TY - JOUR
T1 - Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib, Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation
AU - Hernández-Silva, David
AU - Cantón-Sandoval, Joaquín
AU - Martínez-Navarro, Francisco Juan
AU - Pérez-Sánchez, Horacio
AU - de Oliveira, Sofia
AU - Mulero, Victoriano
AU - Alcaraz-Pérez, Francisca
AU - Cayuela, María Luisa
N1 - Funding Information:
This research was funded by the Spanish Ministry of Science and Innovation (grants iscIII PI19/00188 to M.L.C. and BIO2017-84702-R to V.M.), all co-funded with Fondos Europeos de Desarrollo Regional (Una manera de hacer Europa), Fundación Ramón Areces (grant to M.L.C.), and University Catholic of Murcia (predoctoral contract to D.H.-S.). F.J.M.-N. is supported by the Cancer Research Institute and Fibrolamellar Cancer Foundation and Consejería de Sanidad de la Region de Murcia (Project ZEBER, contract to F.A-P.).
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - aging
KW - chronic inflammation
KW - metainflammation
KW - senolytics
KW - zebrafish
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U2 - 10.3390/ijms231810468
DO - 10.3390/ijms231810468
M3 - Article
C2 - 36142384
AN - SCOPUS:85138363340
SN - 1661-6596
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 18
M1 - 10468
ER -