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

Author:

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

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.

Funder

The John Templeton Foundation

The Maryland Cigarette Restitution Fund

NCI

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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