Peanut Procyanidin A Delays Hematopoietic Stem Cells Aging through Cox5a.

Hematopoietic stem cells (HSCs) are essential for maintaining blood system homeostasis. Their aging leads to functional decline and increased susceptibility to blood disorders, largely driven by elevated reactive oxygen species (ROS). Here, we identify peanut procyanidin A (PPA) as a potent compound that delays HSC aging by targeting cytochrome c oxidase subunit 5a (Cox5a). Through screening of 234 FDA-approved natural compounds, we found that PPA significantly reduces mitochondrial ROS and improves the function of aged HSCs in mice. Transcriptomic analysis revealed that PPA induces a metabolic shift from oxidative phosphorylation toward glycolysis, reminiscent of a youthful HSC state. Moreover, PPA rescues aging phenotypes in human CD34+ hematopoietic progenitor cells. Our study establishes Cox5a as a druggable target for HSC rejuvenation and highlights PPA as a promising therapeutic candidate for age-related hematopoietic decline.