The aging hematopoietic stem cell niche

Abstract Hematopoietic stem cells (HSC) undergo significant changes during aging, which culminate in an expansion of the stem cell pool, loss of regenerative potential and alterations in lineage differentiation that is skewed toward myeloid cells. While cell intrinsic factors such as DNA damage, dysregulation of epigenetic stability and dysfunction of autophagy/mitophagy processes have all been implicated in HSC aging, the role of the bone marrow (BM) microenvironment or stem cell niche is also a key contributor to the deterioration of HSC with age. The cellular components that comprise the niche such as megakaryocytes, endothelial cells, mesenchymal stromal cells, osteoblasts and adipocytes all undergo functional changes that either directly or indirectly influence HSC. In addition, imbalance of the extracellular components of the aging microenvironment including cytokines, matrix molecules as well as dietary nutrients have also been associated with distinct regulatory roles in HSC fate during aging. This chapter will review the recent advances in our understanding of how the aging microenvironment contributes to HSC dysfunction and the mechanisms that may be potentially targeted for restoring the functional potential of aged HSC.