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

Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20482-20488. doi: 10.1073/pnas.1905722116. Epub 2019 Sep 23.

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.

Keywords: aging; cancer; cell division; mutation rate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Animals
  • Cell Division*
  • Colon / cytology
  • Colon / metabolism
  • Deceleration*
  • Duodenum / cytology
  • Duodenum / metabolism
  • Esophagus / cytology
  • Esophagus / metabolism
  • Humans
  • Incidence
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation*
  • Neoplasms / epidemiology*
  • Neoplasms / pathology
  • Paranasal Sinuses / cytology
  • Paranasal Sinuses / metabolism
  • Young Adult

Substances

  • Ki-67 Antigen