Comparing anti-aging hallmark activities of Metformin and Nano-PSO in a mouse model of genetic Creutzfeldt-Jakob Disease

Neurobiol Aging. 2022 Feb;110:77-87. doi: 10.1016/j.neurobiolaging.2021.11.001. Epub 2021 Nov 11.

Abstract

Advanced age is the main risk factor for the manifestation of late onset neurodegenerative diseases. Metformin, an anti-diabetic drug, was shown to extend longevity, and to ameliorate the activity of recognized aging hallmarks. Here, we compared the clinical, pathologic and biochemical effects of Metformin to those of Nano-PSO (Granagard), a brain targeted anti-oxidant shown by us to delay disease advance in transgenic mice mimicking for genetic Creutzfeldt Jacob disease (CJD) linked to the E200KPrP mutation. We demonstrate that both Metformin and Nano-PSO reduced aging hallmarks activities such as activated AMPK, the main energy sensor of cells as well as Nrf2 and COX IV1, regulators of oxidation, and mitochondrial activity. Both compounds reduced inflammation and increased stem cells production, however did not decrease PrP accumulation. As opposed to Nano-PSO, Metformin neither delayed clinical disease advance in these mice nor reduced the accumulation of sulfated glycosaminoglycans, a pathologic feature of prion disease. We conclude that elevation of anti-aging markers may not be sufficient to delay the fatal advance of genetic CJD.

Keywords: AMPK; Aging; Genetic CJD; Granagard; Metformin; Nano-PSO; Neurodegeneration; Prion.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Antioxidants
  • Creutzfeldt-Jakob Syndrome / genetics*
  • Creutzfeldt-Jakob Syndrome / prevention & control*
  • Disease Models, Animal
  • Electron Transport Complex IV / metabolism
  • Metformin / pharmacology*
  • Metformin / therapeutic use*
  • Mice
  • Mice, Transgenic
  • Mutation
  • NF-E2-Related Factor 2 / metabolism
  • Plant Oils / pharmacology*
  • Plant Oils / therapeutic use*
  • PrPSc Proteins / genetics
  • PrPSc Proteins / metabolism

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • Nano-PSO
  • Nfe2l2 protein, mouse
  • Plant Oils
  • PrPSc Proteins
  • Metformin
  • Cox4i1 protein, mouse
  • Electron Transport Complex IV
  • Adenylate Kinase