Dual targeting of the antagonistic pathways mediated by Sirt1 and TXNIP as a putative approach to enhance the efficacy of anti-aging interventions

摘要: The organism's ability to regulate oxidative stress and metabolism is well recognized as a major determinant of longevity. While much research interest in this area directed towards the study genes that inhibit and/or improve metabolism, contribution aging process with antagonistic effects on these two pathways still less understood. present investigated respective roles histone deacetylase Sirt1 thioredoxin binding protein TXNIP, opposite mediating action putative anti-aging interventions. Experiments were carried out vitro vivo determine effect proven, limited calorie availability, unproven, resveratrol dehydroepiandrosterone (DHEA), expression TXNIP. results indicated availability consistently inhibited TXNIP cancer normal cells including stem cells, however, it only slightly induced Sirt1expression cells. In contrast, had biphasic effect, DHEA tissue specific manner, both vivo. Whereas all three approaches tested through glycolytic pathway, acted by inhibiting G6PD activation AMPK. light previous reports induces AMPK-mediated signaling our findings point possibility negative relationship between that, if validated, can be exploited efficacy