title: Loss of cardioprotection with ischemic preconditioning in aging hearts: role of sirtuin 1?
abstract: The effectiveness of ischemic preconditioning (IPC) to protect the heart against ischemia/reperfusion injury (IRI) declines with age. The deacetylase protein sirtuin 1 (Sirt 1) confers myriad functions including longevity and cardioprotection against IRI. As such, Sirt 1 may be a potential candidate to explain the protective effect of IPC. We aim to explore the role of Sirt 1 in the loss of the cardioprotective effect of IPC with age. Isolated hearts from young (9 weeks) and older (12-18 months) Long-Evans rats were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Preconditioning stimuli were applied with either 2 cycles of 5-minute ischemia/reperfusion or with the potent Sirt 1 agonist resveratrol (RSV, 10 µmol/L) for 15 minutes followed by a 10-minute washout before the sustained ischemia. Both IPC and RSV significantly enhanced the functional recovery of young hearts by 168% (P < .001 vs control) and 65% (P < .01 vs control), respectively, and concomitantly reduced the infarct size by 65% and 45%, but the effect was blunted in older hearts. Administration of the selective Sirt 1 inhibitor III to young hearts did not alter the protective effect of IPC. Following ischemia/reperfusion, higher Sirt 1 deacetylase activity was detected in older hearts compared to young hearts (0.48 ± 0.13 arbitrary units [AU] vs 0.17 ± 0.03 AU, P < .01) and IPC did not alter Sirt 1 deacetylase activity. In conclusion, although Sirt 1 deacetylase activity is increased with age during ischemia/reperfusion, our data suggest that the loss of the cardioprotective effect of IPC in older animals is likely to be independent of Sirt 1.
authors.affiliation: Department of Medicine, Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, Cape Town, South Africa. tasneem.adam@uct.ac.za
authors.forename: Tasneem
authors.initials: T
authors.lastname: Adam
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sharp
authors.forename: Lionel H
authors.initials: LH
authors.lastname: Opie
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lecour
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D051381:Rats; D020318:Rats, Long-Evans; D056564:Sirtuin 1 / Q000502:physiology*
chemical_list: D056564:Sirtuin 1