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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Published in:PloS one Vol. 17; no. 3; p. e0266135
Main Authors: Moaddel, Ruin, Rossi, Martina, Rodriguez, Stephanie, Munk, Rachel, Khadeer, Mohammed, Abdelmohsen, Kotb, Gorospe, Myriam, Ferrucci, Luigi
Format: Journal Article
Language:English
Published: United States Public Library of Science 29.03.2022
Public Library of Science (PLoS)
Subjects:
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
Online Access:Get full text
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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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  surname: Moaddel
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35349590$$D View this record in MEDLINE/PubMed
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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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Volume 17
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