Research Perspective Volume 3, Issue 6 pp 643—656

Aging-Associated Changes in Hematopoiesis and Leukemogenesis: What's the Connection?


Figure 2. Conventional and Adaptive Oncogenesis Models for Tumorigenesis. Conventional View (top): Aging primarily contributes to increased cancers by facilitating the accumulation of oncogenic mutations (red cells), including activating mutations in oncogenes or genetic/epigenetic inactivation of tumor suppressor genes. Adaptive Oncogenesis Model (bottom): The ability of an oncogene to induce cancer is context specific. In a healthy population, the ability of cells to effectively compete for niche space is high due to optimal progenitor cell fitness. Thus, this competition is inherently tumor suppressive. However, if cellular fitness decreases as a result of aging or environmental insults, the acquisition of an oncogenic mutation could be adaptive due to its ability to correct or circumvent defective cellular function. In this context, these cells would be selected for leading to carcinogenesis (oncogenically mutated and cancer cells are shown in red).