Metabolism of Young and Aged Hematopoietic and Acute Myeloid Leukemia Stem Cells: Insights for Rejuvenation and Therapy

Hematopoietic stem cells (HSCs) reside in the adult bone marrow and sustain the lifelong production of blood and immune cells. The processes of HSC quiescence, activation, and aging are complex and are orchestrated by a combination of intrinsic and extrinsic stimuli. Similarly, leukemic stem cells (LSCs) are responsible for the initiation of leukemia and drug resistance. Metabolic adaptations are critical for these processes, and research in this area is rapidly evolving. In this review, the metabolic programs, including glycolysis, mitochondrial metabolism, and amino acid and lipid metabolism, of young HSCs, aged HSCs, leukemia blasts, and LSCs are comparatively presented, with a greater focus on aged HSCs and LSCs, as aging and leukemia represent substantial health challenges. The clinical implications of metabolic vulnerabilities, either for rejuvenating aged HSCs or selectively killing LSCs, are also discussed.