Figure 7. Ubiquitous progerin suppression and lamin A restoration extends lifespan in both mildly and severely symptomatic HGPSrev-Ubc-CreER^T2 mice.

(A) Experimental protocol for studies with HGPSrev-Ubc-CreER^T2 mice, showing the age at which oil or tamoxifen administration started (details in Table 1). (B) Oil or tamoxifen were administered at ≈6 months (LEFT: n=18 Oil and n=22 Tamoxifen) or ≈13 months (RIGHT: n=7-20 Oil and n=9-23 Tamoxifen). The graphs show the results from two independent experiments. Differences were analyzed by unpaired multiple t-tests and the Holm-Sidák correction in body-weight studies and by the Mantel-Cox test in Kaplan-Meier survival curves. (C) Oil or tamoxifen were administered at ≈9 months of age, and electrocardiography was performed at the indicated ages (n=7-10 Oil; n=11-12 Tamoxifen). Data are medians with interquartile range±minima and maxima. Differences were analyzed by mixed-effects analysis with the Geisser-Greenhouse correction and Sidák’s multiple comparisons test. (D) Hematoxylin & eosin (H&E) and Masson’s trichrome staining of aortic cross-sections from mice receiving oil/tamoxifen at ≈9 months and sacrificed at 14.5 months of age (n=5-6 Oil; n=11 Tamoxifen). A group of age-matched untreated WT mice was included for comparison (n=7-9). Scale bar, 50 μm. Data are mean±SEM. Differences were analyzed by one-way ANOVA and the post-hoc Tukey test. **, p<0.01; ***, p<0.001; ****, p<0.0001. Each symbol represents one animal. A, adventitia; L, lumen; M, media.