Senescence And Epithelial-mesenchymal Transition Of Aging Kidney Were Alleviated By Shotr-term Caloric Restriction And Caloric Restriction Mimetics Via AMPK-mTOR Signaling

Background: It is well known that either cell senescence orepithelial-mesenchymal transition (EMT) can be served as a independent riskof declining renal function. Some evidences about caloric restriction (CR) andcaloric restriction mimetics (CRM) alleviated cell senescence and EMT havebeen accumulated, but hardly study focused on the function and mechanism ofthem on cell senescence and EMT of aging kidney.Methods: All involved male SD rats were divided into4groups. YAL:3-mon-old, ad libitum; OAL:25-mon-old, ad libitum; OCR:25-mon-old,caloric given was60%of OAL’s; OMET:25-mon-old, ad libitum, weretreated with metformin at300mg/kg/d.8weeks later, all rats were sacrificed.Human primary proximal tubular cells (PTC) were isolated from normal kidneytissue. High glucose (HG) was used to induce senescence and EMT. Metforminor resverotrol and HG were used to co-stimulate PTC to explore the effect ofthem on senescence and EMT. SiRNA technique on AMPK was used to testthe function of AMPK-mTOR signaling in the process. Western Blot,Senescence-associated-β-galactosidase staining and Senescence-associatedfocal heterochromatin etc. were used to evaluate the related variation.Results: Short-term CR and metformin treated alleviated age-relatedhypertriglyceridemia and proteinuria. Short-term CR and CRM treatedalleviated age-related and HG-induced EMT and cell senescence of kidney,accompanying by activated AMPK-mTOR signaling, which decreased with ageor when exposed to HG. When AMPK was silenced, overexpressed mTOR andaggravated senescence&EMT of PTC were detected, but can’t be alleviated by CRM.Conclusion: Short-term CR and metformin treated alleviated age-relatedhypertriglyceridemia and proteinuria. HG can induce senescence and EMT ofPTC. CR and CRM alleviated cell senescence and EMT of kidney viaAMPK-mTOR signaling.