Advanced glycation end products or AGEs?

#22

GLP1 agonists reduce AGE damage

  • Study focuses on liraglutide, an old GLP1RA. Newer ones may work better with fewer side effects.

  • They mitigate AGE damage via RAGE suppression, not just by lowering sugar.

  • The study focuses on kidneys, this does not preclude other organ systems being protected by GLP1RAs

"Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease.

Mice with deletion of the GLP-1 receptor displayed an abnormal kidney phenotype that was accelerated by diabetes and improved with co-deletion of RAGE in vivo. Activation of the GLP-1 receptor pathway with liraglutide, an anti-diabetic treatment, downregulated kidney RAGE, reduced the expansion of bone marrow myeloid progenitors, promoted M2-like macrophage polarization and lessened markers of kidney damage in diabetic mice.

Single cell transcriptomics revealed that liraglutide induced distinct transcriptional changes in kidney endothelial, proximal tubular, podocyte and macrophage cells, which were dominated by pathways involved in nutrient transport and utilization, redox sensing and the resolution of inflammation.

The kidney-protective action of liraglutide was corroborated in a non-diabetic model of chronic kidney disease, the subtotal nephrectomised rat.

Thus, our findings identify a novel glucose-independent kidney-protective action of GLP-1-based therapies in diabetic kidney disease and provide a valuable resource for exploring the cell-specific kidney transcriptional response ensuing from pharmacological GLP-1R agonism."

Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation - PubMed

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#23

Kavalactones as inhibitors of advanced glycation endproducts (AGEs) formation

"The end-products of a complex series of non-enzymatic reactions involving glycation of proteins are the AGEs. Elevated levels of AGEs are associated with diabetic complications (nephropathy, retinopathy, cataract), atherosclerosis, neurological disorders and the normal ageing process.

In this study DL-kawain (1), methysticin (2) and dihydromethysticin (3), all belonging to the group of kavalactones, were identified as AGEs inhibitors. With IC50 values of 0.87 ± 0.02 mM and 0.90 ± 0.03 mM for 1 and 2, respectively, the compounds inhibited the in vitro protein glycation significantly better than aminoguanidine (IC50= 4.62 ± 0.23 mM; p= 0.01). Compound 3 showed lower inhibitory activities (IC50= 11.28 ± 0.87 mM). Furthermore, compounds 1 and 2 inhibited the formation of fructosamine, which is an intermediate in the process of AGEs formation. Moreover, 1 and aminoguanidine prevented AGEs formation by chelating Cu2+ and Fe3+. However, these compounds showed less entrapment of the reactive carbonyl species (RCS), glyoxal and methylglyoxal, compared to aminoguanidine. These data indicate that kavalactones prevent early and advanced glycation, partly through metal chelation, and partly through the entrapment of RCS."

I tried kava kava recently and it felt good and improved my sleep dramatically so I did a bit of research into it for lifespan effects. Some promising results for prevention of AGEs. It is also potentially liver toxic with chronic use, but also potentially anti-cancer.