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Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence

2019; National Academy of Sciences; Volume: 116; Issue: 41 Linguagem: Inglês

10.1073/pnas.1905722116

1091-6490

Cristian Tomasetti, Justin Poling, Nicholas J. Roberts, Nyall R. London, Meredith E. Pittman, Michael C. Haffner, Anthony Rizzo, Alex S. Baras, Baktiar Karim, Antônio Kim, Christopher M. Heaphy, Alan K. Meeker, Ralph H. Hruban, Christine A. Iacobuzio‐Donahue, Bert Vogelstein,

Epigenetics and DNA Methylation

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.