{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:13:38Z","timestamp":1790432018009,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004007","name":"Instituto Nazionale di Fisica Nucleare","doi-asserted-by":"publisher","award":["HIBRAD"],"award-info":[{"award-number":["HIBRAD"]}],"id":[{"id":"10.13039\/501100004007","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as \u201csynthetic torpor\u201d in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Here we show the preliminary results from an experiment in rats exposed to ionizing radiation in normothermic conditions or synthetic torpor. Animals were irradiated with 3 Gy X-rays and organs were collected 4 h after exposure. Histological analysis of liver and testicle showed a reduced toxicity in animals irradiated in torpor compared to controls irradiated at normal temperature and metabolic activity. The expression of ataxia telangiectasia mutated (ATM) in the liver was significantly downregulated in the group of animal in synthetic torpor. In the testicle, more genes involved in the DNA damage signaling were downregulated during synthetic torpor. These data show for the first time that synthetic torpor is a radioprotector in non-hibernators, similarly to natural torpor in hibernating animals. Synthetic torpor can be an effective strategy to protect humans during long term space exploration of the solar system.<\/jats:p>","DOI":"10.3390\/ijms20020352","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T03:09:13Z","timestamp":1547608153000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor"],"prefix":"10.3390","volume":"20","author":[{"given":"Walter","family":"Tinganelli","sequence":"first","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, Biophysics Department, Planckstra\u00dfe 1, 64291 Darmstadt, Germany"},{"name":"TIFPA, Trento Institute for Fundamentals Physics and Applications, Istituto Nazionale Fisica Nucleare, Via Sommarive 14-38123 Povo, TN, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timna","family":"Hitrec","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Romani","sequence":"additional","affiliation":[{"name":"Medical Physics, S.Orsola Malpighi University Hospital, Via Massarenti, 9-40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palma","family":"Simoniello","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, Parthenope University of Naples, Centro Direzionale isola C4, 80143 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Squarcio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Stanzani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences; Alma Mater Studiorum, University of Bologna, Via Tolara di Sopra, 50, Ozzano dell\u2019Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Piscitiello","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Marchesano","sequence":"additional","affiliation":[{"name":"TIFPA, Trento Institute for Fundamentals Physics and Applications, Istituto Nazionale Fisica Nucleare, Via Sommarive 14-38123 Povo, TN, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-5014","authenticated-orcid":false,"given":"Marco","family":"Luppi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano","family":"Sioli","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Fisica Nucleare, Sezione di Bologna. Via Irnerio, 46, 40126 Bologna, Italy"},{"name":"Department of Physics and Astronomy; Alma Mater Studiorum, University of Bologna, Via Irnerio, 46, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Helm","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, Biophysics Department, Planckstra\u00dfe 1, 64291 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Compagnone","sequence":"additional","affiliation":[{"name":"Medical Physics, S.Orsola Malpighi University Hospital, Via Massarenti, 9-40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio G.","family":"Morganti","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine; Alma Mater Studiorum, University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Amici","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Negrini","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Fisica Nucleare, Sezione di Bologna. Via Irnerio, 46, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Zoccoli","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Fisica Nucleare, Sezione di Bologna. Via Irnerio, 46, 40126 Bologna, Italy"},{"name":"Department of Physics and Astronomy; Alma Mater Studiorum, University of Bologna, Via Irnerio, 46, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-553X","authenticated-orcid":false,"given":"Marco","family":"Durante","sequence":"additional","affiliation":[{"name":"GSI Helmholtzzentrum f\u00fcr Schwerionenforschung, Biophysics Department, Planckstra\u00dfe 1, 64291 Darmstadt, Germany"},{"name":"Technische Universit\u00e4t Darmstadt, Institut f\u00fcr Festk\u00f6rperphysik, Hochschulstra\u00dfe 6, 64289 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-305X","authenticated-orcid":false,"given":"Matteo","family":"Cerri","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Physiology; Alma Mater Studiorum, University of Bologna, Piazza di Porta S.Donato, 2, 40126 Bologna, Italy"},{"name":"Istituto Nazionale Fisica Nucleare, Sezione di Bologna. Via Irnerio, 46, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.resp.2004.03.014","article-title":"Natural hypometabolism during hibernation and daily torpor in mammals","volume":"141","author":"Heldmaier","year":"2004","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev.physiol.66.032102.115105","article-title":"Metabolic rate and body temperature reduction during hibernation and daily torpor","volume":"66","author":"Geiser","year":"2004","journal-title":"Annu. Rev. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cbpa.2007.02.041","article-title":"Ontogeny and phylogeny of endothermy and torpor in mammals and birds","volume":"150","author":"Geiser","year":"2008","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/icb\/icu002","article-title":"The evolution of mammalian hibernation: Lessons from comparative acid-base physiology","volume":"54","author":"Malan","year":"2014","journal-title":"Integr. Comp. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.med.59.061506.110403","article-title":"Is human hibernation possible?","volume":"59","author":"Lee","year":"2008","journal-title":"Annu. Rev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1002\/jcp.22850","article-title":"Induction of torpor: Mimicking natural metabolic suppression for biomedical applications","volume":"227","author":"Bouma","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-physiol-022516-034133","article-title":"The Central Control of Energy Expenditure: Exploiting Torpor for Medical Applications","volume":"79","author":"Cerri","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lssr.2016.09.001","article-title":"Hibernation for space travel: Impact on radioprotection","volume":"11","author":"Cerri","year":"2016","journal-title":"Life Sci. Space Res. (Amst.)"},{"key":"ref_9","unstructured":"(2018, November 14). ESA Advanced Concept Team. Available online: https:\/\/www.esa.int\/gsp\/ACT\/projects\/hibernation.html."},{"key":"ref_10","unstructured":"Seedhouse, E., and Shayler, D. (2018). Hibernation and Torpor: Prospects for Human Spaceflight. Handbook of Life Support Systems for Spacecraft and Extraterrestrial Habitats, Springer."},{"key":"ref_11","first-page":"3615","article-title":"Beyond astronaut\u2019s capabilities: The current state of the art","volume":"2015","author":"Gemignani","year":"2015","journal-title":"Conf. Proc. IEEE Eng. Med. Biol. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"348","DOI":"10.2307\/3572485","article-title":"Survival of whole-body-irradiated hibernating and active ground squirrels; Citellus tridecemlineatus","volume":"33","author":"Musacchia","year":"1968","journal-title":"Radiat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrc2391","article-title":"Heavy ion carcinogenesis and human space exploration","volume":"8","author":"Durante","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.lssr.2014.01.002","article-title":"Space radiation protection: Destination Mars","volume":"1","author":"Durante","year":"2014","journal-title":"Life Sci. Space Res. (Amst.)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1126\/science.1235989","article-title":"Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory","volume":"340","author":"Zeitlin","year":"2013","journal-title":"Science"},{"key":"ref_16","first-page":"485","article-title":"The potential application of hibernation to space travel","volume":"31","author":"Hock","year":"1960","journal-title":"Aerosp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1001\/jama.1962.03050490001001","article-title":"Protective effects of hypothermia in exploration of space","volume":"182","author":"Cockett","year":"1962","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2307\/3572780","article-title":"Survival of hibernating ground squirrels (Citellus tridecemlineatus) after single and fractionated doses of cobalt-60 gamma radiation","volume":"38","author":"Jaroslow","year":"1969","journal-title":"Radiat. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2307\/3572785","article-title":"The effect of body temperature and postirradiation cold exposure on the radiation response of the hibernator Citellus tridecemlineatus","volume":"38","author":"Barr","year":"1969","journal-title":"Radiat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2307\/3573026","article-title":"Radioresistance in hamsters during hypothermic depressed metabolism induced with helium and low temperatures","volume":"46","author":"Musacchia","year":"1971","journal-title":"Radiat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14900","DOI":"10.1038\/s41598-017-15002-7","article-title":"Pharmacologically induced reversible hypometabolic state mitigates radiation induced lethality in mice","volume":"7","author":"Ghosh","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.mrfmmm.2010.12.006","article-title":"Hypothermia postpones DNA damage repair in irradiated cells and protects against cell killing","volume":"711","author":"Baird","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1523\/JNEUROSCI.3596-12.2013","article-title":"The inhibition of neurons in the central nervous pathways for thermoregulatory cold defense induces a suspended animation state in the rat","volume":"33","author":"Cerri","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.cmet.2014.02.007","article-title":"Central neural regulation of brown adipose tissue thermogenesis and energy expenditure","volume":"19","author":"Morrison","year":"2014","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.lssr.2018.01.002","article-title":"Synthetic torpor: A method for safely and practically transporting experimental animals aboard spaceflight missions to deep space","volume":"16","author":"Griko","year":"2018","journal-title":"Life Sci. Space Res. (Amst.)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3109\/09553002.2012.679383","article-title":"Effect of hypothermia on cells\u2014A multiparametric approach to delineate the mechanisms","volume":"88","author":"Dang","year":"2012","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1080\/09553002.2018.1466206","article-title":"Hypothermia modulates the DNA damage response to ionizing radiation in human peripheral blood lymphocytes","volume":"94","author":"Lisowska","year":"2018","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.280.5366.1089","article-title":"Requirement for ATM in ionizing radiation-induced cell death in the developing central nervous system","volume":"280","author":"Herzog","year":"1998","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/s41419-018-1095-7","article-title":"Sensitivity of CD3\/CD28-stimulated versus non-stimulated lymphocytes to ionizing radiation and genotoxic anticancer drugs: Key role of ATM in the differential radiation response","volume":"9","author":"Heylmann","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.fsi.2018.09.023","article-title":"Histopathological analysis and the immune related gene expression profiles of mandarinfish (Siniperca chuatsi) infected with Aeromonas hydrophila","volume":"83","author":"Chen","year":"2018","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1477-3155-10-5","article-title":"Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration","volume":"10","author":"Abdelhalim","year":"2012","journal-title":"J. Nanobiotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1073\/pnas.1416031112","article-title":"ATM prevents DSB formation by coordinating SSB repair and cell cycle progression","volume":"112","author":"Khoronenkova","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elsevier. [6th ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0006-8993(00)03210-8","article-title":"Raphe region mediates changes in cutaneous vascular tone elicited by stimulation of amygdala and hypothalamus in rabbits","volume":"891","author":"Nalivaiko","year":"2001","journal-title":"Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/2\/352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:26:23Z","timestamp":1760185583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/2\/352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20020352"],"URL":"https:\/\/doi.org\/10.3390\/ijms20020352","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,16]]}}}