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Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.
Tomasetti, Cristian; Poling, Justin; Roberts, Nicholas J; London, Nyall R; Pittman, Meredith E; Haffner, Michael C; Rizzo, Anthony; Baras, Alex; Karim, Baktiar; Kim, Antonio; Heaphy, Christopher M; Meeker, Alan K; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Vogelstein, Bert.
  • Tomasetti C; Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; bertvog@gmail.com ctomasetti@jhu.edu.
  • Poling J; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21205.
  • Roberts NJ; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
  • London NR; Pathology, Williamson Medical Center, Brentwood, TN 37207.
  • Pittman ME; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21205.
  • Haffner MC; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD 21231.
  • Rizzo A; Department of Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Baras A; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065.
  • Karim B; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21205.
  • Kim A; Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231.
  • Heaphy CM; Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231.
  • Meeker AK; Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231.
  • Hruban RH; Pathology & Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702.
  • Iacobuzio-Donahue CA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21205.
  • Vogelstein B; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21205.
Proc Natl Acad Sci U S A ; 116(41): 20482-20488, 2019 10 08.
Article en En | MEDLINE | ID: mdl-31548407
ABSTRACT
A new evaluation of previously published data suggested to us that the accumulation of mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized that normal stem cell division rates might decrease as we age. To test this hypothesis, we evaluated cell division rates in the epithelium of human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant decrease in cell division rates with age. In contrast, cell division rates did not decrease in the colon of aged mice, and only small decreases were observed in their small intestine or esophagus. These results have important implications for understanding the relationship between normal stem cells, aging, and cancer. Moreover, they provide a plausible explanation for the enigmatic age-dependent deceleration in cancer incidence in very old humans but not in mice.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Envejecimiento / División Celular / Desaceleración / Mutación / Neoplasias Tipo de estudio: Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Animals / Humans / Male Idioma: En Año: 2019 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Envejecimiento / División Celular / Desaceleración / Mutación / Neoplasias Tipo de estudio: Incidence_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Animals / Humans / Male Idioma: En Año: 2019 Tipo del documento: Article