Genetic and pharmacologic blockage of IL-1–IL-1R1 signaling reduces Tet2^+/−clonal expansion during aging. (A) Experimental design. (B) Longitudinal quantification of the percentage of donor-derived peripheral blood (PB) CD45.2⁺ cells from indicated genotypes: WT; WT, WT; Ilr1^–/–, Tet2^+/−; WT and Tet2^+/−; Ilr1^–/–, over 9 months after transplantation (n = 4-6). (C) Fold variation (within 7- to 9-month period) in the percentage of donor-derived PB CD45.2⁺ cells from indicated genotypes. (D) Terminal assessment of the percentage of donor-derived BM populations from indicated genotypes. (E) Experimental design. (F) Longitudinal quantification of the percentage of CD45⁺ WT ZsG⁺ and CD45⁺Tet2^+/− ZsG⁺ in PB of mice exposed to PBS or anakinra treatment (hIL1ra) (n = 3-5). (G) Fold variation (within 11-13 months) in the percentage of CD45⁺ WT ZsG⁺ and CD45⁺Tet2^+/− ZsG⁺ cells in PB of mice exposed to PBS or hIL1ra (n = 3-5). (H) Percentage of WT ZsG⁺ and Tet2^+/− ZsG⁺ on indicated BM populations after PBS or anakinra treatment (n = 3-5). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, and ∗∗∗∗P < .0001 by unpaired t-test (within the same genotype; D and H) or by a 1-way analysis of variance with Tukey correction (last time point on B, C, F, and G). Error bars represent standard error of the mean. ns, not significant; WBM, whole bone marrow.