Identification of gingerenone A as a novel senolytic compound

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 per...

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Veröffentlicht in:	PloS one Jg. 17; H. 3; S. e0266135
Hauptverfasser:	Moaddel, Ruin, Rossi, Martina, Rodriguez, Stephanie, Munk, Rachel, Khadeer, Mohammed, Abdelmohsen, Kotb, Gorospe, Myriam, Ferrucci, Luigi
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 29.03.2022 Public Library of Science (PLoS)
Schlagworte:	Age Aging Aging (natural) Amino acids Animal models Animals Apoptosis Atherosclerosis Auroral kilometric radiation Automation Biological products Biology and Life Sciences Cell cycle Cell death Cellular Senescence Chemical compounds Chronic illnesses Cytokines Dasatinib - pharmacology Diarylheptanoids - pharmacology Digital cameras Diseases Fibroblasts Genetics Genomics Ginger Health aspects Ionizing radiation Laboratories Materia medica, Vegetable Medicine and Health Sciences Mice Penicillin Pharmacology Phenotypes Physical Sciences Plant extracts Properties Quercetin Quercetin - pharmacology Research and analysis methods Senescence Zingiber officinale United States Minneapolis Minnesota Milpitas California United States > US Baltimore Maryland
ISSN:	1932-6203, 1932-6203
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Abstract	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 ( Zingiber officinale Rosc .) 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.
AbstractList	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 (Zingiber officinale Rosc.) 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. 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 (Zingiber officinale Rosc.) 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.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 (Zingiber officinale Rosc.) 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. 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 ( Zingiber officinale Rosc .) 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.
Audience	Academic
Author	Abdelmohsen, Kotb Gorospe, Myriam Rossi, Martina Khadeer, Mohammed Moaddel, Ruin Rodriguez, Stephanie Ferrucci, Luigi Munk, Rachel
AuthorAffiliation	2 Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America 3 Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America 1 Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America Monash University Malaysia, MALAYSIA
AuthorAffiliation_xml	– name: 1 Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America – name: 3 Translational Gerontology Branch, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America – name: 2 Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, United States of America – name: Monash University Malaysia, MALAYSIA
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SubjectTerms	Age Aging Aging (natural) Amino acids Animal models Animals Apoptosis Atherosclerosis Auroral kilometric radiation Automation Biological products Biology and Life Sciences Cell cycle Cell death Cellular Senescence Chemical compounds Chronic illnesses Cytokines Dasatinib - pharmacology Diarylheptanoids - pharmacology Digital cameras Diseases Fibroblasts Genetics Genomics Ginger Health aspects Ionizing radiation Laboratories Materia medica, Vegetable Medicine and Health Sciences Mice Penicillin Pharmacology Phenotypes Physical Sciences Plant extracts Properties Quercetin Quercetin - pharmacology Research and analysis methods Senescence Zingiber officinale
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Title	Identification of gingerenone A as a novel senolytic compound
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