Hematopoietic stem cell performance and identity, crucial for homeostasis of the blood-forming system, is governed by extrinsic factors found in the bone marrow microenvironment. Communication within hematopoietic stem cell niches occurs via soluble factors or cell-to-cell contacts between niche and blood-forming cells - which in turn are influenced by systemic factors distributed by the bone marrow extracellular fluid. Although hematopoietic cell-intrinsic aging contributes to the aging phenotype of the hematopoietic system, the architecture and cellular composition of the bone marrow microenvironment have emerged to be highly dynamic during aging and suggested as a major driver for the functional limitations of the blood system observable in old individuals. Recent attention has been paid to the interface between the peripheral nervous system and blood-forming cells in the bone marrow in several clinical contexts and in aging - the latter is reviewed here.
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