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Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

Franco Cortese, Dmitry Klokov, Andreyan Osipov, Jakub Stefaniak, Alexey Moskalev, Jane Schastnaya, Charles Cantor, Alexander Aliper, Polina Mamoshina, Igor Ushakov, Alex Sapetsky, Quentin Vanhaelen, Irina Alchinova, Mikhail Karganov, Olga Kovalchuk, Ruth Wilkins, Andrey Shtemberg, Marjan Moreels, Sarah Baatout, Evgeny Izumchenko, João Pedro de Magalhães, Artem V. Artemov, Sylvain V. Costes, Afshin Beheshti, Xiao Wen Mao, Michael J. Pecaut, Dmitry Kaminskiy, Ivan V. Ozerov, _ Morten Scheibye-Knudsen, Alex Zhavoronkov

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Oncotarget. 2018; 9:14692-14722. https://doi.org/10.18632/oncotarget.24461

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Abstract

Franco Cortese1,2, Dmitry Klokov3,4, Andreyan Osipov5,6,7, Jakub Stefaniak1,8, Alexey Moskalev7,9,10, Jane Schastnaya5, Charles Cantor11, Alexander Aliper5,12, Polina Mamoshina5,13, Igor Ushakov6, Alex Sapetsky6, Quentin Vanhaelen5, Irina Alchinova14,15, Mikhail Karganov14, Olga Kovalchuk16,17, Ruth Wilkins18, Andrey Shtemberg19, Marjan Moreels20, Sarah Baatout20,21, Evgeny Izumchenko5,22, João Pedro de Magalhães1,23, Artem V. Artemov5, Sylvain V. Costes24, Afshin Beheshti25,26, Xiao Wen Mao27, Michael J. Pecaut27, Dmitry Kaminskiy1,28, Ivan V. Ozerov5,6, Morten Scheibye-Knudsen29 and Alex Zhavoronkov1,5

1Biogerontology Research Foundation, London, UK

2Department of Biomedical and Molecular Sciences, Queen’s University School of Medicine, Queen’s University, Kingston, Ontario, Canada

3Canadian Nuclear Laboratories, Chalk River, Ontario, Canada

4Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada

5Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University, Baltimore, MD, USA

6State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russia

7Moscow Institute of Physics and Technology, Dolgoprudny, Russia

8Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, UK

9Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, Russia

10Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, Russia

11Boston University, Department of Biomedical Engineering, Boston, MA, USA

12Laboratory of Bioinformatics, D. Rogachev Federal Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia

13Computer Science Department, University of Oxford, Oxford, UK

14Laboratory of Physicochemical and Ecological Pathophysiology, Institute of General Pathology and Pathophysiology, Moscow, Russia

15Research Institute for Space Medicine, Federal Medical Biological Agency, Moscow, Russia

16Canada Cancer and Aging Research Laboratories, Ltd., Lethbridge, Alberta, Canada

17University of Lethbridge, Lethbridge, Alberta, Canada

18Environmental and Radiation and Health Sciences Directorate, Health Canada, Ottawa, Ontario, Canada

19Laboratory of Extreme Physiology, Institute of Medical and Biological Problems RAS, Moscow, Russia

20Radiobiology Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre, (SCK·CEN), Mol, Belgium

21Department of Molecular Biotechnology, Ghent University, Ghent, Belgium

22The Johns Hopkins University, School of Medicine, Department of Otolaryngology, Head and Neck Cancer Research, Baltimore, MD, USA

23Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK

24NASA Ames Research Center, Moffett Field, CA, USA

25Wyle Laboratories, Space Biosciences Division, NASA Ames Research Center, Mountain View, CA, USA

26Division of Hematology/Oncology, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA

27Department of Basic Sciences, Division of Biomedical Engineering Sciences (BMES), Loma Linda University, Loma Linda, CA, USA

28Deep Knowledge Life Sciences, London, UK

29Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark

Correspondence to:

Ivan V. Ozerov, email: ivan@insilicomedicine.com

Morten Scheibye-Knudsen, email: mscheibye@sund.ku.dk

Alex Zhavoronkov, email: alex@insilico.com

Keywords: radioresistance; space exploration; longevity; DNA damage; Mars mission

Received: October 20, 2017    Accepted: January 31, 2018    Epub: February 12, 2018    Published: March 06, 2018

ABSTRACT

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.


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