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

Abstract

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.

Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors

“…with EdU (2 mg/mouse, to limit the expansion of oncogenically initiated progenitors). Notably, hematopoietic malignancies of the B lineage predominate in older mice, while in elderly humans, both B lymphoid and myeloid leukemias are common (63,64). B lymphoid leukemias are also common in young children, and infections and the associated inflammation have been proposed to play a role in their development (65).…”

Rapalogs in cancer prevention

“…Growth-limiting conditions and senescence of normal cells provides such a selective advantage. [94][95][96][97] Therapy further drives tumor progression.…”

Dysregulation of the mTOR pathway in p53-deficient mice

“…21,22,36 Senescent microenvironment favors cancer. [37][38][39][40][41][42][43][44][45][46] Noteworthy, overexpression of p53 under physiological regulation increases lifespan and decreases cancer incidence. 47 Cancer is an age-related disease and its incidence increases exponentially with age.…”