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 the Table). 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 2 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 was administered at ≈9 months of age, and electrocardiography was performed at the indicated ages (n=7–10 oil; n=11 or 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 euthanized at 14.5 months of age (n=5 or 6 oil; n=11 tamoxifen). A group of age-matched untreated wild-type (WT) mice was included for comparison (n=7–9). Scale bar, 50 µm. Data are mean±SEM. Differences were analyzed by 1-way ANOVA and the post hoc Tukey test. **P<0.01; ***P<0.001; ****P<0.0001. Each symbol represents 1 animal. A indicates adventitia; L, lumen; and M, media.