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. 2018 Dec 21;9:5435. doi: 10.1038/s41467-018-07825-3

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Treatment with ABT-737 counteract accelerated aging process of Prf1^−/− male mice. a Starting from 18 months, ABT-737 or vehicle were administered to Prf1^−/− mice at the beginning of each month, the mice were analyzed at the age of 20 months. b Change in distance run on a voluntary exercise test. Values are means and dashed lines represent ± SEM for each curve (n = 5 mice per group). c Average voluntary exercise levels during the last 3 days of the two months (n = 5 mice per group). d SA-β-Gal activity in indicated organs. Scale bar, 100 µm. (n = 5 mice per group). e CD45⁻/SA-β-Gal + /HMGB1⁻ population in indicated organs (n ≥ 4 mice per group). f Relative cytokine levels in the serum for top five altered cytokines. Bars represent average intensity of 3 pooled samples. g WBC counts. (n = 5 mice per group). h Spleen weights. (n = 3 mice per group). i Flow-cytometry quantification of total immune cells (CD45⁺), T cells (CD45⁺/CD3⁺/NK1.1^-), NKT cells (CD45⁺/CD3⁺/NK1.1⁺), and NK cells (CD45⁺/CD3^-/NK1.1⁺) in indicated organs (n ≥ 4 mice per group). j Fibrotic areas in indicated organs based on the Sirius Red-stained sections in Supplementary Figure 6b. (n = 5 mice per group). Student’s t-test was used for all comparisons between Prf1^−/− mice and WT mice. k Differentially expressed genes in indicated organs. Notable enriched GO terms are highlighted (n ≥ 3 mice per group). l SASP genes score, presented as expression mean log ratio of old ABT-737 and Vehicle treated over young Prf1^−/− mice (Supplementary Figure 6c). The bottom panel depicts number of detected SASP genes. (n ≥ 3 mice per group). m Upper panel: Euler diagram of differentially expressed genes from all analyzed tissues. Lower panel: Log ratio of gene expression for 20-months-old ABT-737 (y axis) and Vehicle (x axis)-treated over young Prf1^−/− mice. Dashed line represents linear regression fitted to the data; p value computed against the null hypothesis that tilt = 1; (n ≥ 3 mice per group). For all graphs, values are means ± SEM. Student’s t-test was used for all other comparisons. (*P < 0.05, **P < 0.01, ***P < 0.001)