{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:32:12Z","timestamp":1793431932616,"version":"4.5.0"},"reference-count":109,"publisher":"Radiation Research Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2022,7,14]]},"abstract":"<jats:p>The hematopoietic system is highly sensitive to stress from both aging and radiation exposure, and the hematopoietic acute radiation syndrome (H-ARS) should be modeled in the geriatric context separately from young for development of age-appropriate medical countermeasures (MCMs). Here we developed aging murine H-ARS models, defining radiation dose response relationships (DRRs) in 12-month-old middle-aged and 24-month-old geriatric male and female C57BL\/6J mice, and characterized diverse factors affecting geriatric MCM testing. Groups of approximately 20 mice were exposed to \u223c10 different doses of radiation to establish radiation DRRs for estimation of the LD50\/30. Radioresistance increased with age and diverged dramatically between sexes. The LD50\/30 in young adult mice averaged 853 cGy and was similar between sexes, but increased in middle age to 1,005 cGy in males and 920 cGy in females, with further sex divergence in geriatric mice to 1,008 cGy in males but 842 cGy in females. Correspondingly, neutrophils, platelets, and functional hematopoietic progenitor cells were all increased with age and rebounded faster after irradiation. These effects were higher in aged males, and neutrophil dysfunction was observed in aged females. Upstream of blood production, hematopoietic stem cell (HSC) markers associated with age and myeloid bias (CD61 and CD150) were higher in geriatric males vs. females, and sex-divergent gene signatures were found in HSCs relating to cholesterol metabolism, interferon signaling, and GIMAP family members. Fluid intake per gram body weight decreased with age in males, and decreased after irradiation in all mice. Geriatric mice of substrain C57BL\/6JN sourced from the National Institute on Aging were significantly more radiosensitive than C57BL\/6J mice from Jackson Labs aged at our institution, indicating mouse source and substrain should be considered in geriatric radiation studies. This work highlights the importance of sex, vendor, and other considerations in studies relating to hematopoiesis and aging, identifies novel sex-specific functional and molecular changes in aging hematopoietic cells at steady state and after irradiation, and presents well-characterized aging mouse models poised for MCM efficacy testing for treatment of acute radiation effects in the elderly.<\/jats:p>","DOI":"10.1667\/rade-22-00071.1","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T17:35:04Z","timestamp":1657820104000},"page":"221-242","source":"Crossref","is-referenced-by-count":36,"title":["Age and Sex Divergence in Hematopoietic Radiosensitivity in Aged Mouse Models of the Hematopoietic Acute Radiation Syndrome"],"prefix":"10.1667","volume":"198","author":[{"given":"Andrea M.","family":"Patterson","sequence":"first","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasidhar","family":"Vemula","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Artur","family":"Plett","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol H.","family":"Sampson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Lin","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendran","family":"Sellamuthu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry P.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"DesRosiers","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis M.","family":"Pelus","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George N.","family":"Cox","sequence":"additional","affiliation":[{"name":"Bolder Biotechnology, Inc., Boulder, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"MacVittie","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie M.","family":"Orschell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"30","doi-asserted-by":"crossref","unstructured":"A Dobin, CA Davis, F Schlesinger, et al.  \"Bioinformatics.\"  29, \"STAR: ultrafast universal RNA-seq aligner.\" 15 (2013)","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"84","doi-asserted-by":"crossref","unstructured":"AL DiCarlo, ZP Horta, JT Aldrich, et al.  \"Radiat Res.\"  192, \"Use of growth factors and other cytokines for treatment of injuries during a radiation public health emergency.\" 99 (2019)","DOI":"10.1667\/RR15363.1"},{"key":"1","doi-asserted-by":"crossref","unstructured":"CN Coleman, WF Blakely, JR Fike, et al.  \"Radiat Res.\"  159, \"Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001.\" 812 (2003)","DOI":"10.1667\/RR3021"},{"key":"2","doi-asserted-by":"crossref","unstructured":"N Dainiak, JK Waselenko, JO Armitage, et al.  \"Hematology (Am Soc Hematol Educ Program).\"  \"The hematologist and radiation casualties.\" 473 (2003)","DOI":"10.1182\/asheducation-2003.1.473"},{"key":"3","unstructured":"\"Sect.\"  67, \"New drug and biological drug products; Evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. 21 CFR parts 314 and 601,\" (2002)"},{"key":"5","doi-asserted-by":"crossref","unstructured":"PA Plett, CH Sampson, HL Chua, et al.  \"Health Physics.\"  109, \"The H-ARS dose response relationship (DRR): Validation and variables.\" 391 (2015)","DOI":"10.1097\/HP.0000000000000354"},{"key":"7","doi-asserted-by":"crossref","unstructured":"AM Patterson, R Sellamuthu, PA Plett, et al.  \"Radiat Res.\"  195, \"Establishing pediatric mouse models of the hematopoietic acute radiation syndrome and the delayed effects of acute radiation exposure.\" 307 (2021)","DOI":"10.1667\/RADE-20-00259.1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"HL Chua, PA Plett, CH Sampson, et al.  \"Health Physics.\"  106, \"Survival efficacy of the pegylated G-CSF Maxy-G34 and Neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors.\" 21 (2014)","DOI":"10.1097\/HP.0b013e3182a4df10"},{"key":"10","doi-asserted-by":"crossref","unstructured":"PA Plett, HL Chua, CH Sampson, et al.  \"Health Physics.\"  106, \"PEGylated G-CSF (BBT-015), GM-CSF (BBT-007), and IL-11 (BBT-059) analogs enhance survival and hematopoietic cell recovery in a mouse model of the Hematopoietic Syndrome of the Acute Radiation Syndrome.\" 7 (2014)","DOI":"10.1097\/HP.0b013e3182a4dd4e"},{"key":"13","unstructured":"\"Geriatric Information in Human Prescription Drug and Biological Product Labeling: Guidance for Industry.\"  2020"},{"key":"14","doi-asserted-by":"crossref","unstructured":"E Rudnicka, P Napierala, A Podfigurna, et al.  \"Maturitas.\"  139, \"The World Health Organization (WHO) approach to healthy ageing.\" 6 (2020)","DOI":"10.1016\/j.maturitas.2020.05.018"},{"key":"15","doi-asserted-by":"crossref","unstructured":"SJ Morrison, AM Wandycz, K Akashi, et al.  \"Nat Med.\"  2, \"The aging of hematopoietic stem cells.\" 1011 (1996)","DOI":"10.1038\/nm0996-1011"},{"key":"16","doi-asserted-by":"crossref","unstructured":"DJ Rossi, D Bryder, JM Zahn, et al.  \"Proc Natl Acad Sci U S A.\"  102, \"Cell intrinsic alterations underlie hematopoietic stem cell aging.\" 9194 (2005)","DOI":"10.1073\/pnas.0503280102"},{"key":"17","doi-asserted-by":"crossref","unstructured":"SM Chambers, CA Shaw, C Gatza, et al.  \"PLoS Biol.\"  5, \"Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation.\" e201 (2007)","DOI":"10.1371\/journal.pbio.0050201"},{"key":"18","doi-asserted-by":"crossref","unstructured":"WW Pang, EA Price, D Sahoo, et al.  \"Proc Natl Acad Sci U S A.\"  108, \"Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age.\" 20012 (2011)","DOI":"10.1073\/pnas.1116110108"},{"key":"19","doi-asserted-by":"crossref","unstructured":"J. Nikolich-Zugich,  \"Nat Immunol.\"  19, \"The twilight of immunity: emerging concepts in aging of the immune system.\" 10 (2018)","DOI":"10.1038\/s41590-018-0205-0"},{"key":"20","doi-asserted-by":"crossref","unstructured":"H Leins, M Mulaw, K Eiwen, et al.  \"Blood.\"  132, \"Aged murine hematopoietic stem cells drive aging-associated immune remodeling.\" 565 (2018)","DOI":"10.1182\/blood-2018-02-831065"},{"key":"21","doi-asserted-by":"crossref","unstructured":"X Li, X Zeng, Y Xu, et al.  \"J Hematol Oncol.\"  13, \"Mechanisms and rejuvenation strategies for aged hematopoietic stem cells.\" 31 (2020)","DOI":"10.1186\/s13045-020-00864-8"},{"key":"22","doi-asserted-by":"crossref","unstructured":"SL. Klein,  \"Neurosci Biobehav Rev.\"  24, \"The effects of hormones on sex differences in infection: from genes to behavior.\" 627 (2000)","DOI":"10.1016\/S0149-7634(00)00027-0"},{"key":"23","doi-asserted-by":"crossref","unstructured":"CW Roberts, W Walker, J Alexander,  \"Clin Microbiol Rev.\"  14, \"Sex-associated hormones and immunity to protozoan parasites.\" 476 (2001)","DOI":"10.1128\/CMR.14.3.476-488.2001"},{"key":"24","doi-asserted-by":"crossref","unstructured":"CC. Whitacre,  \"Nat Immunol.\"  2, \"Sex differences in autoimmune disease.\" 777 (2001)","DOI":"10.1038\/ni0901-777"},{"key":"25","unstructured":"\"Physiological Data Summary \u2013 Aged C57BL\/6J (000664).\""},{"key":"26","doi-asserted-by":"crossref","unstructured":"SC Grubb, TP Maddatu, CJ Bult, et al.  \"Nucleic Acids Res.\"  37, \"Mouse phenome database.\" D720 (2009)","DOI":"10.1093\/nar\/gkn778"},{"key":"27","doi-asserted-by":"crossref","unstructured":"HL Chua, PA Plett, A Fisher, et al.  \"Health Physics.\"  116, \"Lifelong residual bone marrow damage in murine survivors of the hematopoietic acute radiation syndrome (H-ARS): a compilation of studies comprising the Indiana University experience.\" 546 (2019)","DOI":"10.1097\/HP.0000000000000950"},{"key":"29","doi-asserted-by":"crossref","unstructured":"S Doulatov, F Notta, E Laurenti, et al.  \"Cell Stem Cell.\"  10, \"Hematopoiesis: a human perspective.\" 120 (2012)","DOI":"10.1016\/j.stem.2012.01.006"},{"key":"31","doi-asserted-by":"crossref","unstructured":"MR Breese  and Y Liu  \"Bioinformatics.\"  29, \"NGSUtils: a software suite for analyzing and manipulating next-generation sequencing datasets.\" 494 (2013)","DOI":"10.1093\/bioinformatics\/bts731"},{"key":"38","doi-asserted-by":"crossref","unstructured":"J Garrett, CH Sampson, PA Plett, et al.  \"Radiat Res.\"  191, \"Characterization and etiology of swollen muzzles in irradiated mice.\" 31 (2018)","DOI":"10.1667\/RR14724.1"},{"key":"39","doi-asserted-by":"crossref","unstructured":"J Spalding  and T Trujillo  \"Radiat Res.\"  16, \"Radiosensitivity of mice as a function of age.\" 125 (1962)","DOI":"10.2307\/3571191"},{"key":"41","doi-asserted-by":"crossref","unstructured":"H Fuchs, C Gau, W Hans, et al.  \"Mamm Genome.\"  24, \"Long-term experiment to study the development, interaction, and influencing factors of DEXA parameters.\" 376 (2013)","DOI":"10.1007\/s00335-013-9477-8"},{"key":"42","doi-asserted-by":"crossref","unstructured":"T Wu, PA Plett, HL Chua, et al.  \"Health Phys.\"  119, \"Immune reconstitution and thymic involution in the acute and delayed hematopoietic radiation syndromes.\" 647 (2020)","DOI":"10.1097\/HP.0000000000001352"},{"key":"44","doi-asserted-by":"crossref","unstructured":"R Gazit, PK Mandal, W Ebina, et al.  \"J Exp Med.\"  211, \"Fgd5 identifies hematopoietic stem cells in the murine bone marrow.\" 1315 (2014)","DOI":"10.1084\/jem.20130428"},{"key":"45","doi-asserted-by":"crossref","unstructured":"L Zhang, R Mack, P Breslin, et al.  \"J Hematol Oncol.\"  13, \"Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.\" 157 (2020)","DOI":"10.1186\/s13045-020-00994-z"},{"key":"46","doi-asserted-by":"crossref","unstructured":"I Beerman, D Bhattacharya, S Zandi, et al.  \"Proc Natl Acad Sci U S A.\"  107, \"Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion.\" 5465 (2010)","DOI":"10.1073\/pnas.1000834107"},{"key":"47","doi-asserted-by":"crossref","unstructured":"M Mann, A Mehta, CG de Boer, et al.  \"Cell Rep.\"  25, \"Heterogeneous responses of hematopoietic stem cells to inflammatory stimuli are altered with age.\" 2992 (2018)","DOI":"10.1016\/j.celrep.2018.11.056"},{"key":"48","doi-asserted-by":"crossref","unstructured":"JY Shin, W Hu, M Naramura, et al.  \"J Exp Med.\"  211, \"High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias.\" 217 (2014)","DOI":"10.1084\/jem.20131128"},{"key":"49","doi-asserted-by":"crossref","unstructured":"C Franceschi, M Bonafe, S Valensin, et al.  \"Ann N Y Acad Sci.\"  908, \"Inflamm-aging. An evolutionary perspective on immunosenescence.\" 244 (2000)","DOI":"10.1111\/j.1749-6632.2000.tb06651.x"},{"key":"50","doi-asserted-by":"crossref","unstructured":"A Flohr Svendsen, D Yang, K Kim, et al.  \"Blood.\"  138, \"A comprehensive transcriptome signature of murine hematopoietic stem cell aging.\" 439 (2021)","DOI":"10.1182\/blood.2020009729"},{"key":"51","doi-asserted-by":"crossref","unstructured":"V Janzen, R Forkert, HE Fleming, et al.  \"Nature.\"  443, \"Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a.\" 421 (2006)","DOI":"10.1038\/nature05159"},{"key":"52","doi-asserted-by":"crossref","unstructured":"EM Pietras, MR Warr, E Passegue,  \"J Cell Biol.\"  195, \"Cell cycle regulation in hematopoietic stem cells.\" 709 (2011)","DOI":"10.1083\/jcb.201102131"},{"key":"53","doi-asserted-by":"crossref","unstructured":"D Sun, M Luo, M Jeong, et al.  \"Cell Stem Cell.\"  14, \"Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal.\" 673 (2014)","DOI":"10.1016\/j.stem.2014.03.002"},{"key":"54","doi-asserted-by":"crossref","unstructured":"MS Kowalczyk, I Tirosh, D Heckl, et al.  \"Genome Res.\"  25, \"Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells.\" 1860 (2015)","DOI":"10.1101\/gr.192237.115"},{"key":"55","doi-asserted-by":"crossref","unstructured":"MA Limoges, M Cloutier, M Nandi, et al.  \"Front Immunol.\"  12, \"The GIMAP Family Proteins: An Incomplete Puzzle.\" 679739 (2021)","DOI":"10.3389\/fimmu.2021.679739"},{"key":"56","doi-asserted-by":"crossref","unstructured":"Y Chen, M Yu, X Dai, et al.  \"J Exp Med.\"  208, \"Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells.\" 923 (2011)","DOI":"10.1084\/jem.20101192"},{"key":"57","doi-asserted-by":"crossref","unstructured":"H. Oguro,  \"Front Endocrinol (Lausanne).\"  10, \"The Roles of cholesterol and its metabolites in normal and malignant hematopoiesis.\" 204 (2019)","DOI":"10.3389\/fendo.2019.00204"},{"key":"58","doi-asserted-by":"crossref","unstructured":"AJ Murphy, M Akhtari, S Tolani, et al.  \"The Journal of clinical investigation.\"  121, \"ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice.\" 4138 (2011)","DOI":"10.1172\/JCI57559"},{"key":"60","doi-asserted-by":"crossref","unstructured":"DV Faller, SA Castaneda, D Zhou, et al.  \"Blood Cells, Mol Dis.\"  63, \"An oral HemokineTM, \u03b1-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo.\" 1 (2017)","DOI":"10.1016\/j.bcmd.2016.10.021"},{"key":"62","doi-asserted-by":"crossref","unstructured":"A Patterson, T Wu, H Chua, et al.  \"Radiat Res.\"  \"Optimizing and Profiling Prostaglandin E2 as a Medical Countermeasure for the Hematopoietic Acute Radiation Syndrome.\" (2020)","DOI":"10.1667\/RADE-20-00181.1"},{"key":"63","doi-asserted-by":"crossref","unstructured":"JF Spalding  and TT Trujillo  \"Radiat Res.\"  16, \"Radiosensitivity of mice as a function of age.\" 125 (1962)","DOI":"10.2307\/3571191"},{"key":"64","unstructured":"AA Horland, L McMorrow, SR Wolman,  \"Exp Hematol.\"  8, \"Growth of granulopoietic bone marrow cells of RF mice.\" 1024 (1980)"},{"key":"65","doi-asserted-by":"crossref","unstructured":"W. Lane-Petter,  \"Proc R Soc Med.\"  55, \"Provision of pathogen-free animals.\" 253 (1962)","DOI":"10.1177\/003591576205500402"},{"key":"66","doi-asserted-by":"crossref","unstructured":"SN. Austad,  \"Gend Med.\"  3, \"Why women live longer than men: sex differences in longevity.\" 79 (2006)","DOI":"10.1016\/S1550-8579(06)80198-1"},{"key":"67","unstructured":"GEP Box  and NR Draper  \"Empirical Model-Building and Response Surface.\"  (1987)"},{"key":"68","doi-asserted-by":"crossref","unstructured":"C Pettan-Brewer  and PM Treuting  \"Pathobiol Aging Age Relat Dis.\"  1, \"Practical pathology of aging mice.\" (2011)","DOI":"10.3402\/pba.v1i0.7202"},{"key":"69","unstructured":"S. Edie,  \"The Jax Blog [Internet]. The Jackson Laboratory 2020. [cited 2020].\""},{"key":"70","doi-asserted-by":"crossref","unstructured":"J Hong, RE Stubbins, RR Smith, et al.  \"Nutr J.\"  8, \"Differential susceptibility to obesity between male, female and ovariectomized female mice.\" 11 (2009)","DOI":"10.1186\/1475-2891-8-11"},{"key":"71","doi-asserted-by":"crossref","unstructured":"JB. Prins,  \"Best Pract Res Clin Endocrinol Metab.\"  16, \"Adipose tissue as an endocrine organ.\" 639 (2002)","DOI":"10.1053\/beem.2002.0222"},{"key":"72","doi-asserted-by":"crossref","unstructured":"PM Treuting, JM Snyder, Y Ikeno, et al.  \"Vet Pathol.\"  53, \"The vital role of pathology in improving reproducibility and translational relevance of aging studies in rodents.\" 244 (2016)","DOI":"10.1177\/0300985815620629"},{"key":"73","doi-asserted-by":"crossref","unstructured":"HD Fulenwider, MT Robins, MA Caruso, et al.  \"Front Behav Neurosci.\"  2021, \"Social housing leads to increased ethanol intake in male mice housed in environmentally enriched cages.\" 15","DOI":"10.3389\/fnbeh.2021.695409"},{"key":"74","doi-asserted-by":"crossref","unstructured":"PL Van Loo, HA Van de Weerd, LF Van Zutphen, et al.  \"Lab Anim.\"  38, \"Preference for social contact versus environmental enrichment in male laboratory mice.\" 178 (2004)","DOI":"10.1258\/002367704322968867"},{"key":"75","doi-asserted-by":"crossref","unstructured":"TM Keane, L Goodstadt, P Danecek, et al.  \"Nature.\"  477, \"Mouse genomic variation and its effect on phenotypes and gene regulation.\" 289 (2011)","DOI":"10.1038\/nature10413"},{"key":"76","unstructured":"MM Simon, S Greenaway, JK White, et al.  \"Genome Biol.\"  14, \"A comparative phenotypic and genomic analysis of C57BL\/6J and C57BL\/6N mouse strains.\" R82 (2013)"},{"key":"77","doi-asserted-by":"crossref","unstructured":"DI Bunin, J Bakke, CE Green, et al.  \"Int J Radiat Biol.\"  96, \"Romiplostim (Nplate\u00ae) as an effective radiation countermeasure to improve survival and platelet recovery in mice.\" 145 (2020)","DOI":"10.1080\/09553002.2019.1605465"},{"key":"78","doi-asserted-by":"crossref","unstructured":"A Grover, A Sanjuan-Pla, S Thongjuea, et al.  \"Nat Commun.\"  7, \"Single-cell RNA sequencing reveals molecular and functional platelet bias of aged haematopoietic stem cells.\" 11075 (2016)","DOI":"10.1038\/ncomms11075"},{"key":"79","doi-asserted-by":"crossref","unstructured":"A Rundberg Nilsson, S Soneji, S Adolfsson, et al.  \"PLoS One.\"  11, \"Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic\/ erythroid bias.\" e0158369 (2016)","DOI":"10.1371\/journal.pone.0158369"},{"key":"80","doi-asserted-by":"crossref","unstructured":"J Le Blanc  and M Lordkipanidze  \"Front Cardiovasc Med.\"  6, \"Platelet function in aging.\" 109 (2019)","DOI":"10.3389\/fcvm.2019.00109"},{"key":"81","doi-asserted-by":"crossref","unstructured":"P Msaouel, AP Lam, K Gundabolu, et al.  \"Haematologica.\"  99, \"Abnormal platelet count is an independent predictor of mortality in the elderly and is influenced by ethnicity.\" 930 (2014)","DOI":"10.3324\/haematol.2013.101949"},{"key":"82","doi-asserted-by":"crossref","unstructured":"MT Tsai, YT Chen, CH Lin, et al.  \"Blood.\"  126, \"U-shaped mortality curve associated with platelet count among older people: a community-based cohort study.\" 1633 (2015)","DOI":"10.1182\/blood-2015-06-654764"},{"key":"83","doi-asserted-by":"crossref","unstructured":"JG van der Bom, SR Heckbert, T Lumley, et al.  \"J Thromb Haemost.\"  7, \"Platelet count and the risk for thrombosis and death in the elderly.\" 399 (2009)","DOI":"10.1111\/j.1538-7836.2008.03267.x"},{"key":"85","doi-asserted-by":"crossref","unstructured":"L Trtica Majnaric, S Guljas, Z Bosnic, et al.  \"Biomolecules.\"  11, \"Neutrophil-to-Lymphocyte ratio as a cardiovascular risk marker may be less efficient in women than in men.\" (2021)","DOI":"10.3390\/biom11040528"},{"key":"86","doi-asserted-by":"crossref","unstructured":"C Wenisch, S Patruta, F Daxbock, et al.  \"J Leukoc Biol.\"  67, \"Effect of age on human neutrophil function.\" 40 (2000)","DOI":"10.1002\/jlb.67.1.40"},{"key":"87","doi-asserted-by":"crossref","unstructured":"E Sapey, H Greenwood, G Walton, et al.  \"Blood.\"  123, \"Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence.\" 239 (2014)","DOI":"10.1182\/blood-2013-08-519520"},{"key":"88","doi-asserted-by":"crossref","unstructured":"MR Gubbels Bupp, T Potluri, AL Fink, et al.  \"Front Immunol.\"  9, \"The Confluence of sex hormones and aging on immunity.\" 1269 (2018)","DOI":"10.3389\/fimmu.2018.01269"},{"key":"89","doi-asserted-by":"crossref","unstructured":"SS Santos, MK Brunialti, O Rigato, et al.  \"Shock.\"  38, \"Generation of nitric oxide and reactive oxygen species by neutrophils and monocytes from septic patients and association with outcomes.\" 18 (2012)","DOI":"10.1097\/SHK.0b013e318257114e"},{"key":"90","doi-asserted-by":"crossref","unstructured":"I Kaufmann, A Hoelzl, F Schliephake, et al.  \"Shock.\"  26, \"Polymorphonuclear leukocyte dysfunction syndrome in patients with increasing sepsis severity.\" 254 (2006)","DOI":"10.1097\/01.shk.0000223131.64512.7a"},{"key":"91","doi-asserted-by":"crossref","unstructured":"J Nogueira-Neto, AS Cardoso, HP Monteiro, et al.  \"Cell Biol Int.\"  40, \"Basal neutrophil function in human aging: Implications in endothelial cell adhesion.\" 796 (2016)","DOI":"10.1002\/cbin.10618"},{"key":"92","doi-asserted-by":"crossref","unstructured":"HE Broxmeyer, S Cooper, ML Capitano,  \"Stem Cells.\"  38, \"Enhanced collection of phenotypic and engrafting human cord blood hematopoietic stem cells at 4 degrees C.\" 1326 (2020)","DOI":"10.1002\/stem.3243"},{"key":"93","doi-asserted-by":"crossref","unstructured":"ML Capitano, SF Mohamad, S Cooper, et al.  \"J Clin Invest.\"  2021, \"Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function.\" 131","DOI":"10.1172\/JCI140177"},{"key":"94","doi-asserted-by":"crossref","unstructured":"CR Mantel, HA O'Leary, BR Chitteti, et al.  \"Cell.\"  161, \"Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock.\" 1553 (2015)","DOI":"10.1016\/j.cell.2015.04.054"},{"key":"95","doi-asserted-by":"crossref","unstructured":"Y Morita, H Ema, H Nakauchi,  \"J Exp Med.\"  207, \"Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment.\" 1173 (2010)","DOI":"10.1084\/jem.20091318"},{"key":"96","doi-asserted-by":"crossref","unstructured":"JM Nygren  and D Bryder  \"PLoS One.\"  3, \"A novel assay to trace proliferation history in vivo reveals that enhanced divisional kinetics accompany loss of hematopoietic stem cell self-renewal.\" e3710 (2008)","DOI":"10.1371\/journal.pone.0003710"},{"key":"97","doi-asserted-by":"crossref","unstructured":"DM Christensen, CJ Iddins, SL Sugarman,  \"Emerg Med Clin North Am.\"  32, \"Ionizing radiation injuries and illnesses.\" 245 (2014)","DOI":"10.1016\/j.emc.2013.10.002"},{"key":"99","doi-asserted-by":"crossref","unstructured":"S Chang, NE Goldstein, KV Dharmarajan,  \"Biomed Res Int.\"  2017, \"Managing an older adult with cancer: Considerations for radiation oncologists.\" 1695101 (2017)","DOI":"10.1155\/2017\/1695101"},{"key":"100","doi-asserted-by":"crossref","unstructured":"Z Chen, EM Amro, F Becker, et al.  \"J Exp Med.\"  216, \"Cohesin-mediated NF-kappaB signaling limits hematopoietic stem cell self-renewal in aging and inflammation.\" 152 (2019)","DOI":"10.1084\/jem.20181505"},{"key":"101","doi-asserted-by":"crossref","unstructured":"Y Hirabayashi, I Tsuboi, K Kuramoto, et al.  \"Exp Biol Med (Maywood).\"  241, \"Cell cycle of primitive hematopoietic progenitors decelerated in senescent mice is reactively accelerated after 2-Gy whole-body irradiation.\" 485 (2016)","DOI":"10.1177\/1535370215625472"},{"key":"102","doi-asserted-by":"crossref","unstructured":"AB Martinez-Martinez, E Torres-Perez, N Devanney, et al.  \"Neurobiol Dis.\"  138, \"Beyond the CNS: The many peripheral roles of APOE.\" 104809 (2020)","DOI":"10.1016\/j.nbd.2020.104809"},{"key":"103","doi-asserted-by":"crossref","unstructured":"G Tie, KE Messina, J Yan, et al.  \"J Am Heart Assoc.\"  3, \"Hypercholesterolemia induces oxidant stress that accelerates the ageing of hematopoietic stem cells.\" e000241 (2014)","DOI":"10.1161\/JAHA.113.000241"},{"key":"104","doi-asserted-by":"crossref","unstructured":"JN Smith, VS Kanwar, KC MacNamara,  \"Front Immunol.\"  7, \"Hematopoietic stem cell regulation by type I and II interferons in the pathogenesis of acquired aplastic anemia.\" 330 (2016)","DOI":"10.3389\/fimmu.2016.00330"},{"key":"105","doi-asserted-by":"crossref","unstructured":"XX Hong  and GG Carmichael  \"J Biol Chem.\"  288, \"Innate immunity in pluripotent human cells: attenuated response to interferon-beta.\" 16196 (2013)","DOI":"10.1074\/jbc.M112.435461"},{"key":"106","doi-asserted-by":"crossref","unstructured":"X Wu, VL Dao Thi, Y Huang, et al.  \"Cell.\"  172, \"Intrinsic immunity shapes viral resistance of stem cells.\" 423 (2018)","DOI":"10.1016\/j.cell.2017.11.018"},{"key":"107","doi-asserted-by":"crossref","unstructured":"NY Villa, S Bais, WM Chan, et al.  \"Cytotherapy.\"  18, \"Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells.\" 465 (2016)","DOI":"10.1016\/j.jcyt.2015.12.007"},{"key":"108","doi-asserted-by":"crossref","unstructured":"H Shen, T Cheng, FI Preffer, et al.  \"J Virol.\"  73, \"Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite coreceptor expression.\" 728 (1999)","DOI":"10.1128\/JVI.73.1.728-737.1999"},{"key":"109","doi-asserted-by":"crossref","unstructured":"Q Yu, YV Katlinskaya, CJ Carbone, et al.  \"Cell Rep.\"  11, \"DNA-damage-induced type I interferon promotes senescence and inhibits stem cell function.\" 785 (2015)","DOI":"10.1016\/j.celrep.2015.03.069"},{"key":"4","doi-asserted-by":"crossref","unstructured":"PA Plett, CH Sampson, HL Chua, et al.  \"Health Phys.\"  103, \"Establishing a murine model of the hematopoietic syndrome of the acute radiation syndrome.\" 343 (2012)","DOI":"10.1097\/HP.0b013e3182667309"},{"key":"61","doi-asserted-by":"crossref","unstructured":"J Garrett, CM Orschell, MS Mendonca, et al.  \"Radiat Res.\"  181, \"Subcutaneous wounding postirradiation reduces radiation lethality in mice.\" 578 (2014)","DOI":"10.1667\/RR13267.1"},{"key":"32","doi-asserted-by":"crossref","unstructured":"Y Liao, GK Smyth, W Shi,  \"Bioinformatics.\"  30, \"Featurecounts: An efficient general purpose program for assigning sequence reads to genomic features.\" 923 (2014)","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"33","doi-asserted-by":"crossref","unstructured":"P Ewels, M Magnusson, S Lundin, et al.  \"Bioinformatics.\"  32, \"MultiQC: Summarize analysis results for multiple tools and samples in a single report.\" 3047 (2016)","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"34","doi-asserted-by":"crossref","unstructured":"MD Robinson, DJ McCarthy, GK Smyth,  \"Bioinformatics.\"  26, \"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.\" 139 (2010)","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"36","doi-asserted-by":"crossref","unstructured":"W Huang da, BT Sherman, RA Lempicki,  \"Nat Protoc.\"  4, \"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.\" 44 (2009)","DOI":"10.1038\/nprot.2008.211"},{"key":"11","doi-asserted-by":"crossref","unstructured":"AN Shakhov, VK Singh, F Bone, et al.  \"PLoS One.\"  7, \"Prevention and mitigation of acute radiation syndrome in mice by synthetic lipopeptide agonists of Toll-like receptor 2 (TLR2).\" e33044 (2012)","DOI":"10.1371\/journal.pone.0033044"},{"key":"35","doi-asserted-by":"crossref","unstructured":"DJ McCarthy, Y Chen, GK Smyth,  \"Nucleic Acids Res.\"  40, \"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation.\" 4288 (2012)","DOI":"10.1093\/nar\/gks042"},{"key":"37","doi-asserted-by":"crossref","unstructured":"W Huang da, BT Sherman, RA Lempicki,  \"Nucleic Acids Res.\"  37, \"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists.\" 1 (2009)","DOI":"10.1093\/nar\/gkn923"},{"key":"98","doi-asserted-by":"crossref","unstructured":"J Bergonie  and L Tribondeau  \"Radiat Res.\"  11, \"Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment.\" 587 (1959)","DOI":"10.2307\/3570812"},{"key":"9","doi-asserted-by":"crossref","unstructured":"J Hoggatt, P Singh, KN Stilger, et al.  \"Blood Cells Mol Dis.\"  50, \"Recovery from hematopoietic injury by modulating prostaglandin E(2) signaling post-irradiation.\" 147 (2013)","DOI":"10.1016\/j.bcmd.2012.11.006"},{"key":"59","doi-asserted-by":"crossref","unstructured":"JR Dynlacht, J Garrett, R Joel, et al.  \"Radiat Res.\"  187, \"Further Characterization of the Mitigation of Radiation Lethality by Protective Wounding.\" 732 (2017)","DOI":"10.1667\/RR14725.1"},{"key":"40","doi-asserted-by":"crossref","unstructured":"J Spalding, O Johnson, R Archuleta,  \"Nature.\"  208, \"Acute radio-sensitivity as a function of age in mice.\" 905 (1965)","DOI":"10.1038\/208905a0"},{"key":"28","doi-asserted-by":"crossref","unstructured":"D. Boggs,  \"Am J Hematol.\"  16, \"The total marrow mass of the mouse: A simplified method of measurement.\" 277 (1984)","DOI":"10.1002\/ajh.2830160309"},{"key":"43","doi-asserted-by":"crossref","unstructured":"J Garrett, CH Sampson, PA Plett, et al.  \"Radiat Res.\"  191, \"Characterization and etiology of swollen muzzles in irradiated mice.\" 31 (2019)","DOI":"10.1667\/RR14724.1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"AM Patterson, PA Plett, HL Chua, et al.  \"Health Phys.\"  119, \"Development of a model of the acute and delayed effects of high dose radiation exposure in Jackson diversity outbred mice; comparison to inbred C57BL\/6 mice.\" 633 (2020)","DOI":"10.1097\/HP.0000000000001344"},{"key":"12","unstructured":"\"Product development under the animal rule: Guidance for industry.\"  (2015)"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00071.1\/3086684\/10.1667_rade-22-00071.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-22-00071.1\/3086684\/10.1667_rade-22-00071.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T07:07:18Z","timestamp":1793430438000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-198\/issue-3\/RADE-22-00071.1\/Age-and-Sex-Divergence-in-Hematopoietic-Radiosensitivity-in-Aged-Mouse\/10.1667\/RADE-22-00071.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":109,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,9,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-22-00071.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}