Research Perspective Volume 3, Issue 6 pp 643—656
Aging-Associated Changes in Hematopoiesis and Leukemogenesis: What's the Connection?
- 1 Department of Biochemistry and Molecular Genetics, Integrated Department of Immunology, Department of Pediatrics, Program in Molecular Biology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
- 2 Department of Medical Oncology, Dana Farber Cancer Institute; Department of Medicine, Harvard Medical School, Boston, MA, USA
Received: June 20, 2011 Accepted: June 27, 2011 Published: July 2, 2011https://doi.org/10.18632/aging.100351
How to Cite
Aging is associated with a marked increase in a number of diseases, including many types of cancer. Due to the complex and multi-factorial nature of both aging and cancer, accurate deciphering of causative links between aging and cancer remains a major challenge. It is generally accepted that initiation and progression of cancers are driven by a process of clonal evolution. In principle, this somatic evolution should follow the same Darwinian logic as evolutionary processes in populations in nature: diverse heritable types arising as a result of mutations are subjected to selection, resulting in expansion of the fittest clones. However, prevalent paradigms focus primarily on mutational aspects in linking aging and cancer. In this review, we will argue that age-related changes in selective pressures are likely to be equally important. We will focus on aging-related changes in the hematopoietic system, where age-associated alterations are relatively well studied, and discuss the impact of these changes on the development of leukemias and other malignancies.
Organismal fitness: a measure of reproductive success (the ability of an organism to pass its genes on to future generations of that organism).; Cell fitness: a measure of the ability of stem/progenitor cells of a certain epigenotype/genotype to pass this type on to subsequent cell generations. For discussions here, we are concerned with the fitness of cells that maintain replicative potential. Cell fitness is in some ways a relative parameter, and dependent on the fitness of competing cells. Thus, the relative representation of a particular clone within a progenitor cell pool is proportional to its fitness. On the other hand, the fitness of stem and progenitor cells should also be comparable across individuals of different ages or genotypes, even if measurement of this relative fitness requires that these cells be placed in competition, such as following transplantation into a common host.; Adaptive: increases fitness (e.g. a mutation that increases cellular fitness would be adaptive).; Mutation: we will often refer to heritable epigenetic and genetic mutational changes generally as “mutations”.; Adaptive landscapes: the potential epigenetic and genetic changes that could alter the fitness of a cell population..