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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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. 1 Senolytic therapy alleviates physiological human brain aging and COVID-19 2 neuropathology. 3 4 Julio Aguado1,*, Alberto A. Amarilla2,14, Atefeh Taherian Fard1, Eduardo A. Albornoz3, Alexander 5 Tyshkovskiy4,5, Marius Schwabenland6, Harman K. Chaggar1,7, Naphak Modhiran1,2, Cecilia 6 Gómez-Inclán1, Ibrahim Javed1, Alireza A. Baradar1, Benjamin Liang2, Malindrie Dharmaratne1, 7 Giovanni Pietrogrande1, Pranesh Padmanabhan8, Morgan E. Freney2, Rhys Parry2, Julian D.J. 8 Sng2, Ariel Isaacs2, Alexander A. Khromykh2,9, Alejandro Rojas-Fernandez10, Thomas P. Davis1, 9 Marco Prinz6,11, Bertram Bengsch11,12, Vadim N. Gladyshev4,13, Trent M. Woodruff3, Jessica C. 10 Mar1,14, Daniel Watterson2,14, and Ernst J. Wolvetang1,14. 11 12 13 1 14 4072, Australia. 15 2 16 4072. 17 3 18 4072, Australia. 19 4 20 School, Boston, MA 02115, USA. 21 5 Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119234, Russia. 22 6 Institute of Neuropathology and Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of 23 Medicine, University of Freiburg, Freiburg, Germany 24 7 Cellesce Ltd, Cardiff Medicentre, Heath Park, Cardiff, United Kingdom. 25 8 Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of 26 Queensland, Brisbane, QLD, Australia 27 9 28 QLD, Australia. 29 10 Institute of Medicine, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile. 30 11 Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany 31 12 Faculty of Medicine, Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, 32 and Infectious Disease, University Medical Center Freiburg, Freiburg, Germany 33 13 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. 34 14 These authors contributed equally to this work as co-senior authors. 35 *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 1 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. 36 Abstract 37 Aging is the primary risk factor for most neurodegenerative diseases, and recently coronavirus 38 disease 2019 (COVID-19) has been associated with severe neurological manifestations that can 39 eventually impact neurodegenerative conditions in the long-term. The progressive accumulation 40 of senescent cells in..