Background: While many studies have investigated the metabolic and cellular effect of the AMPK activator anti-diabetic drug metformin, we have not come across a paper that deals with the molecular mechanism of its anti-aging impact via irisin hormone in a SIRT1/ PPAR-γ-dependent manner. Materials and Method: For this purpose, we conducted, besides the control group, an experimentally induced aging model through D-galactose and compared its solo effect versus the combined metformin and D-galactose administration. Furthermore, another group pretreated by Bisphenol-A-diglycidyl ether (BADGE), a selective PPAR-γ antagonist, was conducted. Results: Metformin blunted aging-associated hepatocellular changes in both structural and functional aspects as revealed by biochemical and histopathological evaluations. Also, it maintained glucose homeostasis. Such effects were accompanied bypreserving redox homeostasis and boosting the level ofIrisin andSIRT1proteins. A mechanism that was, in part, dependent on PPAR-γ as evidenced after its blockade by BADGE. There was an observable negative correlation between serum irisin and ALT, HOMA-IR, and MDA while a positive correlation with total antioxidant capacity (TAC). Conclusion: The results came up with the geroprotective impact of metformin and its benefits could extend far beyond diabetes. It appears to be a promising anti-aging pill. It could retard aging-associated hepatic alterations and/or its bad consequences progression. |
