HSC inflammaging model. Aging is associated with increased microbial compounds in blood because of increased permeability of the intestinal barrier. Blood-derived microbial compounds stimulate pattern recognition receptors. Multiple BM cells stimulated via pattern recognition receptors release IL-1a and IL-1b. IL-1–induced signaling imprints myeloid bias on HSCs. Myeloid-biased HSCs accumulate with age and increase their myeloid cell output. Myeloid cells produce higher and more sustained IL-1a and IL-1b upon LPS stimulation, thus sustaining an HSC inflammaging process. Microbiota IL-1–dependent onset of a myeloid-differentiation bias in HSCs during physiological aging can be substantially reverted by treatment with antibiotics or IL-1 antagonists.