{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:59:45Z","timestamp":1791680385796,"version":"4.3.4"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL148352"],"award-info":[{"award-number":["HL148352"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG050777"],"award-info":[{"award-number":["AG050777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H2S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H2S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H2S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H2S generation, with translational implications for radiation treatment and aging.<\/jats:p>","DOI":"10.3390\/nu14071529","type":"journal-article","created":{"date-parts":[[2022,4,7]],"date-time":"2022-04-07T21:08:22Z","timestamp":1649365702000},"page":"1529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-7939","authenticated-orcid":false,"given":"Christopher","family":"Hine","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Humberto","family":"Trevi\u00f1o-Villarreal","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Service of Endocrinology, Department of Internal Medicine, University Hospital and School of Medicine, Universidad Autonoma de Nuevo Leon, Monterrey N.L. 64460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Mejia","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alban","family":"Longchamp","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lear E.","family":"Brace","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eylul","family":"Harputlugil","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Health Sciences and Technology, ETH Zurich, 8005 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-3792","authenticated-orcid":false,"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-5141","authenticated-orcid":false,"given":"Yihong","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5255","authenticated-orcid":false,"given":"Babal K.","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology & Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism (Formally Genetics and Complex Diseases), Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Health Sciences and Technology, ETH Zurich, 8005 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/0360-3016(94)00430-S","article-title":"Hematopoietic stem cell compartment: Acute and late effects of radiation therapy and chemotherapy","volume":"31","author":"Mauch","year":"1995","journal-title":"Int. J. Radiat. Oncol. Biol. 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