Aging cell publish this investigation article

March 1^st, 2023

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool

Pastor-Fernandez A., Rodriguez-Bertos A., Sierra-Ramirez A., del Moral-Salmoral J., Merino J., de Avila AI., Olague C., Villares R., Gonzalez-Aseguinolaza G., Rodriguez MA., Fresno M., Girones N., Bustos M., Smerdou C., Fernandez-Marcos PJ. and von Kobbe C.

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice

	Metabolic Syndrome Group-BIOPROMET. Madrid Institute for Advanced Studies-IMDEA Food.
	Servicio de Patología y Veterinaria Forense (SAP). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).
	Departamento de Medicina y Cirugía Animal. Facultad de Veterinaria. Universidad Complutense (UCM).
	Departamento de Biología Molecular. Universidad Autónoma de Madrid (UAM).
	Centro de Biología Molecular Severo Ochoa (CBMSO). Consejo Superior de Investigaciones Científicas (CSIC). Universidad Autónoma de Madrid (UAM).
	Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD). Instituto de Salud Carlos III (ISCIII).
	Division of Gene Therapy and Regulation of Gene Expression. Centro de Investigación Médica Aplicada (CIMA). Universidad de Navarra.
	Centro Nacional de Biotecnología (CNB). Consejo Superior de Investigaciones Científicas (CSIC).
	Biomedical Institute of Sevilla (IBiS). Consejo Superior de Investigaciones Científicas (CSIC). University Hospital Virgen del Rocío.
	Virgen del Rocio Universitary Hospital. Universidad de Sevilla (US).