Hematopoietic Stem Cell Metabolism during Stress and Aging

Hematopoietic stem cells (HSCs) support the lifelong production of blood but undergo substantial changes during aging. Aging causes a progressive decline in the repopulation ability of HSC with changes in the proportion of myeloid and lymphoid lineages. Metabolic remodeling is increasingly recognized not only as a consequence of HSC aging but also as an active contributor to age-associated changes in HSC function. Quiescent HSCs have low metabolic activity, in contrast with their highly proliferative progeny. During regeneration, drastic metabolic remodeling enables HSC to exit quiescent and proliferate to sustain blood production for emergency hematopoiesis. Metabolic activity drifts during aging. Changes in glycolysis, mitochondrial activity, and lysosomal functions all contribute to a slow decline of the hematopoietic system. In this review, we focus on the metabolic needs of HSCs, how they control their quiescence and proliferation, and how a metabolic drift contributes to HSC aging.