Figure 5. Senescent cells promote age-related cardiomyocyte hypertrophy and loss of cardiac stress tolerance.

a, SA-β-Gal stained hearts. Insets show aortic roots (ar) from a transverse plane (arrow marks the aortic root wall) or closups of the ventricular (v) and arterial (a) boxed areas. b, Electron micrographs of X-Gal positive cells in the pericardium (red asterisk marks cilia). Insets show closeups of X-Gal crystals. c, Quantification of cells with X-Gal crystals in the visceral pedicardium (n = 4 mice per treatment). d, Measurements of left ventricle wall thickness (n = 4 mice per group). e, Representative cardiomyocyte cross-sectional images (n = 4 mice per group). f, Quantification of (e). g, Analysis of Sur2a expression in hearts by qRT-PCR (n = 4 mice per group). h, Cardiac stress resistance determined by measuring the time to death after injection of a lethal dose of isoproterenol. i, Change in left ventricular (LV) mass in response to sublethal doses of isoproterenol (10 mg.kg⁻¹) after ten doses administered over 5 days. Scale bars: 1 mm in a; 2 μm (main panel) and 200 nm (inset) in b. Legends in f–h are as in d. Error bars indicate s.e.m. Statistical significance was determined by unpaired two-tailed t test in c, d and f–i. *, P<0.05; **, P<0.01; ***, P<0.001. All mice, except for h, were C57BL/6 ATTAC. +AP, AP-treated mice, –AP, vehicle-treated mice.