Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome
Mitochondrial diseases represent a spectrum of disorders caused by impaired mitochondrial function, ranging in severity from mortality during infancy to progressive adult-onset disease. Mitochondrial dysfunction is also recognized as a molecular hallmark of the biological ageing process. Rapamycin, a drug that increases lifespan and health during normative ageing, also increases survival and reduces neurological symptoms in a mouse model of the severe mitochondrial disease Leigh syndrome. The Ndufs4 knockout (Ndufs4 ā*/ā) mouse lacks the complex I subunit NDUFS4 and shows rapid onset and progression of neurodegeneration mimicking patients with Leigh syndrome. Here we show that another drug that extends lifespan and delays normative ageing in mice, acarbose, also suppresses symptoms of disease and improves survival of Ndufs4 ā/ā mice. Unlike rapamycin, acarbose rescues disease phenotypes independently of inhibition of the mechanistic target of rapamycin. Furthermore, rapamycin and acarbose have additive effects in delaying neurological symptoms and increasing maximum lifespan in Ndufs4 ā/ā mice. We find that acarbose remodels the intestinal microbiome and alters the production of short-chain fatty acids. Supplementation with tributyrin, a source of butyric acid, recapitulates some effects of acarbose on lifespan and disease progression, while depletion of the endogenous microbiome in Ndufs4 ā/*ā mice appears to fully recapitulate the effects of acarbose on healthspan and lifespan in these animals. To our knowledge, this study provides the first evidence that alteration of the gut microbiome plays a significant role in severe mitochondrial disease and provides further support for the model that biological ageing and severe mitochondrial disorders share underlying common mechanisms.
We know that mitochondrial ROS production increases with age because of a decline in mitochondrial function, the activity of several ROS-scavenging enzymes declines with age, and mutations of mitochondrial DNA (mtDNA) accumulate during aging. The question is how to keep our mitochondria as healthy as possible. Personally, I think of Zon2 exercise, taurine, astaxanthin when it comes to keeping the mitochondria healthy. I also think of the once-hyped MitoQ and Q10, which, as far as I know, have not shown results when it comes to slowing down the process of aging (but they might have other specific uses). Now we have acarbose, which might also attenuate dysfunctions in the mitochondria. Exciting times for sure.
I have gone full focus (my new craze) on mitochondrial health. To this end Iāve started taking both Mitopure (Uralithin-A) and Mitoburn (L-BAIBA). Iām also going to start subcutaneous Humanin and MOT-C. Iām already taking Rapa + Arcabose so this study is very exciting Thanks for sharing @RapAdmin
Iām not familiar with Humanin, what is the key research that convinced you this was something valuable to try? The research linked to in Wikipedia (on cultured cells) seems pretty early.
Experiments using cultured cells have demonstrated that humanin has both neuroprotective as well as cytoprotective effects and experiments in rodents have found that it has protective effects in Alzheimerās disease models, Huntingtonās disease models and stroke models.[16]
Humanin is proposed to have myriad neuroprotective and cytoprotective effects. Both studies in cells and rodents have both found that administration of humanin or humanin derivatives increases survival and/or physiological parameters in Alzheimerās disease models.[17][18] In addition to Alzheimerās disease, humanin has other neuroprotective effects against models of Huntingtonās disease, prion disease, and stroke.[19][20][21] Beyond the possible neuroprotective effects, humanin protects against oxidative stress, atherosclerotic plaque formation, and heart attack.[22][23][24][25] Metabolic effects have also been demonstrated and humanin helps improve survival of pancreatic beta-cells, which may help with type 1 diabetes,[26] and increases insulin sensitivity, which may help with type 2 diabetes.[27] In rats, the humanin analog appears to normalize glucose levels and reduce diabetes symptoms.[28]
Rattin shows the same ability as humanin to defend neurons from the toxicity of beta-amyloid, the cause of degeneration in Alzheimerās disease.[8]
Small humanin-like peptides are a group of peptides found in the mitochondrial 16S rRNA, and also possess retrograde signaling functions.
Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects.
Thanks for sharing 