Autophagy Mitophagy controls autoimmune disease

Here below explained is that toxic mitochondria signals the sterile inflammation characteristic of autoimmune disease and aging.

Autophagy (cell recycling) and Mitophagy (mitochondrial recycling or replacement) reduce the inflamasome initiator, NLRP3 the innate cell immune system, activation by their triggers.

It is a reasonable assumption that factors that increase those recycling processes reduce the degree of autoimmune disease.

12 hours of daily fasting. Autophagy.
24 hours of weekly fasting. Mitophagy.
Melatonin 3-6 mgs at night. Autophagy and antioxidant.
DHA 1000 mgs daily. Inhibits Il B a component of activated inflamasome.
Ursolic acid 200 mgs 1-3 times daily promotes metabolism of toxic LPS and promotes fatty acid metabolism and production of beta hydroxybutyrate which promotes the transcription of 44 starvation gene set proteins that repair the cell.
Ubiquinol 100 mgs.  Improves mitochondria.
PQQ 20mgs.  Promotes mitochondrial biogenesis and lowers ROS production, a toxic side effect of mitochondrial oxidative phosphorylation.

The key idea above is that beta hydroxybutyrate,a ketone, promotes repair inclusive of autophagy Mitophagy and their gene initiators expression.
This improves age related inflamaging and autoimmune diseases like PSS, RA etc.

This is the same set of therapeutic interventions that Dr. Dale Bredson used to reverse dementia in 9 of 10 apoE positive patients with cognitive decline!

http://www.clinexprheumatol.org/article.asp?a=10865

Healthy Cells Use Better Pathways For Flow Mediated Dilation

Flow mediated dilation with NO generated by angiotensin and telomerase is healthy because it does not signal or activate the inflamasome.

The metabolic unhealthy cell lacks beta hydroxybutyrate transcription of the starvation gene set which includes telomerase and accordingly alternatively activates the H2O2 pathway which activates the inflamasome and leads to atherosclerosis, fibrosis and apoptosis.

MET epithelial mesenchymal transition is important in cancer metastasis, Barretts esophagus and endothelial dysfunction or atherosclerosis. 

The lack of NO/telomerase, angiotensin 1-7 pathway is the probable cause of diabetes related ED, renal failure, retinopathy, neuropathy and microvascular complications

Below are 2 models of liver fibrosis worsened by inflamasome activation by the hydrogen peroxide pathway and alleviated by NO/telomerase, angiotensin 1-7 pathway. One simultaneously promotes both flow mediated dilation and activates inflamasome induced fibrosis.  

If the small scale cellular injury is ischemia reperfusion injury and the proper response is increased flow through flow mediated dilation then the most resourceful pathway in a healthy cell is NO/telomerase, angiotensin 1-7 pathway that is supported by beta hydroxybutyrate generated starvation set gene expression.  In unhealthy inflamed or age inflamaged cells the less resourceful H2O2-activated pathway is the default which leads to fibrosis.

http://www.sciencedirect.com/science/article/pii/S0891584916303343

Angiotensin(1–7) attenuated Angiotensin II-induced hepatocyte EMT by inhibiting NOX-derived H2O2-activated NLRP3 inflammasome/IL-1β/Smad circuit

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  Ang II activates NLRP3 inflammasome mediated by NOX-derived H2O2 in hepatocytes.
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  Ang II initiates hepatocyte EMT by activating the NOX-derived H2O2-mediated NLRP3 inflammasome/IL-1β/Smad circuit.
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  Ang-(1–7) attenuates Ang II-induced hepatocyte EMT by inhibiting NLRP3 inflammasome activation.

Epithelial-mesenchymal transition (EMT) is correlated with NAPDH oxidase (NOX)-derived reactive oxygen species (ROS). The ROS-induced NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome is a novel mechanism of EMT. Angiotensin II (AngII) induces EMT by regulating intracellular ROS. Nevertheless, it has not been reported whether AngII could induce hepatocyte EMT. Angiotensin-(1–7) [Ang-(1–7)] can inhibit the effects of AngII via a counter-regulatory mechanism. However, whether Ang-(1–7) attenuated the effects of AngII on hepatocyte EMT remains unclear. The aim of this study was to determine whether Ang-(1–7) attenuated AngII-induced hepatocyte EMT by inhibiting the NOX-derived ROS-mediated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, two animal models were established. In the first model, rats were infused AngII. In the second model, Ang-(1–7) was constantly infused into double bile duct ligated (BDL) rats. In vitro, hepatocytes were pretreated with antioxidant, NLRP3 siRNA, NOX4 siRNA, or Ang-(1–7) before exposure to AngII. In vitro, AngII induced hepatocyte EMT, which was inhibited by N-acetylcysteine (NAC), diphenylene iodonium (DPI), and NOX4 siRNA. NLRP3 inflammasome, which was activated by hydrogen peroxide (H₂O₂), mediated AngII-induced hepatocyte EMT. Ang-(1–7) suppressed AngII-induced EMT by inhibiting the NOX-derived H₂O₂-activated NLRP3 inflammasome/IL-1ß/Smad circuit. In vivo, infusion of AngII induced activation of H₂O₂-correlated NLRP3 inflammasome in rat livers and accumulation of α-collagen I (Col1A1) in hepatocytes. Infusion of Ang-(1–7) alleviated BDL-induced liver fibrosis and inhibited the expression of Col1A1 and the activation of NLRP3 inflammasome in hepatocytes. Ang-(1–7) attenuated AngII-induced hepatocyte EMT by inhibiting the NOX-derived H₂O₂-activated NLRP3 inflammasome/IL-1ß/Smad circuit.