• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

NMN extended lifespan of mice with a mitochondria disorder called Leigh syndrome

nmn

  • This topic is locked This topic is locked
1 reply to this topic

#1 Phoebus

  • Guest
  • 851 posts
  • 237
  • Location:Upper Midwest, US

Posted 06 March 2019 - 03:10 PM


 

Article OPEN Published: 

28 February 2019

 

Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease

Scientific Reportsvolume 9, Article number: 3073 (2019

 

Abstract

 

Leigh syndrome is a mitochondrial disease characterized by neurological disorders, metabolic abnormality and premature death. There is no cure for Leigh syndrome; therefore, new therapeutic targets are urgently needed. In Ndufs4-KO mice, a mouse model of Leigh syndrome, we found that Complex I deficiency led to declines in NAD+ levels and NAD+ redox imbalance. We tested the hypothesis that elevation of NAD+ levels would benefit Ndufs4-KO mice. Administration of NAD+precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated lactic acidosis. NMN increased lifespan by normalizing NAD+ redox imbalance and lowering HIF1a accumulation in Ndufs4-KO skeletal muscle without affecting the brain. NMN up-regulated alpha-ketoglutarate (KG) levels in Ndufs4-KO muscle, a metabolite essential for HIF1a degradation. To test whether supplementation of KG can treat Ndufs4-KO mice, a cell-permeable KG, dimethyl ketoglutarate (DMKG) was administered. DMKG extended lifespan of Ndufs4-KO mice and delayed onset of neurological phenotype. This study identified therapeutic mechanisms that can be targeted pharmacologically to treat Leigh syndrome.

https://www.nature.c...598-019-39419-4


Pretty obvious they are gearing up to try this therapy with humans who have various mito disorders. Wonder how long before human trials? 


Edited by Phoebus, 06 March 2019 - 03:09 PM.

  • Informative x 1

#2 Phoebus

  • Topic Starter
  • Guest
  • 851 posts
  • 237
  • Location:Upper Midwest, US

Posted 06 March 2019 - 03:26 PM

 

 

Therapeutic benefits of NMN were mediated by elevation of alpha-ketoglutarate (KG) levels and suppression of hypoxic signaling.

 

So thats the mechanism they seem to be focusing on here. 

 

 







Also tagged with one or more of these keywords: nmn

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users