Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology
Aguado et al.,
Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology,
bioRxiv, doi:10.1101/2023.01.17.524329 (Preprint)
In Vitro and animal study showing that senolytics including dasatinib + quercetin improve survival and mitigate neuropathological sequelae of SARS-CoV-2.
Authors show that SARS-CoV-2 can initiate cellular senescence in the brains of COVID-19 patients and in human brain organoids, and that senolytics inhibit SARS-CoV-2 and senescence in human brain organoids.
With K18-hACE2 mice, authors show that senolytics dasatinib + quercetin, fisetin, and navitoclax improved clinical scores and mortality, and mitigated COVID-19 brain pathology. The highest survival rate was seen with dasatinib + quercetin.
6 In Vitro studies support the efficacy of quercetin
[Aguado, Bahun, Goc, Kandeil, Munafò, Singh].
Aguado et al., 18 Jan 2023, Australia, preprint, 29 authors, this trial uses multiple treatments in the treatment arm (combined with dasatinib) - results of individual treatments may vary.
Contact:
j.aguadoperez@uq.edu.au.
Abstract: bioRxiv preprint doi: https://doi.org/10.1101/2023.01.17.524329; this version posted January 18, 2023. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in
perpetuity. It is made available under aCC-BY-ND 4.0 International license.
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Senolytic therapy alleviates physiological human brain aging and COVID-19
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neuropathology.
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Julio Aguado1,*, Alberto A. Amarilla2,14, Atefeh Taherian Fard1, Eduardo A. Albornoz3, Alexander
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Tyshkovskiy4,5, Marius Schwabenland6, Harman K. Chaggar1,7, Naphak Modhiran1,2, Cecilia
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Gómez-Inclán1, Ibrahim Javed1, Alireza A. Baradar1, Benjamin Liang2, Malindrie Dharmaratne1,
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Giovanni Pietrogrande1, Pranesh Padmanabhan8, Morgan E. Freney2, Rhys Parry2, Julian D.J.
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Sng2, Ariel Isaacs2, Alexander A. Khromykh2,9, Alejandro Rojas-Fernandez10, Thomas P. Davis1,
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Marco Prinz6,11, Bertram Bengsch11,12, Vadim N. Gladyshev4,13, Trent M. Woodruff3, Jessica C.
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Mar1,14, Daniel Watterson2,14, and Ernst J. Wolvetang1,14.
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4072, Australia.
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4072.
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4072, Australia.
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School, Boston, MA 02115, USA.
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Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119234, Russia.
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Institute of Neuropathology and Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of
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Medicine, University of Freiburg, Freiburg, Germany
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Cellesce Ltd, Cardiff Medicentre, Heath Park, Cardiff, United Kingdom.
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Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of
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Queensland, Brisbane, QLD, Australia
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QLD, Australia.
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Institute of Medicine, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile.
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Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
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Faculty of Medicine, Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology,
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and Infectious Disease, University Medical Center Freiburg, Freiburg, Germany
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Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
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These authors contributed equally to this work as co-senior authors.
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*Corresponding author. Email: j.aguadoperez@uq.edu.au
Australian Institute for Biotechnology and Nanotechnology, University of Queensland, St Lucia, QLD
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia
School of Biomedical Sciences, Faculty of Medicine, University of Queensland, St Lucia, Queensland
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical
Australian Infectious Disease Research Centre, Global Virus Network Centre of Excellence, Brisbane
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bioRxiv preprint doi: https://doi.org/10.1101/2023.01.17.524329; this version posted January 18, 2023. The copyright holder for this
preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in
perpetuity. It is made available under aCC-BY-ND 4.0 International license.
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Abstract
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Aging is the primary risk factor for most neurodegenerative diseases, and recently coronavirus
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disease 2019 (COVID-19) has been associated with severe neurological manifestations that can
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eventually impact neurodegenerative conditions in the long-term. The progressive accumulation
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of senescent cells in..
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