{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:57:41Z","timestamp":1791244661278,"version":"4.1.0"},"reference-count":42,"publisher":"Radiation Research Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:p>Delayed effects of acute radiation exposure (DEARE) and radiation late effects are a suite of conditions that become apparent months to years after initial exposure to radiation in both humans and non-human primates. Many of these disorders, including cardiac complications, insulin resistance, bone loss, hypertension, and others, are also more common among aging cohorts independent of radiation exposure. This study characterized disease incidence, age of onset, and multimorbidity for 20 common, chronic diseases in 226 irradiated and 51 control rhesus macaques (Macaca mulatta) from the Wake Forest Non-Human Primate Radiation Late Effects Cohort (RLEC) to identify the excess risk of chronic disease caused by radiation-induced tissue damage. Irradiated animals were exposed to 4.0\u20138.5 Gy of ionizing radiation (mean 6.17 \u00b1 1.29 Gy) one year on average prior to joining the cohort. In addition to the acute impact of early-life irradiation, these animals have been aging postirradiation for up to 15 years (mean 5.2 \u00b1 3.0 years). Lifespan is an average of 5.1 years shorter in irradiated animals and radiation is associated with significantly increased rates of periodontitis, cataracts, testicular atrophy, tumors, diabetes, and brain lesions. While most of these chronic diseases occur in non-irradiated macaques, irradiated animals have significantly earlier age of onset for periodontitis, cataracts, bone loss, being overweight, and arthritis. This accelerated onset leads to 2.9 \u00b1 1.9 comorbid conditions among irradiated animals compared to 1.9 \u00b1 1.2 diagnoses among controls by young adulthood (age 8) and 5.2 \u00b1 2.4 compared to 3.4 \u00b1 1.8 conditions by middle age (15 years). Subsets of these comorbid conditions cluster among animals with fibrosis-related disorders (diabetes, lung injury, liver disease, kidney disease, heart disease, and tumors) commonly diagnosed together independent of prevalence. A second cluster of comorbidities centers around bone loss and is associated with being underweight and female reproductive problems. While there are significant differences in disease burden between irradiated and control animals, there was no dose effect of radiation on lifespan, age to first diagnosis, or comorbidities and substantial heterogeneity across each of these measures. This underlying heterogeneity in response to radiation suggests the existence of a yet unidentified determinant of resilience.<\/jats:p>","DOI":"10.1667\/rade-24-00014.1","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T01:16:27Z","timestamp":1741569387000},"page":"283-293","source":"Crossref","is-referenced-by-count":2,"title":["Widespread Multimorbidity in a Cohort of Aging, Radiation-exposed Rhesus Macaques"],"prefix":"10.1667","volume":"204","author":[{"given":"Ellen E.","family":"Quillen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Molecular Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George W.","family":"Schaaf","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie N.","family":"Justice","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Gerontology and Geriatrics, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory O.","family":"Dugan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Mark","family":"Cline","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Comparative Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"37","doi-asserted-by":"crossref","unstructured":"GR Yannam, B Han, K Setoyama, et al.  \"Int J Radiat Oncol Biol Phys.\"  88, \"A nonhuman primate model of human radiation-induced venocclusive liver disease and hepatocyte injury.\" 404 (2014)","DOI":"10.1016\/j.ijrobp.2013.10.037"},{"key":"19","doi-asserted-by":"crossref","unstructured":"GW Schaaf, JN Justice, EE Quillen, et al.  \"Geroscience.\"  45, \"Resilience, aging, and response to radiation exposure (RARRE) in nonhuman primates: a resource review.\" 3371 (2023)","DOI":"10.1007\/s11357-023-00812-7"},{"key":"32","doi-asserted-by":"crossref","unstructured":"GA Parker, EP Cohen, N Li, et al.  \"Health Phys.\"  116, \"Radiation nephropathy in a nonhuman primate model of partial-body irradiation with minimal bone marrow sparing-part 2: histopathology, mediators, and mechanisms.\" 409 (2019)","DOI":"10.1097\/HP.0000000000000935"},{"key":"2","doi-asserted-by":"publisher","unstructured":"N Bacarella, A Ruggiero, AT Davis, et al.  \"Int J Radiat Oncol Biol Phys.\"  106, \"Whole body irradiation induces diabetes and adipose insulin resistance in nonhuman primates.\" 878 (2020)","DOI":"10.1016\/j.ijrobp.2019.11.034"},{"key":"18","doi-asserted-by":"crossref","unstructured":"WS Sills, JA Tooze, JD Olson, et al.  \"Int J Radiat Oncol Biol Phys.\"  113, \"Total-body irradiation is associated with increased incidence of mesenchymal neoplasia in a radiation late effects cohort of rhesus macaques (Macaca mulatta).\" 661 (2022)","DOI":"10.1016\/j.ijrobp.2022.02.019"},{"key":"4","doi-asserted-by":"crossref","unstructured":"B Johnson, R Barcus, J Olson, et al.  \"Int J Rad Onc Biol Phys.\"  119, \"Total-body irradiation alters white matter volume and microstructural integrity in rhesus macaques.\" 208 (2024)","DOI":"10.1016\/j.ijrobp.2023.11.014"},{"key":"13","doi-asserted-by":"crossref","unstructured":"JL Unthank, SJ Miller, AK Quickery, et al.  \"Health Phys.\"  109, \"Delayed effects of acute radiation exposure in a murine model of the H-ARS.\" 511 (2015)","DOI":"10.1097\/HP.0000000000000357"},{"key":"14","doi-asserted-by":"crossref","unstructured":"G Shetty, JM Mitchell, TNA Lam, et al.  \"Andrology.\"  9, \"Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty.\" 1603 (2021)","DOI":"10.1111\/andr.13033"},{"key":"15","doi-asserted-by":"publisher","unstructured":"GW Schaaf, JD Olson, GO Dugan, et al.  \"Radiat Res.\"  200, \"Dose-dependent testicular injury and recovery after total-body irradiation in rhesus monkeys.\" 321 (2023)","DOI":"10.1667\/RADE-23-00008.1.S1"},{"key":"16","doi-asserted-by":"crossref","unstructured":"P Sonneveld, E Peperkamp, DW van Bekkum,  \"Radiology.\"  133, 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(2019)"},{"key":"33","doi-asserted-by":"crossref","unstructured":"M van Kleef, C Zurcher, Y Ous,  \"Int J Radiat Biol.\"  76, \"Long-term effects of total-body irradiation on the kidney of rhesus monkeys.\" 641 (2000)","DOI":"10.1080\/095530000138303"},{"key":"35","doi-asserted-by":"crossref","unstructured":"P Thakur, JD Olson, GO Dugan, et al.  \"Radiat Res.\"  199, \"Quantitative assessment and comparative analysis of longitudinal lung CT scans of chest-irradiated nonhuman primates.\" 39 (2023)","DOI":"10.1667\/RADE-21-00225.1"},{"key":"38","doi-asserted-by":"crossref","unstructured":"G Chodick, N Bekiroglu, M Hauptmann, et al.  \"Am J Epidemiol.\"  168, \"Risk of cataract after exposure to low doses of ionizing radiation: A 20-year prospective sohort study among US radiologic technologists.\" 620 (2008)","DOI":"10.1093\/aje\/kwn171"},{"key":"40","doi-asserted-by":"crossref","unstructured":"KT Michalson, AN Macintyre, GD Sempowski, et al.  \"Radiat Res.\"  192, \"Monocyte polarization is altered by total-body irradiation in male rhesus macaques: Implications for delayed rffects of acute radiation exposure.\" 121 (2019)","DOI":"10.1667\/RR15310.1"},{"key":"41","doi-asserted-by":"crossref","unstructured":"RE Vatner, A Niemierko, M Misra, et al.  \"J Clin Oncol.\"  36, \"Endocrine deficiency as a function of radiation dose to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors.\" 2854 (2018)","DOI":"10.1200\/JCO.2018.78.1492"},{"key":"42","doi-asserted-by":"crossref","unstructured":"S Achilles, JD Olson, GO Dugan, et al.  \"Radiat Res.\"  200, \"Assessment of blood pressure in irradiated rhesus macaques (Macaca mulatta).\" 13 (2023)","DOI":"10.1667\/RADE-22-00117.1"},{"key":"20","unstructured":"\"Guide for the care and use of laboratory animals.\"  (2011)"},{"key":"7","doi-asserted-by":"crossref","unstructured":"KM Fanning, B Pfisterer, AT Davis, et al.  \"Am J Physiol Regul Integr Comp Physiol.\"  313, \"Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling.\" R290 (2017)","DOI":"10.1152\/ajpregu.00108.2017"},{"key":"23","doi-asserted-by":"crossref","unstructured":"JZ Yu, M Lindeblad, A Lyubimov, et al.  \"Radiat Res.\"  184, \"Subject-based versus population-based care after radiation exposure.\" 46 (2015)","DOI":"10.1667\/RR13918.1"},{"key":"17","doi-asserted-by":"publisher","unstructured":"DL Preston, E Ron, S Tokuoka, et al.  \"Radiat Res.\"  168, \"Solid cancer incidence in atomic bomb survivors: 1958\u20131998.\" 1 (2007)","DOI":"10.1667\/RR0763.1"},{"key":"1","doi-asserted-by":"publisher","unstructured":"RJ DeBo, CJ Lees, GO Dugan, et al.  \"Radiat Res.\"  186, \"Late effects of total-body gamma irradiation on cardiac structure and function in male rhesus macaques.\" 55 (2016)","DOI":"10.1667\/RR14357.1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"DB Hanbury, AM Peiffer, G Dugan, et al.  \"Radiat Res.\"  186, \"Long-term cognitive functioning in single-dose total-body gamma-irradiated rhesus monkeys (Macaca mulatta).\" 447 (2016)","DOI":"10.1667\/RR14430.1"},{"key":"36","doi-asserted-by":"crossref","unstructured":"SA Ghandhi, HC Turner, I Shuryak, et al.  \"PloS One.\"  13, \"Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.\" e0191402 (2018)","DOI":"10.1371\/journal.pone.0191402"},{"key":"3","doi-asserted-by":"publisher","unstructured":"K Kavanagh, MD Dendinger, AT Davis, et al.  \"Radiat Res.\"  183, \"Type 2 diabetes is a delayed late effect of whole-body irradiation in nonhuman primates.\" 398 (2015)","DOI":"10.1667\/Rr13916.1"},{"key":"8","doi-asserted-by":"crossref","unstructured":"M Farris, ER McTyre, C Okoukoni, et al.  \"Radiat Res.\"  190, \"cortical thinning and structural bone changes in non-human primates after single-fraction whole-chest irradiation.\" 63 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Therneau,  \"A package for survival analysis in R.\"  (2023)"},{"key":"29","doi-asserted-by":"publisher","unstructured":"TM Therneau  and PM Grambsch  \"Modeling survival data: extending the Cox model.\"  (2000)","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"39","doi-asserted-by":"crossref","unstructured":"RB Richardson, EA Ainsbury, CR Prescott, et al.  \"Int J Radiat Biol.\"  96, \"Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation.\" 1339 (2020)","DOI":"10.1080\/09553002.2020.1812759"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-24-00014.1\/3498308\/10.1667_rade-24-00014.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-24-00014.1\/3498308\/10.1667_rade-24-00014.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:29:47Z","timestamp":1791242987000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-204\/issue-4\/RADE-24-00014.1\/Widespread-Multimorbidity-in-a-Cohort-of-Aging-Radiation-exposed-Rhesus\/10.1667\/RADE-24-00014.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,10,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-24-00014.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]}}}