Dioprotective effects of autophagy inducing drug, chloramphenicol113, 114. Within the rat myocardial infarction model, blocking autophagy by use of bafilomycin led to exacerbated cardiac dysfunction115. In another study, glucose deprivation or ischemia induced autophagy helped to promote cell survival110. Also intermittent fasting, an intervation recognized to induce SIRT1, helped to reduce infarct size by 2 fold within the rat myocardial infraction model116. According to these reports it seems that increased autophagy is often a physiological or pathologicalCirc Res. Author manuscript; readily available in PMC 2015 January 17.Pillai et al.Pageresponse to promote myocardial cell survival largely is determined by the nature and extend on the cellular stress.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptA direct function of sirtuins other than SIRT1 within the regulation of autophagy will not be studied so far. But PTEN Synonyms evidence suggests that autophagy may very well be associated with increased activation of SIRT6, because the transcriptional factors, NFkB and AP1, whose activity is negatively regulated by SIRT6, are shown to become positive regulators of autophagy117, 118. Concerning the attainable connection of sirtuins with Akt, recent reports show that chronic Akt activation worsens aging-induced cardiac hypertrophy and myocardial contractile function by means of loss of autophagic regulation119. Further studies making use of cardiomyocytes are required to elucidate the situations where sirtuins and Akt crossover to regulate autophagy.Sirtuins, Akt and AgingCalorie restriction is the only verified method to lessen the aging process1. Both, SIRT1 and IGF/Akt signaling pathways are regulated by nutrition supply and each pathways are recommended to become involved in regulation of lifespan in numerous organisms. Numerous reports suggest that the health advantages of calorie restriction are mediated through activation of sirtuins; however a role of SIRT1 within this process is disputed. SIRT1 knockout mice failed to increase physical activity in the course of calorie restriction120. Also, calorie restriction exacerbated the decreased survivability of SIRT1 null mice, suggesting a positive role of SIRT1 in mediating effects of calorie restriction121. In contrast, over expression of SIRT1 didn’t extend replicative lifespan of human fibroblasts or prostrate epithelial cells, rather Androgen Receptor Inhibitor Formulation caused replicative senescence in response to cellular stress7, 122. Also calorie restriction and/or mutations inside the yeast Akt homologue; Sch9 causes dramatic chronological lifespan extension in yeast lacking Sir2123. Among the family members of transcription factors whose activity is regulated by SIRT1 and which play a function in the aging process is Foxo124, 125. Consistent with all the ambiguous role of SIRT1 in lifespan extension, SIRT1 can positively and negatively regulate activity from the Foxo family of factors. SIRT1 activates Foxo1 and Foxo3 by deacetylation, which promotes nuclear localization of those factors126, 127. Contrary to this, SIRT1 also can hamper Foxo3a activity by generating it a target for skp2-mediated ubiquitination and degradation128. Within this course of action Akt can synergies with SIRT1 by phosphorylating Foxo isoforms which prevents their translocation towards the nucleus, thereby abolishing their transcriptional function129. In our research we discovered that SIRT1-mediated deacetylation positively regulates the activity of Akt upon development aspect stimulation of cells9. We consequently propose that in the presence of growth (insulin) signaling, SIRT1 activates.