Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib, Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation
- Hernández-Silva, D., Cantón-Sandoval, J., Martínez-Navarro, F.J., Pérez-Sánchez, H., de Oliveira, S., Mulero, V., Alcaraz-Pérez, F., Cayuela, M.L.
- International Journal of Molecular Sciences 23(18): (Journal)
- Registered Authors
- de Oliveira, Sofia, Mulero, Victor
- aging, chronic inflammation, metainflammation, senolytics, zebrafish
- MeSH Terms
- Aniline Compounds
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use
- Bridged Bicyclo Compounds, Heterocyclic
- Cellular Senescence
- Dasatinib/therapeutic use
- Inflammation/drug therapy
- Non-alcoholic Fatty Liver Disease*
- Serine Proteinase Inhibitors/pharmacology
- 36142384 Full text @ Int. J. Mol. Sci.
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).
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes