TY - JOUR
T1 - Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence
AU - Tomasetti, Cristian
AU - Poling, Justin
AU - Roberts, Nicholas J.
AU - London, Nyall R.
AU - Pittman, Meredith E.
AU - Haffner, Michael C.
AU - Rizzo, Anthony
AU - Baras, Alex
AU - Karim, Baktiar
AU - Kim, Antonio
AU - Heaphy, Christopher M.
AU - Meeker, Alan K.
AU - Hruban, Ralph H.
AU - Iacobuzio-Donahue, Christine A.
AU - Vogelstein, Bert
N1 - Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019/10/8
Y1 - 2019/10/8
N2 - 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.
AB - 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.
KW - Aging
KW - Cancer
KW - Cell division
KW - Mutation rate
UR - http://www.scopus.com/inward/record.url?scp=85073074552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073074552&partnerID=8YFLogxK
U2 - 10.1073/pnas.1905722116
DO - 10.1073/pnas.1905722116
M3 - Article
C2 - 31548407
AN - SCOPUS:85073074552
SN - 0027-8424
VL - 116
SP - 20482
EP - 20488
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -