Stem cells, aging, and cancer: inevitabilities and outcomes.
Given the unique abilities of a stem cell to self-renew, differentiate, and proliferate, it is no wonder that they are critically important to an organism during development and to maintain homeostasis. Likewise, when something goes awry within a stem cell, it is likely to have far-reaching effects, since stem cells persist throughout the lifetime of the individual. Two significant biological phenomena that involve stem cells are the inevitable process of aging and a major health issue whose incidence increases with aging: cancer. In this review, we summarize evidence and theories concerning these two stem cell processes. The inability of stem cells to be passaged indefinitely in mice and the data supporting regular replication of the quiescent stem cell pool are discussed. Further, the current evidence indicating a stem cell origin of acute myeloid leukemia, including examples from both experimental mouse models and human clinical samples, is evaluated. Finally, we propose a model in which aging of the stem cell population of the hematopoietic system in particular can create conditions that are permissive to leukemia development; in fact, we suggest that aging is a secondary event in leukemogenesis.
Bell
Deborah R
DR
Department of Internal Medicine, Markey Cancer Center, University of Kentucky, Lexington 40536-0093, USA.
Van Zant
Gary
G
D000208:Acute Disease; D000375:Aging / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured / Q000166:cytology / Q000637:transplantation; D016922:Cellular Senescence; D018450:Disease Progression; D005544:Forecasting; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D011828:Radiation Chimera; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
D018398:Homeodomain Proteins