Aging of the hematopoietic stem cell niches

Abstract

Adult hematopoietic stem cells (HSCs) reside in the bone marrow (BM) and provide the basis to fulfill the hematopoietic needs of an organism. Their properties of self-renewal and multilineage differentiation are controlled by direct interaction witha specific microenvironment-the so-called stem cell ‘niche’. Conceptual advances in our understanding of the composition of the HSC compartment suggest that changes in the BM HSC microenvironment may reflect the aging process. The balance and extent of the effect of intrinsic versus extrinsic (environment) changes during aging on HSC are still under investigation. Growing evidence suggests that the BM HSC niche is very important in the regulation of cellular aging of HSCs. A young HSC niche would act as a protective environment, preventing HSC DNA damage, as well as replicative senescence throughprotection from radicals and toxic compounds, and prevention/amelioration of aging-associated signaling pathways resulting in epigenetic/genetic modifications, hematopoietic impairments, and cancer predisposition. To what extent the aging of the niche contributes to the “HSC aging” phenotype remains unknown. The analysis of the effect of aging on the activity of these specialized cell “niches” and their molecular products is the focus of this chapter.