{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:04:38Z","timestamp":1783976678737,"version":"3.55.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD019960"],"award-info":[{"award-number":["S10OD019960"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL115195-06"],"award-info":[{"award-number":["HL115195-06"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["SP00013920-02"],"award-info":[{"award-number":["SP00013920-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL137962"],"award-info":[{"award-number":["HL137962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["SP00013696-01"],"award-info":[{"award-number":["SP00013696-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ardmore Institute of Health","award":["2150141"],"award-info":[{"award-number":["2150141"]}]},{"DOI":"10.13039\/100000104","name":"NASA","doi-asserted-by":"publisher","award":["NNX15AE86G"],"award-info":[{"award-number":["NNX15AE86G"]}],"id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18IPA34170301"],"award-info":[{"award-number":["18IPA34170301"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight. The purpose of this study was to determine whether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock. The mice were flown for 37 days in animal enclosure modules on the International Space Station; ground-based control animals were maintained under similar housing conditions. Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. We found that a large number of genes were differentially methylated with spaceflight, whereas there were fewer differentially expressed genes at the transcriptome level. Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered. Our results indicated that spaceflight decelerated the retinal epigenetic clock. This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels, and such changes could be involved in the etiology of eye-related disorders among astronauts.<\/jats:p>","DOI":"10.1093\/pcmedi\/pbab012","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T06:21:59Z","timestamp":1621232519000},"page":"93-108","source":"Crossref","is-referenced-by-count":20,"title":["Spaceflight decelerates the epigenetic clock orchestrated with a global alteration in DNA methylome and transcriptome in the mouse retina"],"prefix":"10.1093","volume":"4","author":[{"given":"Zhong","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seta","family":"Stanbouly","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"},{"name":"Division of Radiation Research, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina C","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Division of Radiation Research, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Delp","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL 32306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Institute of Biomedical Science, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao W","family":"Mao","sequence":"additional","affiliation":[{"name":"Division of Radiation Research, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-2121","authenticated-orcid":false,"given":"Charles","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Genomics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"},{"name":"Division of Microbiology and Molecular Genetics, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"2022032115031053900_bib1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3389\/fphys.2017.00547","article-title":"Human pathophysiological adaptations to the space environment","volume":"8","author":"Demontis","year":"2017","journal-title":"Front Physiol"},{"key":"2022032115031053900_bib2","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/S0273-1177(99)01013-3","article-title":"CNS-induced deficits of heavy particle irradiation in space: the aging connection","volume":"25","author":"Joseph","year":"2000","journal-title":"Adv Space Res"},{"key":"2022032115031053900_bib3","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1016\/j.ophtha.2011.06.021","article-title":"Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight","volume":"118","author":"Mader","year":"2011","journal-title":"Ophthalmology"},{"key":"2022032115031053900_bib4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/pcmedi\/pbz022","article-title":"Translating current biomedical therapies for long duration, deep space missions","volume":"2","author":"Iosim","year":"2019","journal-title":"Precis Clin Med"},{"key":"2022032115031053900_bib5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1667\/RR1580.1","article-title":"NASA study of cataract in astronauts (NASCA). Report 1: Cross-sectional study of the relationship of exposure to space radiation and risk of lens opacity","volume":"172","author":"Chylack","year":"2009","journal-title":"Radiat Res"},{"key":"2022032115031053900_bib6","first-page":"A56","article-title":"Cataract formation mechanisms and risk in aviation and space crews","volume":"78","author":"Jones","year":"2007","journal-title":"Aviat Space Environ Med"},{"key":"2022032115031053900_bib7","doi-asserted-by":"crossref","first-page":"S206","DOI":"10.4103\/0028-3886.259126","article-title":"An overview of spaceflight-associated neuro-ocular syndrome (SANS)","volume":"67","author":"Mader","year":"2019","journal-title":"Neurol India"},{"key":"2022032115031053900_bib8","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.3390\/ijms19092546","article-title":"Impact of spaceflight and artificial gravity on the mouse retina: Biochemical and proteomic analysis","volume":"19","author":"Mao","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2022032115031053900_bib9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1667\/RR3309.1","article-title":"Spaceflight environment induces mitochondrial oxidative damage in ocular tissue","volume":"180","author":"Mao","year":"2013","journal-title":"Radiat Res"},{"key":"2022032115031053900_bib10","first-page":"425","article-title":"Gene expression analysis of oxidative stress and apoptosis in proton-irradiated rat retina","volume":"24","author":"Mao","year":"2010","journal-title":"In Vivo"},{"key":"2022032115031053900_bib11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1667\/RR14977.1","article-title":"Acute effect of low-dose space radiation on mouse retina and retinal endothelial cells","volume":"190","author":"Mao","year":"2018","journal-title":"Radiat Res"},{"key":"2022032115031053900_bib12","doi-asserted-by":"crossref","first-page":"8215","DOI":"10.1038\/s41598-019-44696-0","article-title":"Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations","volume":"9","author":"Mao","year":"2019","journal-title":"Sci Rep"},{"key":"2022032115031053900_bib13","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1093\/hmg\/ddq129","article-title":"Transcriptome analysis and molecular signature of human retinal pigment epithelium","volume":"19","author":"Strunnikova","year":"2010","journal-title":"Hum Mol Genet"},{"key":"2022032115031053900_bib14","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1093\/hmg\/ddu114","article-title":"Comprehensive analysis of gene expression in human retina and supporting tissues","volume":"23","author":"Li","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2022032115031053900_bib15","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ygeno.2015.01.008","article-title":"Transcriptome of the human retina, retinal pigmented epithelium and choroid","volume":"105","author":"Tian","year":"2015","journal-title":"Genomics"},{"key":"2022032115031053900_bib16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1741-7015-10-21","article-title":"Transcriptome changes in age-related macular degeneration","volume":"10","author":"Whitmore","year":"2012","journal-title":"BMC Med"},{"key":"2022032115031053900_bib17","doi-asserted-by":"crossref","first-page":"13304","DOI":"10.1038\/s41598-019-49453-x","article-title":"Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina","volume":"9","author":"Overbey","year":"2019","journal-title":"Sci Rep"},{"key":"2022032115031053900_bib18","doi-asserted-by":"crossref","first-page":"eaau8650","DOI":"10.1126\/science.aau8650","article-title":"The NASA twins study: A multidimensional analysis of a year-long human spaceflight","volume":"364","author":"Garrett-Bakelman","year":"2019","journal-title":"Science"},{"key":"2022032115031053900_bib19","doi-asserted-by":"crossref","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biol"},{"key":"2022032115031053900_bib20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13059-017-1203-5","article-title":"Multi-tissue DNA methylation age predictor in mouse","volume":"18","author":"Stubbs","journal-title":"Genome Biol"},{"key":"2022032115031053900_bib21","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.cmet.2017.03.016","article-title":"Using DNA methylation profiling to evaluate biological age and longevity interventions","volume":"25","author":"Petkovich","year":"2017","journal-title":"Cell Metab"},{"key":"2022032115031053900_bib22","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigenetic clock theory of ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nat Rev Genet"},{"key":"2022032115031053900_bib23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41526-020-0097-9","article-title":"Spaceflight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update","volume":"6","author":"Lee","year":"2020","journal-title":"NPJ Microgravity"},{"key":"2022032115031053900_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.01.005","article-title":"Vision from next generation sequencing: multi-dimensional genome-wide analysis for producing gene regulatory networks underlying retinal development, aging and disease","volume":"46","author":"Yang","year":"2015","journal-title":"Prog Retin Eye Res"},{"key":"2022032115031053900_bib25","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/pcmedi\/pbaa022","article-title":"Long-term spaceflight and the cardiovascular system","volume":"3","author":"Vernice","year":"2020","journal-title":"Precis Clin Med"},{"key":"2022032115031053900_bib26","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.cell.2020.11.002","article-title":"Comprehensive multi-omics analysis reveals mitochondrial stress as a central biological hub for spaceflight impact","volume":"183","author":"da\u00a0Silveira","year":"2020","journal-title":"Cell"},{"key":"2022032115031053900_bib27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.exer.2014.11.001","article-title":"Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE\/choroid by RNA-Seq","volume":"129","author":"Whitmore","year":"2014","journal-title":"Exp Eye Res"},{"key":"2022032115031053900_bib28","doi-asserted-by":"crossref","first-page":"13094","DOI":"10.1073\/pnas.2000339117","article-title":"Altered photoreceptor metabolism in mouse causes late stage-related macular degeneration-like pathologies","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022032115031053900_bib29","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/nrd3599","article-title":"Taking aim at the extracellular matrix: ccn proteins as emerging therapeutic targets","volume":"10","author":"Jun","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"2022032115031053900_bib30","doi-asserted-by":"crossref","first-page":"525","DOI":"10.5483\/BMBRep.2015.48.9.140","article-title":"Wnt5a attenuates the pathogenic effects of the Wnt\/beta-catenin pathway in human retinal pigment epithelial cells via down-regulating beta-catenin and Snail","volume":"48","author":"Kim","year":"2015","journal-title":"BMB Rep"},{"key":"2022032115031053900_bib31","doi-asserted-by":"crossref","first-page":"e13302","DOI":"10.14814\/phy2.13302","article-title":"Effects of short-term mild hypercapnia during head-down tilt on intracranial pressure and ocular structures in healthy human subjects","volume":"5","author":"Laurie","year":"2017","journal-title":"Physiol Rep"},{"key":"2022032115031053900_bib32","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1167\/iovs.18-23885","article-title":"Ultrastructural morphology of the optic nerve head in aged and glaucomatous mice","volume":"59","author":"Zhu","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2022032115031053900_bib33","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1172\/JCI37762","article-title":"Toward unraveling the complexity of simple epithelial keratins in human disease","volume":"119","author":"Omary","year":"2009","journal-title":"J Clin Invest"},{"key":"2022032115031053900_bib34","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3109\/02713689409025135","article-title":"Expression of keratins K12, K4 and K14 during development of ocular surface epithelium","volume":"13","author":"Kurpakus","year":"1994","journal-title":"Curr Eye Res"},{"key":"2022032115031053900_bib35","first-page":"1309","article-title":"Evaluation of EGR1 as a candidate gene for high myopia","volume":"14","author":"Li","year":"2008","journal-title":"Mol Vis"},{"key":"2022032115031053900_bib36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2013.08.055","article-title":"Retinoic acid signaling is essential for embryonic hematopoietic stem cell development","volume":"155","author":"Chanda","year":"2013","journal-title":"Cell"},{"key":"2022032115031053900_bib37","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.exer.2009.04.012","article-title":"Retinoic acid signaling in mammalian eye development","volume":"89","author":"Cvekl","year":"2009","journal-title":"Exp Eye Res"},{"key":"2022032115031053900_bib38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2018.03.002","article-title":"Epigenetic control of gene regulation during development and disease: A view from the retina","volume":"65","author":"Corso-Diaz","year":"2018","journal-title":"Prog Retin Eye Res"},{"key":"2022032115031053900_bib39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2478\/gsr-2014-0001","article-title":"Molecular effects of spaceflight in the mouse eye after space shuttle mission STS-135","volume":"2","author":"Theriot","year":"2014","journal-title":"Gravitat Space Res"},{"key":"2022032115031053900_bib40","author":"TrimGalore"},{"key":"2022032115031053900_bib41","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"2022032115031053900_bib42","doi-asserted-by":"crossref","first-page":"R87","DOI":"10.1186\/gb-2012-13-10-r87","article-title":"methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles","volume":"13","author":"Akalin","year":"2012","journal-title":"Genome Biol"},{"key":"2022032115031053900_bib43","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1093\/bioinformatics\/btu126","article-title":"DMAP: differential methylation analysis package for RRBS and WGBS data","volume":"30","author":"Stockwell","year":"2014","journal-title":"Bioinformatics"},{"key":"2022032115031053900_bib44","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/nbt.3001","article-title":"The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance","volume":"32","author":"Wang","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2022032115031053900_bib45","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1038\/ncomms4230","article-title":"A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages","volume":"5","author":"Yu","year":"2014","journal-title":"Nat Commun"},{"key":"2022032115031053900_bib46","volume-title":"FastQC: A quality control tool for high throughput sequence data","author":"Andrews","year":"2010"},{"key":"2022032115031053900_bib47","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1093\/bioinformatics\/btp450","article-title":"ShortRead: a bioconductor package for input, quality assessment and exploration of high-throughput sequence data","volume":"25","author":"Morgan","year":"2009","journal-title":"Bioinformatics"},{"key":"2022032115031053900_bib48","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2022032115031053900_bib49","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol"},{"key":"2022032115031053900_bib50","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat Biotechnol"},{"key":"2022032115031053900_bib51","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nprot.2012.016","article-title":"Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks","volume":"7","author":"Trapnell","year":"2012","journal-title":"Nat Protoc"}],"container-title":["Precision Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/pcm\/advance-article-pdf\/doi\/10.1093\/pcmedi\/pbab012\/38659657\/pbab012.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pcm\/article-pdf\/4\/2\/93\/42965700\/pbab012.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pcm\/article-pdf\/4\/2\/93\/42965700\/pbab012.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T11:09:37Z","timestamp":1647860977000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pcm\/article\/4\/2\/93\/6276723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,6,23]]}},"URL":"https:\/\/doi.org\/10.1093\/pcmedi\/pbab012","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.10.23.352658","asserted-by":"object"}]},"ISSN":["2096-5303","2516-1571"],"issn-type":[{"value":"2096-5303","type":"print"},{"value":"2516-1571","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6]]},"published":{"date-parts":[[2021,5,17]]}}}