Myelodysplasia, Clonal Hematopoiesis, and Aging

Asking whether an age-associated disease is a part of normal aging is an exercise in boundary drawing. The very definition of an age-related disease as something distinct from aging is the result of past boundary drawing. Many of these boundaries are quite arbitrary. Aging is a complex phenomenon, and people like to lay taxonomies on top of a complex space of many interacting mechanisms in order to try to make some sense of it. The results are sometimes helpful, sometimes not. The discussion in this open access paper is perhaps a good example of where the exercise of drawing boundaries can lead, while trying to separate out categories from the interplay of cancer, precancerous processes, and mechanisms of aging. Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders characterized by ineffective hematopoiesis resulting in peripheral blood cytopenias. MDS typically occur at an advanced age with a median age at diagnosis of 68 to 75 years. MDS as clonal disorders may be preceded by a state of clonal hematopoiesis (CHIP) in which MDS defining features cannot (yet) be substantiated. Whereas CHIP-specific somatic mutations are rarely detected in persons younger than 40 years, they reveal an increasing incidence with advanced age. Considerable progress has been made in deciphering the biology of normal aging, which includes the distinction of normal aging from pathologies associated with aging; additional progress has been made in describing MDS prece...
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