HDAC inhibition mitigates progeroid phenotypes and extends life span of Zmpste24−/− mice. (A) Photograph of Zmpste24+/+, Zmpste24−/−, and NaB-fed Zmpste24−/− at 5 mo of age. (B) Survival and life span of the NaB-fed Zmpste24−/− mice (n = 20) were compared against the untreated controls (n = 22) using the Kaplan–Meir analysis and found to be statistically significant using the log-rank test (**P < 0.01). Fifty-percent survival was observed at 22 and 26 wk for Zmpste24−/− and NaB-fed Zmpste24−/− mice, respectively. (C) Five-month-old Zmpste24+/+, Zmpste24−/−, and NaB-fed Zmpste24−/− mice (n = 5) were scanned using X-ray for bone density analysis. (D) Bone densities were quantified from X-ray scans using ImageJ software (National Institutes of Health). Fold increase in the bone density of NaB-fed mice relative to the untreated Zmpste24−/− control is shown. *P < 0.05 (Student’s t test). (E) Total cell extracts from bone marrow cells (5-mo-old mice) were resolved and Western-blotted with antibodies indicated. (F) Kidney was excised from 5-mo-old Zmpste24+/+, Zmpste24−/−, and NaB-fed Zmpste24−/− mice, cryosectioned, and stained using a SA β-gal assay kit. Blue cells indicate senescence.