Mikhail Blagosklonny and Zoya N. Demidenko

At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence Here we demonstrated that, at cytostatic, near-toxic concentrations, resveratrol inhibited S6 phosphorylation and prevented the senescence morphology in human cells. Using a sensitive functional assay, we found that resveratrol partially prevented loss of the proliferative potential associated with cellular senescence. Resveratrol was less effective than rapamycin, because aging-suppression by resveratrol was limited by its toxicity at high concentrations. We discuss whether concentrations of resveratrol that inhibit mTOR (target of rapamycin) and suppress cellular senescence are clinically achievable and whether partial inhibition of mTOR by resveratrol might be sufficient to affect organismal aging.  https://www.researchgate.net/scientific-contributions/39445053_Zoya_N_Demidenko oncotarget impact factor 2020 Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the O...

Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium Abstract Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendipitously, we found that insulin failed to induce the HIF-1α-dependent response, when RPE cells were cultured in Dulbecco's modification of Eagle's medium (DMEM). Whereas concentration of glucose in MEM corresponds to normal glucose levels in blood (5.5 mM), its concentration in DMEM corresponds to severe diabetic hyperglycemia (25 mM). Addition of glucose to MEM also caused IR. Glucose-mediated IR was characterized by basal activation of mTORC1 and its poor inducibility by insulin. Basal levels of phosphorylated S6 kinase (S6K), S6 and insulin recept...