Longevity and stress resistance are affected by activation of TOR/Myc in progenitor cells of Drosophila gut

Diverse physiological pathways have been shown to regulate longevity, stress resistance, fecundity and feeding rates, and metabolism in Drosophila. Here we tesed physiological traits in flies with Rheb and Myc- Rheb overexpressed in gut progenitor cells, known as enteroblasts (EBs). We found that activation of TOR signaling by overexpression of Rheb in EBs decreases survival and stress resistance. Additionall, we showed that Myc co-expression in EBs reduces fly fecundity and feeding rate. Rheb overexpression enhanced the level of whole body glucose. Higher relative expression of the metabolic genes dilps, akh, tobi and pepck was, however, observed. The role of TOR/Myc in the regulation of genes involved in lipid metabolism and protein synthesis was established. We showed a significant role of TOR/Myc in EBs in the regulation of the JAK/STAT, EGFR and insulin signaling pathways in Drosophila gut. These results highlight the importance of the balance between all different types of cells and confirm previous studies demonstrating that promotion of homeostasis in the intestine of Drosophila may function as a mechanism for the extension of organismal lifespan. Overall, the results demonstrate a role of TOR signaling and its downstream target Myc in EB cells in the regulation of Drosophila physiological processes

Metformin as geroprotector: experimental and clinical evidence

Apart from being a safe, effective and globally affordable glucose-lowering agent for the treatment of diabetes, metformin has earned much credit in recent years as a potential anti-aging formula. It has been shown to significantly increase lifespan and delay the onset of age-associated decline in several experimental models. The current review summarizes advances in clinical research on the potential role of metformin in the field of geroprotection, highlighting findings from pre-clinical studies on known and putative mechanisms behind its beneficial properties. A growing body of evidence from clinical trials demonstrates that metformin can effectively reduce the risk of many age-related diseases and conditions, including cardiometabolic disorders, neurodegeneration, cancer, chronic inflammation, and frailty. Metformin al

Implications of amino acid sensing and dietary protein to the aging process

Every organism must adapt and respond appropriately to the source of nutrients available in its environment. Different mechanisms and pathways are involved in detecting the intracellular and extracellular levels of macronutrients including amino acids. Detection of amino acids in food sources is provided by taste cells expressing T1R1 and T1R3 type receptors. Additionally, cells of the intestine, pancreas or heart sense amino acids extracellularly. Neuronal and hormonal regulation integrates and coordinates the signals at the organismal level. Amino acid-sensitive mechanisms including GCN2 protein, mTOR and LYNUS machinery adjust cellular process according to the availability of specific amino acids. Triggering these mechanisms by genetic manipulations or by external manipulations with diet

mTOR pharmacology

The mammalian target of rapamycin (mTOR) signaling pathway is a crucial mechanism for nutrient sensing and regulation of growth, development, and homeostasis. Dysregulation of mTOR is involved in a number of chronic conditions including obesity, type 2 diabetes, cancer, and neurodegenerative disorders. mTOR signaling is modulated by a variety of factors, including nutrient and oxygen availability, growth factors, and insulin. This evolutionary conserved pathway also plays an important role in aging and lifespan regulation. All of these involvements in central metabolic functions make mTOR an interesting target for pharmacological manipulation. In humans, rapamycin has been approved for use since 1999 and is prescribed for immunosuppression in transplant recipients or as an anticancer agent. Rapamycin and rapalogs have shown beneficial effects in health- and lifespan prolongation in model organisms and patient data from clinical trials has also provided some promising results in the suppression or prevention of age-related diseases. In this article, we analyze current evidence and discuss the potential role of mTOR-inhibitors and mTOR-activators in the battle against aging and age-related diseases