Research Article: Aging-Associated Changes in Hematopoiesis and Leukemogenesis: What’s the Connection?

Date Published: June 2, 2011

Publisher: Impact Journals LLC

Author(s): Curtis J. Henry, Andriy Marusyk, James DeGregori.

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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.

Partial Text

The proportion of elderly people is progressively rising throughout the world, with the most pronounced increase in the developed world. Elderly people (>65 years old) are expected to comprise greater than 20% of the world’s human population by 2050 [1]. This increase is posing major challenges for healthcare systems, as aging is associated with marked increases in a number of diseases, including most types of cancers [2-4]. With more than 80% of human cancers being diagnosed after the age of 50 [5], aging represents the single most important prognostic factor for many cancers, including lung, breast, colon, prostate, and certain leukemias [3, 6, 7].

The increasing proportion of elderly people in populations worldwide and associated increases in rates of cancers pose substantial challenges to biomedical research and medical care, making the task of deciphering mechanisms linking the two a top priority. Since cancer is generally considered a disease of the elderly, a more comprehensive understanding of how aging alters cellular function, and how alterations in cells and tissues impact on carcinogenesis, should contribute to the development of more efficacious therapeutic and prevention strategies for cancer [112]. Studies in mice and humans have revealed that aging is characterized by drastic reductions in immune cell function, which subsequently leads to decreased immune surveillance. This immunocompromised state has mainly been attributed to alterations in HSC and hematopoietic development (and in some cases cell numbers), and aging-associated thymic involution. Deficiencies in these compartments result in reduced myeloid and lymphocyte cellular functions and decreased T and B cell diversity in the periphery. Importantly, aging is also associated with increased incidence of many cancers, including hematopoietic malignancies, and in this review we have discussed the many possible connections between aging and cancers.

 

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