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

• DOI: 10.1073/pnas.1905722116
• Publication Date: 2019-09-24T00:34:31Z
• Authors: Cristian Tomasetti; Justin Poling; Nicholas J. Roberts; Nyall R. London; Meredith E. Pittman; Michael C. Haffner; Anthony Rizzo; Alex Baras; Baktiar Karim; Antonio Kim; Christopher M. He...; Alan K. Meeker; Ralph H. Hruban; Christine A. Iaco...; Bert Vogelstein
• Keywords: Adult; Aged, 80 and over; Male; Aging; 0303 health sciences; Colon; Duodenum; Deceleration; Incidence; 3. Good health; Mice, Inbred C57BL; Mice; Young Adult; 03 medical and health sciences; Esophagus; Ki-67 Antigen; Neoplasms; Mutation; Paranasal Sinuses; Animals; Humans; Cell Division; Aged

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.