{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:41:44Z","timestamp":1773808904680,"version":"3.50.1"},"reference-count":162,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007258","name":"State University of New York","doi-asserted-by":"publisher","award":["The EMPIRE innovative program"],"award-info":[{"award-number":["The EMPIRE innovative program"]}],"id":[{"id":"10.13039\/100007258","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR\u2019s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.<\/jats:p>","DOI":"10.3390\/cancers13133180","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"3180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4829-1444","authenticated-orcid":false,"given":"Evan","family":"Maestri","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Department of Biology, SUNY University at Buffalo, Buffalo, NY 14260, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-6090","authenticated-orcid":false,"given":"Kalina","family":"Duszka","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir A.","family":"Kuznetsov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Urology, SUNY Upstate Medical University, Syracuse, NY 13210, USA"},{"name":"Bioinformatics Institute, Biomedical Sciences Institutes A*STAR, Singapore 13867, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1126\/science.1173635","article-title":"Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys","volume":"325","author":"Colman","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/carcin\/bgp280","article-title":"Calories and carcinogenesis: Lessons learned from 30 years of calorie restriction research","volume":"31","author":"Hursting","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3177\/jnsv.47.13","article-title":"Caloric Restriction and Cancer","volume":"47","author":"Kritchevsky","year":"2001","journal-title":"J. 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