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Within the adult central nervous system (CNS) of most mammals resides a resident stem cell population, known as neural stem cells (NSCs). NSCs are located within specific niches of the CNS and maintain a self-renewal and proliferative capacity to generate new neurons, astrocytes, and oligodendrocytes throughout adulthood. The NSC niches are dynamic and active environments that are within proximity to the systemic circulation and the cerebrospinal fluid (CSF). Therefore, NSCs respond not only to factors present in the local microenvironment of the niche but also to factors present in the systemic macroenvironment. The factors can be soluble forms such as cytokines and chemokines located in the circulation or directly from local cells, such as microglia and astrocytes. Additionally, recent evidence points towards physiological aging and its association with a progressive loss of function and a decline in the self-renewal and regenerative capacities of CNS NSCs, which can be further exacerbated by changes in the local and systemic milieu. This review will highlight the main intrinsic and extrinsic regulators of neural stem cell function under homeostatic and inflammatory conditions including those trafficked within extracellular membrane vesicles. Further, discussion will center around how intrinsic and extrinsic factors impact normal homeostatic functions within the adult brain and in aging. [ABSTRACT FROM AUTHOR]