Figure 8. Suv39h1 depletion ameliorates progeroid features and extends lifespan in Zmpste24−/− mice.
(a) Continuous passaging assay in MEFs showing extended replicative lifespan in Zmpste24−/− Suv39h1−/− MEFs. Data represent mean±s.e.m., n=3. **P<0.01, two-tailed t-test, Zmpste24−/− Suv39h1−/− versus Zmpste24−/− MEFs. (b) Representative photos of β-galactosidase staining in Zmpste24−/− Suv39h1−/−, Zmpste24−/− and wild-type MEFs. Percentages of β-galactosidase staining-positive cells were shown. Data represent mean±s.e.m., n>200. Compound mutants exhibited significantly reduced percentages of β-galactosidase staining-positive cells (Zmpste24−/− Suv39h1−/− versus Zmpste24−/− MEFs, P<0.05, two-tailed t-test). Scale bar, 200 μm. (c) Representative photo of Zmpste24+/+, Zmpste24−/− and Zmpste24−/− Suv39h1−/− mice showing the partial rescue of body size at 4 months of age. (d) Representative microCT photos in Zmpste24−/− and Zmpste24−/−Suv39h1−/− mice at 4 months of age. (e) Bone volume and bone mineral density of femurs from Zmpste24−/− Suv39h1−/− mice and Zmpste24−/− mice. Data represent mean±s.e.m., n=3. *P<0.05, two-tailed t-test. (f) Body weight of Zmpste24−/− and Zmpste24−/−Suv39h1−/− mice at 4 months of age. Data represent mean±s.e.m., n=12. *P<0.05, two-tailed t-test. (g) Survival rate of Zmpste24−/− and Zmpste24−/− Suv39h1−/− mice. P<0.0001. (h) Maximal lifespan (10% most long-lived animals) in Zmpste24−/− and Zmpste24−/− Suv39h1−/− mice. **P<0.01, two-tailed t-test.