{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:57:31Z","timestamp":1791845851810,"version":"4.3.4"},"reference-count":130,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ageing Research Reviews"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.arr.2024.102227","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T16:32:40Z","timestamp":1707582760000},"page":"102227","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Cosmic chronometers: Is spaceflight a catalyst for biological ageing?"],"prefix":"10.1016","volume":"95","author":[{"given":"Manuela","family":"Campisi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Cannella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Pavanello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.arr.2024.102227_bib1","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14061","article-title":"Differential MicroRNA expression following head-down tilt bed rest: implications for cardiovascular responses to microgravity","volume":"7","author":"Ade","year":"2019","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.arr.2024.102227_bib2","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.cell.2020.10.050","article-title":"Fundamental biological features of spaceflight: advancing the field to enable deep-space exploration","volume":"183","author":"Afshinnekoo","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib3","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/japplphysiol.00799.2015","article-title":"Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults","volume":"120","author":"Arentson-Lantz","year":"2016","journal-title":"J. Appl. Physiol. (1985)"},{"key":"10.1016\/j.arr.2024.102227_bib4","doi-asserted-by":"crossref","DOI":"10.1093\/femsle\/fnac049","article-title":"A designer diet layout for astronauts using a microbiome mediated approach.","volume":"369","author":"Arora","year":"2022","journal-title":"FEMS Microbiol. Lett."},{"key":"10.1016\/j.arr.2024.102227_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/npjmgrav.2016.39","article-title":"Spaceflight modulates gene expression in the whole blood of astronauts","volume":"2","author":"Barrila","year":"2016","journal-title":"npj Microgravity"},{"key":"10.1016\/j.arr.2024.102227_bib6","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.2337\/db11-1300","article-title":"The critical role of metabolic pathways in aging","volume":"61","author":"Barzilai","year":"2012","journal-title":"Diabetes"},{"key":"10.1016\/j.arr.2024.102227_bib7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13059-019-1824-y","article-title":"DNA methylation aging clocks: challenges and recommendations","volume":"20","author":"Bell","year":"2019","journal-title":"Genome Biol."},{"key":"10.1016\/j.arr.2024.102227_bib8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00439-019-02094-6","article-title":"Alternative splicing in aging and longevity","volume":"139","author":"Bhadra","year":"2020","journal-title":"Hum. Genet"},{"key":"10.1016\/j.arr.2024.102227_bib9","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1093\/ajcn\/88.4.950","article-title":"Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest","volume":"88","author":"Biolo","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.arr.2024.102227_bib10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/nyas.12998","article-title":"Mindfulness meditation and the immune system: a systematic review of randomized controlled trials","volume":"1373","author":"Black","year":"2016","journal-title":"Ann. N. Y Acad. Sci."},{"key":"10.1016\/j.arr.2024.102227_bib11","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.aab3389","article-title":"Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection","volume":"350","author":"Blackburn","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.arr.2024.102227_bib12","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1152\/japplphysiol.01077.2013","article-title":"Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation","volume":"116","author":"Boesen","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib13","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1113\/jphysiol.2012.240267","article-title":"The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms","volume":"590","author":"Brocca","year":"2012","journal-title":"J. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib14","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.7150\/ijms.9694","article-title":"Influence of exercise on the metabolic profile caused by 28 days of bed rest with energy deficit and amino acid supplementation in healthy men","volume":"11","author":"Brooks","year":"2014","journal-title":"Int J. Med Sci."},{"key":"10.1016\/j.arr.2024.102227_bib15","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/mus.21780","article-title":"Effects of resistance exercise combined with essential amino acid supplementation and energy deficit on markers of skeletal muscle atrophy and regeneration during bed rest and active recovery","volume":"42","author":"Brooks","year":"2010","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.arr.2024.102227_bib16","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/nrm2233","article-title":"Cellular senescence: when bad things happen to good cells","volume":"8","author":"Campisi","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.arr.2024.102227_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2023.101909","article-title":"Long-term human spaceflight and inflammaging: Does it promote aging?","volume":"87","author":"Capri","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.arr.2024.102227_bib18","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1096\/fj.201801625R","article-title":"Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting","volume":"33","author":"Capri","year":"2019","journal-title":"FASEB J."},{"key":"10.1016\/j.arr.2024.102227_bib19","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkn1027","article-title":"Telomere length measurement by a novel monochrome multiplex quantitative PCR method","volume":"37","author":"Cawthon","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.arr.2024.102227_bib20","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/30.10.e47","article-title":"Telomere measurement by quantitative PCR","volume":"30","author":"Cawthon","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.arr.2024.102227_bib21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1152\/physiolgenomics.00036.2009","article-title":"Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures","volume":"38","author":"Chopard","year":"2009","journal-title":"Physiol. Genom."},{"key":"10.1016\/j.arr.2024.102227_bib22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cell.2007.07.003","article-title":"Cellular senescence in cancer and aging","volume":"130","author":"Collado","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbi.2018.03.003","article-title":"Insight meditation and telomere biology: the effects of intensive retreat and the moderating role of personality","volume":"70","author":"Conklin","year":"2018","journal-title":"Brain, Behav., Immun."},{"key":"10.1016\/j.arr.2024.102227_bib24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1089\/space.2020.0048","article-title":"Earth-based research analogs to investigate space-based health risks","volume":"9","author":"Cromwell","year":"2021","journal-title":"N. Space"},{"key":"10.1016\/j.arr.2024.102227_bib25","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s10875-012-9824-7","article-title":"Immune system dysregulation occurs during short duration spaceflight on board the space shuttle","volume":"33","author":"Crucian","year":"2013","journal-title":"J. Clin. Immunol."},{"issue":"1","key":"10.1016\/j.arr.2024.102227_bib26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/npjmgrav.2015.13","article-title":"Alterations in adaptive immunity persist during long-duration spaceflight","volume":"1","author":"Crucian","year":"2015","journal-title":"npj Microgravity"},{"key":"10.1016\/j.arr.2024.102227_bib27","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1089\/jir.2013.0129","article-title":"Plasma cytokine concentrations indicate that in vivo hormonal regulation of immunity is altered during long-duration spaceflight","volume":"34","author":"Crucian","year":"2014","journal-title":"J. Interferon Cytokine Res."},{"key":"10.1016\/j.arr.2024.102227_bib28","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0096099","article-title":"Space radiation risks for astronauts on multiple international space station missions","volume":"9","author":"Cucinotta","year":"2014","journal-title":"PLOS ONE"},{"key":"10.1016\/j.arr.2024.102227_bib29","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 Silveira","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib30","first-page":"97","article-title":"Exercise and Testosterone countermeasures to mitigate metabolic changes during bed rest","volume":"26","author":"Downs","year":"2020","journal-title":"Life Sci. Space Res (Amst. )"},{"key":"10.1016\/j.arr.2024.102227_bib31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000076288","article-title":"Chromosome aberration dosimetry in cosmonauts after single or multiple space flights","volume":"103","author":"Durante","year":"2004","journal-title":"Cytogenet. Genome Res."},{"key":"10.1016\/j.arr.2024.102227_bib32","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1093\/gerona\/glu055","article-title":"Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity","volume":"69","author":"Epel","year":"2014","journal-title":"J. Gerontol.: Ser. A"},{"key":"10.1016\/j.arr.2024.102227_bib33","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.tcb.2020.05.003","article-title":"Classical and nonclassical intercellular communication in senescence and ageing","volume":"30","author":"Fafi\u00e1n-Labora","year":"2020","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.arr.2024.102227_bib34","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0273-1177(01)00011-4","article-title":"Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on MIR station","volume":"27","author":"Fedorenko","year":"2001","journal-title":"Adv. Space Res."},{"key":"10.1016\/j.arr.2024.102227_bib35","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1038\/s41598-021-84242-5","article-title":"Predicting chromosome damage in astronauts participating in international space station missions","volume":"11","author":"Feiveson","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2024.102227_bib36","doi-asserted-by":"crossref","first-page":"7958","DOI":"10.1096\/fj.201902976R","article-title":"Three months of bed rest induce a residual transcriptomic signature resilient to resistance exercise countermeasures","volume":"34","author":"Fernandez-Gonzalo","year":"2020","journal-title":"FASEB J."},{"key":"10.1016\/j.arr.2024.102227_bib37","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.it.2017.08.002","article-title":"Exosomes, DAMPs and miRNA: features of stress physiology and immune homeostasis","volume":"38","author":"Fleshner","year":"2017","journal-title":"Trends Immunol."},{"key":"10.1016\/j.arr.2024.102227_bib38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1126\/science.1172539","article-title":"Extending healthy life span--from yeast to humans","volume":"328","author":"Fontana","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.arr.2024.102227_bib39","doi-asserted-by":"crossref","first-page":"10604","DOI":"10.1073\/pnas.0500398102","article-title":"Epigenetic differences arise during the lifetime of monozygotic twins","volume":"102","author":"Fraga","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.arr.2024.102227_bib40","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune\u2013metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.arr.2024.102227_bib41","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13148-019-0656-7","article-title":"The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis","volume":"11","author":"Fransquet","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"10.1016\/j.arr.2024.102227_bib42","doi-asserted-by":"crossref","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":"10.1016\/j.arr.2024.102227_bib43","doi-asserted-by":"crossref","unstructured":"George, K., Chappell, L.J., Cucinotta, F.A., 2010. Persistence of space radiation induced cytogenetic damage in the blood lymphocytes of astronauts. Mutation Research\/Genetic Toxicology and Environmental Mutagenesis, New Insights into Chromosomal Aberrations \u2013 Reports from the 9th International Symposium on Chromosomal Aberrations 701, 75\u201379. http:\/\/dx.doi.org\/10.1016\/j.mrgentox.2010.02.007.","DOI":"10.1016\/j.mrgentox.2010.02.007"},{"key":"10.1016\/j.arr.2024.102227_bib44","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000077498","article-title":"Chromosome aberrations of clonal origin are present in astronauts\u2019 blood lymphocytes","volume":"104","author":"George","year":"2004","journal-title":"Cytogenet. Genome Res."},{"issue":"6","key":"10.1016\/j.arr.2024.102227_bib45","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1667\/0033-7587(2001)156[0731:CAITBL]2.0.CO;2","article-title":"Chromosome Aberrations in the Blood Lymphocytes of Astronauts after Space Flight","volume":"156","author":"George","year":"2001","journal-title":"Radiat Res."},{"key":"10.1016\/j.arr.2024.102227_bib46","doi-asserted-by":"crossref","unstructured":"George, K., Rhone, J., Beitman, A., Cucinotta, F.A., 2013. Cytogenetic damage in the blood lymphocytes of astronauts: Effects of repeat long-duration space missions. Mutat. Res. \/Genet. Toxicol. Environ. Mutagen., DNA Damage Chromosom. Aberrations 756, 165\u2013169. http:\/\/dx.doi.org\/10.1016\/j.mrgentox.2013.04.007.","DOI":"10.1016\/j.mrgentox.2013.04.007"},{"key":"10.1016\/j.arr.2024.102227_bib47","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1667\/RR3323.1","article-title":"Stability of chromosome aberrations in the blood lymphocytes of astronauts measured after space flight by FISH chromosome painting","volume":"164","author":"George","year":"2005","journal-title":"rare"},{"key":"10.1016\/j.arr.2024.102227_bib48","doi-asserted-by":"crossref","unstructured":"Greco, O., Durante, M., Gialanella, G., Grossi, G., Pugliese, M., Scampoli, P., Snigiryova, G., Obe, G., 2003. Biological dosimetry in Russian and Italian astronauts. Advances in Space Research, Space Life Sciences: Biodosimetry, Biomarkers and Late Stochastic Effects of Space Radiation 31, 1495\u20131503.","DOI":"10.1016\/S0273-1177(03)00087-5"},{"key":"10.1016\/j.arr.2024.102227_bib49","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and aging-related diseases: from molecular mechanisms to interventions and treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Sig Transduct. Target Ther."},{"key":"10.1016\/j.arr.2024.102227_bib50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/japplphysiol.01098.2018","article-title":"Daily heat treatment maintains mitochondrial function and attenuates atrophy in human skeletal muscle subjected to immobilization","volume":"127","author":"Hafen","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib51","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molcel.2012.10.016","article-title":"Genome-wide methylation profiles reveal quantitative views of human aging rates","volume":"49","author":"Hannum","year":"2013","journal-title":"Mol. Cell"},{"key":"10.1016\/j.arr.2024.102227_bib52","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.1111\/1462-2920.14358","article-title":"The influence of bioregenerative life-support system dietary structure and lifestyle on the gut microbiota: a 105-day ground-based space simulation in Lunar Palace 1","volume":"20","author":"Hao","year":"2018","journal-title":"Environ. Microbiol"},{"key":"10.1016\/j.arr.2024.102227_bib53","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.arr.2024.102227_bib54","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/803083","article-title":"How fast is recovery of impaired glucose tolerance after 21-day bed rest (NUC Study) in healthy adults?","volume":"2014","author":"Heer","year":"2014","journal-title":"Sci. World J."},{"key":"10.1016\/j.arr.2024.102227_bib55","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0072824","article-title":"Predictors and consequences of global DNA methylation in cord blood and at three years","volume":"8","author":"Herbstman","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.arr.2024.102227_bib56","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of cellular senescence","volume":"28","author":"Hernandez-Segura","year":"2018","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.arr.2024.102227_bib57","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1038\/s41467-019-12293-4","article-title":"Ageing affects DNA methylation drift and transcriptional cell-to-cell variability in mouse muscle stem cells","volume":"10","author":"Hernando-Herraez","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.arr.2024.102227_bib58","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-019-0101-y","article-title":"The proteostasis network and its decline in ageing","volume":"20","author":"Hipp","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.arr.2024.102227_bib59","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1056\/NEJMra0804615","article-title":"DNA damage, aging, and cancer","volume":"361","author":"Hoeijmakers","year":"2009","journal-title":"N. Engl. J. Med"},{"key":"10.1016\/j.arr.2024.102227_bib60","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1128\/aem.31.3.359-375.1976","article-title":"Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress","volume":"31","author":"Holdeman","year":"1976","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.arr.2024.102227_bib61","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":"10.1016\/j.arr.2024.102227_bib62","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":"10.1016\/j.arr.2024.102227_bib63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Sig Transduct. Target Ther."},{"key":"10.1016\/j.arr.2024.102227_bib64","doi-asserted-by":"crossref","first-page":"H628","DOI":"10.1152\/ajpheart.00802.2015","article-title":"Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6-mo spaceflight in male and female astronauts","volume":"310","author":"Hughson","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib65","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1152\/japplphysiol.00521.2016","article-title":"Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise","volume":"122","author":"Irimia","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib66","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/cmi.2017.84","article-title":"Role of programmed cell death 4 in diseases: a double-edged sword","volume":"14","author":"Jiang","year":"2017","journal-title":"Cell Mol. Immunol."},{"key":"10.1016\/j.arr.2024.102227_bib67","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.psyneuen.2013.11.004","article-title":"Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators","volume":"40","author":"Kaliman","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.arr.2024.102227_bib68","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.bbi.2004.12.006","article-title":"Changes in monocyte functions of astronauts","volume":"19","author":"Kaur","year":"2005","journal-title":"Brain, Behav.\u00a0Immun."},{"key":"10.1016\/j.arr.2024.102227_bib69","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.cyto.2012.04.032","article-title":"21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog","volume":"59","author":"Kelsen","year":"2012","journal-title":"Cytokine"},{"key":"10.1016\/j.arr.2024.102227_bib70","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature08980","article-title":"The genetics of ageing","volume":"464","author":"Kenyon","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.arr.2024.102227_bib71","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.arr.2010.02.001","article-title":"Protein homeostasis and aging: The importance of exquisite quality control","volume":"10","author":"Koga","year":"2011","journal-title":"Ageing Res. Rev.\u00a0Longev. Consort."},{"key":"10.1016\/j.arr.2024.102227_bib72","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.725748","article-title":"Alterations in saliva and plasma cytokine concentrations during long-duration spaceflight","volume":"12","author":"Krieger","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.arr.2024.102227_bib73","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1101\/gad.1971610","article-title":"The essence of senescence","volume":"24","author":"Kuilman","year":"2010","journal-title":"Genes Dev."},{"key":"10.1016\/j.arr.2024.102227_bib74","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1097\/00001756-200005150-00042","article-title":"Functional brain mapping of the relaxation response and meditation","volume":"11","author":"Lazar","year":"2000","journal-title":"Neuroreport"},{"key":"10.1016\/j.arr.2024.102227_bib75","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological functions of autophagy genes: a disease perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib76","doi-asserted-by":"crossref","first-page":"573","DOI":"10.18632\/aging.101414","article-title":"An epigenetic biomarker of aging for lifespan and healthspan","volume":"10","author":"Levine","year":"2018","journal-title":"Aging"},{"key":"10.1016\/j.arr.2024.102227_bib77","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/nmo.12822","article-title":"Gut microbes in correlation with mood: case study in a closed experimental human life support system","volume":"28","author":"Li","year":"2016","journal-title":"Neurogastroenterol. Motil."},{"key":"10.1016\/j.arr.2024.102227_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0182970","article-title":"Effects of short-term dry immersion on bone remodeling markers, insulin and adipokines","volume":"12","author":"Linossier","year":"2017","journal-title":"PLOS ONE"},{"key":"10.1016\/j.arr.2024.102227_bib79","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1080\/19490976.2019.1710091","article-title":"Effects of spaceflight on the composition and function of the human gut microbiota","volume":"11","author":"Liu","year":"2020","journal-title":"Gut Microbes"},{"key":"10.1016\/j.arr.2024.102227_bib80","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"L\u00f3pez-Ot\u00edn","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib81","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The Hallmarks of Aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.arr.2024.102227_bib82","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nature10760","article-title":"The DNA damage response and cancer therapy","volume":"481","author":"Lord","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.arr.2024.102227_bib83","doi-asserted-by":"crossref","first-page":"7S","DOI":"10.1097\/PRS.0000000000007616","article-title":"Twins, telomeres, and aging\u2014in space!","volume":"147","author":"Luxton","year":"2021","journal-title":"Plast. Reconstr. Surg."},{"key":"10.1016\/j.arr.2024.102227_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108435","article-title":"Temporal telomere and DNA damage responses in the space radiation environment","volume":"33","author":"Luxton","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.arr.2024.102227_bib85","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108457","article-title":"Telomere length dynamics and DNA damage responses associated with long-duration spaceflight","volume":"33","author":"Luxton","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.arr.2024.102227_bib86","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40168-020-00959-x","article-title":"Microbiome dynamics during the HI-SEAS IV mission, and implications for future crewed missions beyond Earth","volume":"9","author":"Mahnert","year":"2021","journal-title":"Microbiome"},{"key":"10.1016\/j.arr.2024.102227_bib87","doi-asserted-by":"crossref","first-page":"116","DOI":"10.32607\/20758251-2013-5-3-116-125","article-title":"Metagenomic analysis of the dynamic changes in the gut microbiome of the participants of the MARS-500 experiment, simulating long term space flight","volume":"5","author":"Mardanov","year":"2013","journal-title":"Acta Nat."},{"key":"10.1016\/j.arr.2024.102227_bib88","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.4161\/epi.6.9.16401","article-title":"Evidence for age-related and individual-specific changes in DNA methylation profile of mononuclear cells during early immune development in humans","volume":"6","author":"Martino","year":"2011","journal-title":"Epigenetics"},{"key":"10.1016\/j.arr.2024.102227_bib89","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1152\/jappl.1999.87.3.1207","article-title":"Spaceflight suppresses exercise-induced release of bioassayable growth hormone","volume":"87","author":"McCall","year":"1999","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib90","first-page":"491","article-title":"Alteration in human mononuclear leucocytes following space flight","volume":"76","author":"Meehan","year":"1992","journal-title":"Immunology"},{"key":"10.1016\/j.arr.2024.102227_bib91","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cyto.2012.09.019","article-title":"Reactivation of latent viruses is associated with increased plasma cytokines in astronauts","volume":"61","author":"Mehta","year":"2013","journal-title":"Cytokine"},{"key":"10.1016\/j.arr.2024.102227_bib92","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.arr.2024.102227_bib93","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.immuni.2020.11.005","article-title":"Comprehensive profiling of an aging immune system reveals clonal GZMK+ CD8+ T cells as conserved hallmark of inflammaging","volume":"54","author":"Mogilenko","year":"2021","journal-title":"Immunity"},{"key":"10.1016\/j.arr.2024.102227_bib94","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacol"},{"key":"10.1016\/j.arr.2024.102227_bib95","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2021.659179","article-title":"Investigation of spaceflight induced changes to astronaut microbiomes","volume":"12","author":"Morrison","year":"2021","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.arr.2024.102227_bib96","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.arr.2012.02.001","article-title":"The role of DNA damage and repair in aging through the prism of Koch-like criteria","volume":"12","author":"Moskalev","year":"2013","journal-title":"Ageing Res Rev."},{"key":"10.1016\/j.arr.2024.102227_bib97","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.arr.2013.01.003","article-title":"A systematic review of leukocyte telomere length and age in adults","volume":"12","author":"M\u00fcezzinler","year":"2013","journal-title":"Ageing Res Rev."},{"key":"10.1016\/j.arr.2024.102227_bib98","unstructured":"NASA Lunar Programs: Improved Mission Guidance Needed as Artemis Complexity Grows | U.S. GAO [WWW Document], n.d. URL \u3008https:\/\/www.gao.gov\/products\/gao-22-105323\u3009 (accessed 6.30.23)."},{"key":"10.1016\/j.arr.2024.102227_bib99","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108406","article-title":"A longitudinal epigenetic aging and leukocyte analysis of simulated space travel: the Mars-500 Mission","volume":"33","author":"Nwanaji-Enwerem","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.arr.2024.102227_bib100","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/mus.20611","article-title":"Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest","volume":"34","author":"Ogawa","year":"2006","journal-title":"Muscle Nerve"},{"key":"10.1016\/j.arr.2024.102227_bib101","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202201005RR","article-title":"Impact of 10-day bed rest on serum levels of irisin and markers of musculoskeletal metabolism","volume":"37","author":"Oranger","year":"2023","journal-title":"FASEB J."},{"key":"10.1016\/j.arr.2024.102227_bib102","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41526-020-00124-6","article-title":"Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars","volume":"6","author":"Patel","year":"2020","journal-title":"NPJ Microgravity"},{"key":"10.1016\/j.arr.2024.102227_bib103","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1001\/archinte.166.11.1218","article-title":"Effects of a randomized controlled trial of transcendental meditation on components of the metabolic syndrome in subjects with coronary heart disease","volume":"166","author":"Paul-Labrador","year":"2006","journal-title":"Arch. Intern Med"},{"key":"10.1016\/j.arr.2024.102227_bib104","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.3390\/jcm10163700","article-title":"Longer leukocytes telomere length predicts a significant survival advantage in the elderly TRELONG cohort, with short physical performance battery score and years of education as main determinants for telomere elongation","volume":"10","author":"Pavanello","year":"2021","journal-title":"J. Clin. Med"},{"key":"10.1016\/j.arr.2024.102227_bib105","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph16173074","article-title":"Exploring epigenetic age in response to intensive relaxing training: a pilot study to slow down biological age","volume":"16","author":"Pavanello","year":"2019","journal-title":"Int J. Environ. Res Public Health"},{"key":"10.1016\/j.arr.2024.102227_bib106","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13148-016-0228-z","article-title":"Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort","volume":"8","author":"Perna","year":"2016","journal-title":"Clin. Epigenetics"},{"key":"10.1016\/j.arr.2024.102227_bib107","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12979-020-00213-w","article-title":"Gut microbiota as the key controllers of \u201chealthy\u201d aging of elderly people","volume":"18","author":"Ragonnaud","year":"2021","journal-title":"Immun. Ageing"},{"key":"10.1016\/j.arr.2024.102227_bib108","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1152\/japplphysiol.00444.2010","article-title":"Forty-eight hours of unloading and 24h of reloading lead to changes in global gene expression patterns related to ubiquitination and oxidative stress in humans","volume":"109","author":"Reich","year":"2010","journal-title":"J. Appl. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib109","unstructured":"Research, N.R.C. (US) and I. of M. (US) C. on the B. and B.A. of S.C., 2002. Project Overview and Definitions, in: Stem Cells and the Future of Regenerative Medicine. National Academies Press (US)."},{"key":"10.1016\/j.arr.2024.102227_bib110","doi-asserted-by":"crossref","DOI":"10.1038\/srep17027","article-title":"Vibration mechanosignals superimposed to resistive exercise result in baseline skeletal muscle transcriptome profiles following chronic disuse in bed rest","volume":"5","author":"Salanova","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2024.102227_bib111","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.arr.2007.09.002","article-title":"Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging","volume":"7","author":"Salminen","year":"2008","journal-title":"Ageing Res Rev."},{"key":"10.1016\/j.arr.2024.102227_bib112","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1113\/JP275605","article-title":"PlanHab*: hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone","volume":"596","author":"Salvadego","year":"2018","journal-title":"J. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib113","doi-asserted-by":"crossref","first-page":"362","DOI":"10.2174\/1574888X15666200213105155","article-title":"Stem cell aging in lifespan and disease: a state-of-the-art review","volume":"15","author":"Sameri","year":"2020","journal-title":"Curr. Stem Cell Res Ther."},{"key":"10.1016\/j.arr.2024.102227_bib114","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3390\/genes8120398","article-title":"The mitochondrial basis of aging and age-related disorders","volume":"8","author":"Srivastava","year":"2017","journal-title":"Genes (Basel)"},{"key":"10.1016\/j.arr.2024.102227_bib115","first-page":"E155","article-title":"Endocrine relationships during human spaceflight","volume":"276","author":"Stein","year":"1999","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib116","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/jlb.65.2.179","article-title":"Leukocyte subsets and neutrophil function after short-term spaceflight","volume":"65","author":"Stowe","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.arr.2024.102227_bib117","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1569-2574(08)60008-8","article-title":"Hormonal changes in humans during spaceflight","author":"Strollo","year":"1999","journal-title":"Adv. Space Biol. Med 7"},{"key":"10.1016\/j.arr.2024.102227_bib118","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s40618-018-0861-9","article-title":"Body composition and metabolic changes during a 520-day mission simulation to Mars","volume":"41","author":"Strollo","year":"2018","journal-title":"J. Endocrinol. Invest"},{"key":"10.1016\/j.arr.2024.102227_bib119","first-page":"1146","article-title":"Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort","volume":"45","author":"Tan","year":"2016","journal-title":"Int J. Epidemiol."},{"key":"10.1016\/j.arr.2024.102227_bib120","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/20009666.2016.1270806","article-title":"Effect of heartfulness meditation on burnout, emotional wellness, and telomere length in health care professionals","volume":"7","author":"Thimmapuram","year":"2017","journal-title":"J. Community Hosp. Intern Med Perspect."},{"key":"10.1016\/j.arr.2024.102227_bib121","doi-asserted-by":"crossref","first-page":"G602","DOI":"10.1152\/ajpgi.00230.2019","article-title":"Dysbiosis: from fiction to function","volume":"317","author":"Tiffany","year":"2019","journal-title":"Am. J. Physiol. -Gastrointest. Liver Physiol."},{"key":"10.1016\/j.arr.2024.102227_bib122","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40168-017-0256-8","article-title":"Temporal dynamics of the gut microbiota in people sharing a confined environment, a 520-day ground-based space simulation, MARS500","volume":"5","author":"Turroni","year":"2017","journal-title":"Microbiome"},{"key":"10.1016\/j.arr.2024.102227_bib123","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40168-020-00830-z","article-title":"The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation","volume":"8","author":"Urbaniak","year":"2020","journal-title":"Microbiome"},{"key":"10.1016\/j.arr.2024.102227_bib124","unstructured":"Vernikos, J., Hosie, R., 2004. The G-Connection: Harness Gravity and Reverse Aging. Joan Vernikos."},{"key":"10.1016\/j.arr.2024.102227_bib125","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1159\/000252852","article-title":"Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review","volume":"56","author":"Vernikos","year":"2010","journal-title":"Gerontology"},{"key":"10.1016\/j.arr.2024.102227_bib126","doi-asserted-by":"crossref","first-page":"9911","DOI":"10.1038\/s41598-019-46303-8","article-title":"Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome","volume":"9","author":"Voorhies","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.arr.2024.102227_bib127","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/cen.12535","article-title":"Effects of 60-day head-down bed rest on osteocalcin, glycolipid metabolism and their association with or without resistance training","volume":"81","author":"Yang","year":"2014","journal-title":"Clin. Endocrinol."},{"key":"10.1016\/j.arr.2024.102227_bib128","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.bbi.2014.03.018","article-title":"520-d Isolation and confinement simulating a flight to Mars reveals heightened immune responses and alterations of leukocyte phenotype","volume":"40","author":"Yi","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.arr.2024.102227_bib129","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.fsigen.2015.05.001","article-title":"Development of a forensically useful age prediction method based on DNA methylation analysis","volume":"17","author":"Zbie\u0107-Piekarska","year":"2015","journal-title":"Forensic Sci. Int Genet"},{"key":"10.1016\/j.arr.2024.102227_bib130","series-title":"Epigenetics in Allergy and Autoimmunity, Advances in Experimental Medicine and Biology","first-page":"3","article-title":"Epigenetics in Health and Disease","author":"Zhang","year":"2020"}],"container-title":["Ageing Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372400045X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S156816372400045X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T21:43:37Z","timestamp":1744494217000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S156816372400045X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":130,"alternative-id":["S156816372400045X"],"URL":"https:\/\/doi.org\/10.1016\/j.arr.2024.102227","relation":{},"ISSN":["1568-1637"],"issn-type":[{"value":"1568-1637","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cosmic chronometers: Is spaceflight a catalyst for biological ageing?","name":"articletitle","label":"Article Title"},{"value":"Ageing Research Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.arr.2024.102227","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"102227"}}