han","year":"2016","journal-title":"Aging Cell"},{"issue":"14","key":"pone.0266135.ref026","doi-asserted-by":"crossref","first-page":"22513","DOI":"10.18632\/oncotarget.15116","article-title":"AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema","volume":"8","author":"XY Cheng","year":"2017","journal-title":"Oncotarget"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T13:43:43Z","timestamp":1648561423000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0266135"}},"subtitle":[],"editor":[{"given":"Yong Sze","family":"Ong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0266135","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}