Figure 7.

The recovery SIRT1 levels in aged hearts rescue AMPK signalling and resistance to ischemic stress. (A) Immunoblotting showed the recovery of SIRT1 expression levels in aged hearts by coronary delivery of AAV9-Sirt1. (B) Immunoblotting showed that the coronary delivery of AAV9-Sirt1 significantly rescues the ischmic AMPK phosphorylation in the aged hearts. (C) Echocardiography showed that recovery of impaired SIRT1 levels in the aged hearts improved the resistance of aged heart to ischemic stress as shown by ejection fraction (EF) and fractional shortening (FS). Values are means ± SEM, n = 4–6, *P < 0.05 vs. Sham, respectively; ^†P < 0.05 vs. young I/R; §P < 0.05 vs. aged I/R using 2-way ANOVA with Tukey’s post-test. (D) Young, aged, and aged + AAV9-Sirt1 mice were subjected to in vivo regional ischaemia 45 min followed by 24-h reperfusion. Upper: representative sections of the extent of myocardial infarction; Lower left: ratio of the area at the risk (AAR) to the total myocardial area; Lower right: ratio of the infarcted area (INF) to AAR. Values are means ± SEM, n = 5–6, *P < 0.05 vs. young, ^†P < 0.05 vs. aged using 2-way ANOVA with Tukey’s post-test. (E) Glucose oxidation and (F) Oleate oxidation in the isolated working heart and (G) relative percentage of ATP production from glucose and oleate oxidation. After balancing 20 min, isolated hearts were subjected to 10 min of ischaemia and 20 min of reperfusion. Glucose oxidation was analysed by measuring [¹⁴C] glucose metabolism into ¹⁴CO₂. Oleate oxidation was measured by the incorporation of [9,10-³H₂O] oleate into ³H₂O. Values are means ± SEM, n = 4–5, *P < 0.05 vs. basal, respectively; ^†P < 0.05 vs. young I/R; §P < 0.05 vs. aged I/R using 2-way ANOVA with Tukey’s post-test.