Investigating the Mechanisms of Slowed Kidney Fibrosis via Calorie Restriction

The objective of CRM research is to identify compounds that mimic the effects of CR by targeting metabolic and stress response pathways affected by CR without actually restricting caloric intake. With respect to how short-term CR and CRM treatment might directly impact cellular senescence and EMT, one interesting candidate is the AMPK-mTOR signaling pathway. In the in vivo experiments, we demonstrated that AMPK/mTOR signaling in kidney was downregulated with age, and that this was reversed by short-term CR and CRM treatment. In order to further verify this pathway, we induced EMT and cellular senescence of proximal tubular cells (PTCs) in vitro with high glucose. We found that exposure of PTCs to high glucose for 48 hours resulted in the high glucose-induced EMT and cellular senescence, decreased expression of activated AMPK and decreased AMPK/mTOR signaling. Costimulation of PTCs with high glucose and a CRM, both of which activate AMPK, alleviated high glucose-induced EMT and cellular senescence, and increased AMPK/mTOR signaling. Moreover, mTOR was upregulated, and EMT and senescence were increased in AMPK-silenced cells, but were not alleviated in AMPK-silenced cells that had been treated with a CRM. These results indicated that the CRM inhibited EMT and senescence of PTC via AMPK/mTOR signaling. It is possible that the data presented here could be extrapolated to explain the mechanisms of fibrosis seen in other organs during aging, and to provide strategies to ove...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs