Senolytic effects of a modified Gingerenone A

Senescent cells accumulate with aging and are associated with several age-associated diseases and functional declines. Eliminating senescent cells with senolytics improves aging phenotypes in mouse models and may improve the health of people with chronic diseases. To date, very few senotherapeutic (senolytics and senomorphics) compounds have been identified. In a recent study, we reported that gingerenone A (GinA) has a senolytic effect via mechanisms including the activation of caspase-3 activity and apoptotic cell death. In this study, we investigated whether GinA has senotherapeutic properties in a mouse model of senescence. Moreover, we modified GinA with eicosapentaenoic acid (EPA) esters (GinA-EPA) or docosahexaenoic acid (DHA) esters (GinA-DHA) to generate modified gingerenone A (modGinA) that could enhance GinA effects. We found that both GinA and modGinA induced biochemical and histological changes consistent with anti-inflammatory, senolytic, and senomorphic effects, leading to improved metabolic and mitochondrial functions.

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Publication Details

Journal
npj Aging
Published
2025-05-30
DOI
https://doi.org/10.1038/s41514-025-00230-3
Citations
1
Primary Topic
Immune cells in cancer
Type
article
Field-Weighted Citation Impact
0.80

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Senolytic effects of a modified Gingerenone A

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1 citations
npj Aging
Immune cells in cancer
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Senolytic effects of a modified Gingerenone A

Josephine Mary Egan, Ross A. McDevitt, Chang‐Yi Cui, Ruin Moaddel, Mohammed Khadeer, Nathan L. Price, Gregory S. Keyes, Rafael de Cabo, Myriam Gorospe, Luigi Ferrucci, Caio Henrique Mazucanti, Julián Candia, Christopher E. Ramsden, Chad Sanehira, Reza Ahmadkhania, Sarah Eckroth, Bryce Middleton
article en
1 citations

Abstract

Senescent cells accumulate with aging and are associated with several age-associated diseases and functional declines. Eliminating senescent cells with senolytics improves aging phenotypes in mouse models and may improve the health of people with chronic diseases. To date, very few senotherapeutic (senolytics and senomorphics) compounds have been identified. In a recent study, we reported that gingerenone A (GinA) has a senolytic effect via mechanisms including the activation of caspase-3 activity and apoptotic cell death. In this study, we investigated whether GinA has senotherapeutic properties in a mouse model of senescence. Moreover, we modified GinA with eicosapentaenoic acid (EPA) esters (GinA-EPA) or docosahexaenoic acid (DHA) esters (GinA-DHA) to generate modified gingerenone A (modGinA) that could enhance GinA effects. We found that both GinA and modGinA induced biochemical and histological changes consistent with anti-inflammatory, senolytic, and senomorphic effects, leading to improved metabolic and mitochondrial functions.

npj AgingVol. 11(1)
Institute on Aging (US), National Institute on Aging (US)
National Institutes of Health, National Institute on Aging
Good health and well-being
Openalex Percentile: Top 28%
Immune cells in cancer
0.80
DOIOpen Access PDFOpenAlex
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