PUBLICATION

Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib, Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation

Authors
Hernández-Silva, D., Cantón-Sandoval, J., Martínez-Navarro, F.J., Pérez-Sánchez, H., de Oliveira, S., Mulero, V., Alcaraz-Pérez, F., Cayuela, M.L.
ID
ZDB-PUB-220924-17
Date
2022
Source
International Journal of Molecular Sciences   23(18): (Journal)
Registered Authors
de Oliveira, Sofia, Mulero, Victor
Keywords
aging, chronic inflammation, metainflammation, senolytics, zebrafish
MeSH Terms
  • Zebrafish*
  • Inflammation/drug therapy
  • Non-alcoholic Fatty Liver Disease*
  • Sulfonamides
  • Aniline Compounds
  • Dasatinib/pharmacology
  • Dasatinib/therapeutic use
  • Senotherapeutics
  • Serine Proteinase Inhibitors/pharmacology
  • Cellular Senescence
  • Anti-Inflammatory Agents/pharmacology
  • Anti-Inflammatory Agents/therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic
  • Animals
(all 14)
PubMed
36142384 Full text @ Int. J. Mol. Sci.
Abstract
Telomere shortening is the main molecular mechanism of aging, but not the only one. The adaptive immune system also ages, and older organisms tend to develop a chronic pro-inflammatory status with low-grade inflammation characterized by chronic activation of the innate immune system, called inflammaging. One of the main stimuli that fuels inflammaging is a high nutrient intake, triggering a metabolic inflammation process called metainflammation. In this study, we report the anti-inflammatory activity of several senolytic drugs in the context of chronic inflammation, by using two different zebrafish models: (i) a chronic skin inflammation model with a hypomorphic mutation in spint1a, the gene encoding the serine protease inhibitor, kunitz-type, 1a (also known as hai1a) and (ii) a non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) model with inflammation induced by a high-fat diet. Our results show that, although these models do not manifest premature aging, the senolytic drugs dasatinib, navitoclax, and venetoclax have an anti-inflammatory effect that results in the amelioration of chronic inflammation.
Genes / Markers
Figures
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Expression
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Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    hi2217TgTransgenic Insertion
    nz50TgTransgenic Insertion
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
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      Fish
      No data available
      Antibodies
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      Orthology
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      Engineered Foreign Genes
      Marker Marker Type Name
      DsRed2EFGDsRed2
      EGFPEFGEGFP
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      Citation
      Hernández-Silva, D., Cantón-Sandoval, J., Martínez-Navarro, F.J., Pérez-Sánchez, H., de Oliveira, S., Mulero, V., Alcaraz-Pérez, F., Cayuela, M.L. (2022) Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib, Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation. International Journal of Molecular Sciences. 23(18).