{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:50:37Z","timestamp":1791546637628,"version":"4.3.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Starting in the 1950s or earlier, irradiation was found to shorten lifespans in mice, which raised the possibility that radiation science might contribute to an understanding of the nature of aging. However, in 1975, Walburg published a review paper to express his hypothesis that radiation exposure increases the risk of tumor deaths but not for non-tumor deaths. Subsequently, it became a mainstream belief that irradiation induces oncogenic mutations and thereby increases the risk of cancer and thus life shortening. However, we now think that the Walburg\u2019s hypothesis is not tenable as it did not include contradictory studies that were available before 1975, and additional contradictory papers were published after 1975; namely, all irradiated individuals are affected. If we accept the notion that irradiation shortens the lifespan of all individuals regardless of the cause of death, it suggests that irradiation may accelerate general aging. Based on these considerations and other available evidence in the field, the mutation induction theory appears untenable as the sole mechanism in radiation carcinogenesis. Under such conditions, the old hypothesis that radiation induces accelerated aging should be revived. Current knowledge in the field of natural aging supports the hypothesis that radiation causes DNA breaks, most of which are correctly repaired, but not at the chromatin level (chromatin fatigue) which leads to accelerated aging. The critical difference from the traditional mutagenesis model is that no stem cell mutagenesis is necessary to consider.<\/jats:p>","DOI":"10.1093\/jrr\/rrag063","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:49:49Z","timestamp":1789127389000},"page":"694-702","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting the Walburg hypothesis that radiation affects only tumor deaths but not non-tumor deaths in mice"],"prefix":"10.1093","volume":"67","author":[{"given":"Nori","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, Radiation Effects Research Foundation , Hiroshima ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Radiobiology, AMBIC, Institute for Environmental Sciences , Rokkasho, Aomori ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Ignacia Braga","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Radiobiology, AMBIC, Institute for Environmental Sciences , Rokkasho, Aomori ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-5085","authenticated-orcid":false,"given":"Yoshiya","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Radiobiology, AMBIC, Institute for Environmental Sciences , Rokkasho, Aomori ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026100906563701800_ref1","first-page":"174","article-title":"Accelerated ageing: a long-term effect of exposure to ionizing radiations","volume":"1","author":"Alexander","year":"1957","journal-title":"Gerontologia"},{"key":"2026100906563701800_ref2","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1093\/geronj\/12.3.306","article-title":"Ionizing radiation and the aging process; a review","volume":"12","author":"Upton","year":"1957","journal-title":"J Gerontol"},{"key":"2026100906563701800_ref3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/B978-0-12-035405-4.50010-4","article-title":"Radiation-induced life-shortening and premature aging","volume":"5","author":"Walburg","year":"1975","journal-title":"Adv Radiat Biol"},{"key":"2026100906563701800_ref4","first-page":"p570","volume-title":"Ionizing Radiation: Sources and Biological Effects 1977 Report to the General Assembly, with Annexes","author":"United Nations Scientific Committee on the effects of ionizing radiation"},{"key":"2026100906563701800_ref5","first-page":"p 661","volume-title":"Ionizing Radiation: Sources and Biological Effects 1982 Report to the General Assembly, with Annexes","author":"United Nations Scientific Committee on the effects of ionizing radiation","year":"1982"},{"key":"2026100906563701800_ref6","doi-asserted-by":"publisher","first-page":"545","DOI":"10.2307\/3570808","article-title":"Late effects of fast neutrons versus x-rays in mice: nephrosclerosis, tumors, longevity","volume":"11","author":"Nowell","year":"1959","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref7","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1667\/RR3042","article-title":"No lengthening of life span in mice continuously exposed to gamma rays at very low dose rates","volume":"160","author":"Tanaka","year":"2003","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1667\/RR0728.1","article-title":"Cause of death and neoplasia in mice continuously exposed to very low dose rates of gamma rays","volume":"167","author":"Tanaka","year":"2007","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref9","doi-asserted-by":"publisher","first-page":"20190843","DOI":"10.1259\/bjr.20190843","article-title":"A hypothesis: radiation carcinogenesis may result from tissue injuries and subsequent recovery processes which can act as tumor promoters and lead to an earlier onset of cancer","volume":"93","author":"Nakamura","year":"2020","journal-title":"Br J Radiol"},{"key":"2026100906563701800_ref10","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1080\/09553002.2023.2158246","article-title":"Radiation-induced increases in cancer mortality result from an earlier onset of the disease in mice and atomic bomb survivors","volume":"99","author":"Nakamura","year":"2023","journal-title":"Int J Radiat Biol"},{"key":"2026100906563701800_ref11","first-page":"1948","article-title":"252Cf relative biological effectiveness and inheritable effect of fission neutrons in mouse liver tumorigenesis","volume":"52","author":"Takahashi","year":"1992","journal-title":"Cancer Res"},{"key":"2026100906563701800_ref12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2307\/3575061","article-title":"Influence of gamma irradiation on the development of neoplastic disease in mice. III. Dose-rate effects","volume":"80","author":"Ullrich","year":"1979","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref13","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1080\/09553002.2024.2338516","article-title":"Reasons why the idea that radiation exposures induce cancer needs to be revisited","volume":"100","author":"Nakamura","year":"2024","journal-title":"Int J Radiat Biol"},{"key":"2026100906563701800_ref14","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2307\/3572262","article-title":"Late effects of fast neutrons and gamma rays in mice as influenced by the dose rate of irradiation: life shortening","volume":"32","author":"Upton","year":"1967","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref15","doi-asserted-by":"publisher","first-page":"81","DOI":"10.2307\/3579399","article-title":"The influence of sex on life shortening and tumor induction in CBA\/Cne mice exposed to X rays or fission neutrons","volume":"146","author":"Di Majo","year":"1996","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref16","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1667\/RR1875.1","article-title":"Cancer and non-cancer risks in normal and cancer-prone Trp53 heterozygous mice exposed to high-dose radiation","volume":"173","author":"Carlisle","year":"2010","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref17","first-page":"1","article-title":"Some delayed effects of atomic-bomb radiation in mice","volume":"20","author":"Upton","year":"1960","journal-title":"Cancer Res"},{"key":"2026100906563701800_ref18","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1098\/rspb.1961.0036","article-title":"Long-term effects of a single whole-body exposure of mice to ionizing radiation. II. Causes of death","volume":"154","author":"Lindop","year":"1961","journal-title":"Proc Roy Soc"},{"key":"2026100906563701800_ref19","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1080\/09553002.2017.1290849","article-title":"Cardiovascular disease among atomic bomb survivors","volume":"93","author":"Ozasa","year":"2017","journal-title":"Int J Radiat Biol"},{"key":"2026100906563701800_ref20","doi-asserted-by":"publisher","first-page":"435","DOI":"10.2307\/3571760","article-title":"Radiation resistance with age in normal and irradiated populations of mice","volume":"25","author":"Storer","year":"1965","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref21","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2307\/3577229","article-title":"Extrapolation of the relative risk of radiogenic neoplasms across mouse strains and to man","volume":"114","author":"Storer","year":"1988","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1269\/jrr.46.1","article-title":"Temporal variation of excess mortality rate from solid tumors in mice irradiated at various ages with gamma rays","volume":"46","author":"Sasaki","year":"2005","journal-title":"J Radiat Res"},{"key":"2026100906563701800_ref23","first-page":"717","article-title":"The dose-response relation in radiation-induced cancer","volume":"21","author":"Upton","year":"1961","journal-title":"Cancer Res"},{"key":"2026100906563701800_ref24","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1749-6632.1964.tb53574.x","article-title":"Myeloid leukemia in the mouse","volume":"114","author":"Upton","year":"1964","journal-title":"Ann N Y Acad Sci"},{"key":"2026100906563701800_ref25","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1002\/ijc.2910030118","article-title":"Influence of microbial environment on development of myeloid leukemia in X-irradiated RFM mice","volume":"3","author":"Walburg","year":"1968","journal-title":"Int J Cancer"},{"key":"2026100906563701800_ref26","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1002\/ijc.28751","article-title":"Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice","volume":"135","author":"Shang","year":"2014","journal-title":"Int J Cancer"},{"key":"2026100906563701800_ref27","doi-asserted-by":"publisher","first-page":"467","DOI":"10.2307\/3572837","article-title":"Late effects of fast neutrons and gamma-rays in mice as influenced by the dose rate of irradiation: induction of neoplasia","volume":"41","author":"Upton","year":"1970","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref28","first-page":"361","article-title":"Statistical analysis of survival experiments","volume":"49","author":"Hoel","year":"1972","journal-title":"J Natl Cancer Inst"},{"key":"2026100906563701800_ref29","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/bmj.2.5090.181","article-title":"Expectation of life and mortality from cancer among British radiologists","volume":"2","author":"Court Brown","year":"1958","journal-title":"Br Med J"},{"key":"2026100906563701800_ref30","doi-asserted-by":"publisher","first-page":"649","DOI":"10.2307\/3573560","article-title":"Studies of the mortality of A-bomb survivors. 5. Radiation dose and mortality, 1950-1970","volume":"50","author":"Jablon","year":"1972","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref31","doi-asserted-by":"publisher","first-page":"374","DOI":"10.2307\/3580222","article-title":"Studies of the mortality of atomic bomb survivors. Report 12, part II. Noncancer mortality: 1950-1990","volume":"152","author":"Shimizu","year":"1999","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09553002.2025.2575502","article-title":"Organ-specific cancer risks following exposure to radiation can be explained by a shift of spontaneously arising cancers toward younger ages","volume":"102","author":"Nakamura","year":"2026","journal-title":"Int J Radiat Biol"},{"key":"2026100906563701800_ref33","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1667\/RR3049","article-title":"Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950-1997","volume":"160","author":"Preston","year":"2003","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref34","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1667\/RR3183","article-title":"Noncancer disease incidence in atomic bomb survivors, 1958-1998","volume":"161","author":"Yamada","year":"2004","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/0146645316629318","article-title":"Radiation-related risks of non-cancer outcomes in the atomic bomb survivors","volume":"45","author":"Ozasa","year":"2016","journal-title":"Ann ICRP"},{"key":"2026100906563701800_ref36","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":"2026100906563701800_ref37","doi-asserted-by":"publisher","first-page":"i145","DOI":"10.1093\/jrr\/rrt211","article-title":"Systems biology perspectives on the carcinogenic potential of radiation","volume":"55","author":"Barcellos-Hoff","year":"2014","journal-title":"J Radiat Res"},{"key":"2026100906563701800_ref38","doi-asserted-by":"publisher","first-page":"106","DOI":"10.2307\/3571700","article-title":"Effect of age at irradiation on life span in the male rat","volume":"22","author":"Jones","year":"1964","journal-title":"Radiat Res"},{"key":"2026100906563701800_ref39","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/09553002.2024.2442690","article-title":"An examination of the dose rate effect in mice assuming that the carcinogenic effect of radiation is life shortening resulting from a tissue reaction","volume":"101","author":"Nakamura","year":"2025","journal-title":"Int J Radiat Biol"},{"key":"2026100906563701800_ref40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-4-431-55763-0_1","volume-title":"Aging Mechanisms: Longevity, Metabolism, and Brain Aging","author":"Goto","year":"2015"},{"key":"2026100906563701800_ref41","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.molcel.2016.05.013","article-title":"The aging epigenome","volume":"62","author":"Booth","year":"2016","journal-title":"Mol Cell"},{"key":"2026100906563701800_ref42","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.cell.2022.12.027","article-title":"Loss of epigenetic information as a cause of mammalian aging","volume":"186","author":"Yang","year":"2023","journal-title":"Cell"}],"container-title":["Journal of Radiation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jrr\/article-pdf\/67\/5\/694\/71122500\/rrag063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jrr\/article-pdf\/67\/5\/694\/71122500\/rrag063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:56:44Z","timestamp":1791543404000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jrr\/article\/67\/5\/694\/8802026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9,16]]},"published-print":{"date-parts":[[2026,10,9]]}},"URL":"https:\/\/doi.org\/10.1093\/jrr\/rrag063","relation":{},"ISSN":["0449-3060","1349-9157"],"issn-type":[{"value":"0449-3060","type":"print"},{"value":"1349-9157","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,9]]}}}