{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T14:43:26Z","timestamp":1764859406096,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>A stem-cell theory of cancer predicates that not only does the cell affect the niche, the niche also affects the cell. It implicates that even though genetic makeup may be supreme, cellular context is key. When we attempt to solve the mystery of a long cancer-free life, perhaps we need to search no further than the genetics and epigenetics of the naked mole-rat. When we try to unlock the secrets in the longevity and quality of life, perhaps we need to look no further than the lifestyle and habits of the super centenarians. We speculate that people with Down\u2019s syndrome and progeria age faster but have fewer cancers, because they are depleted of stem cells, and, as a consequence, have fewer opportunities for stem cell defects that could predispose them to the development of cancer. We contemplate whether these incredible experiments of nature may provide irrefutable evidence that cancer is a stem-cell disease\u2014fewer aberrant stem cells, fewer cancers; no defective stem cells, no cancer. In this perspective, we investigate a stem-cell origin of aging and cancer. We elaborate an intriguing inverse relationship between longevity and malignancy in the naked mole-rat, in Down\u2019s syndrome, and in progeria. We postulate that stem-cell pools and stemness factors may affect aging and dictate cancer. We propose that a healthy microbiome may protect and preserve stem cell reserves and provide meaningful antiaging effects and anticancer benefits.<\/jats:p>","DOI":"10.3390\/cancers14051338","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:35:50Z","timestamp":1646598950000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stem-Cell Theory of Cancer: Implications for Antiaging and Anticancer Strategies"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-2111","authenticated-orcid":false,"given":"Shi-Ming","family":"Tu","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis L.","family":"Pisters","sequence":"additional","affiliation":[{"name":"Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20150198","DOI":"10.1098\/rstb.2015.0198","article-title":"Quantitative implications of the approximate irrelevance of mammalian body size and lifespan to lifelong cancer risk","volume":"370","author":"Peto","year":"2015","journal-title":"Philos. 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