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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Zusammenfassung: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.
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Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0266135