Glucosamine instead of Metformin and Rapamycin?
I happened to read a very old blog by Vince Giuliano regarding Glucosamine
In it he gives sufficient evidence that Glucosamine extends life in nematodes, mice, and humans, by activating AMPK, and modulating mTor.
There is one caveat: The life extension benefits are lost if antioxidants are also supplemented at the same time.
There are two questions that come to mind:
a) If this supplement is readily available, cheap, and gives the same benefits as Rapamycin and Metformin combined, without the side-effects, and since this information is available for a long time, why all the fuss about Metformin and Rapamycin? Why bother? It seems to me like a no-brainer. Am I missing something?
b) I currently supplement with antioxidants NAC and Glutathione. How can I continue to take them and still reap the benefits of Glucosamine? I would assume some intermittent schedule. But no sure about the intervas.
Any ideas will be greatly appreciated.
I don’t think your #1 holds true. Efficacy of rapamycin for life extension is much higher and per dr Kaeberlein in reasonable doses rapamycin is no more dangerous than aspirin. Also per the research paper you have attached the average lifespan extension in mice is just 6%; basically, no better than Metformin or berberine. This is quite lower than rapamycin or calorie restriction in mice, which can achieve ~25% independently. Now human lifespan is much less pliable than mice, which means that 6% in mice may not extended human lifespan at all. Hence serious longevity researchers like Walter Longo don’t bother with such dubious therapies like Metformin and that’s why Glucosamine is not so exciting either. Now acarbose is much more interesting than Metformin and berberine or glucosamine as it extends an average lifespan in mice by 22%. Hence my suggestion would be to seriously consider acarbose , rapamycin and calorie restriction. These are heavy hitters and are very widely studied. Also I think your glutathione is actually a good and safe supplement although it doesn’t extend the lifespan.
The issue with Berberine is that it is just not as widely studied as Metformin and not fda controlled. It is probably ok and little bit beneficial for ldl-c and high blood sugar. If you take it do it just once a day 500 mg and cycle it on and off - 6 weeks on and 2 weeks off. With respect of nac and rapamycin I am not aware of any study investigating interactions between the two. That said nac being amino acid and rapamycin acting on mTOR, I suspect that they would counteract each other. I don’t see how staggering the treatments between the two be of any value. Now I think it makes for interesting lab experiment on mice but I wouldn’t try it on yourself. Idea is to minimize number of treatments and interactions as there are just too many unknowns.
With respect of rapamycin, I’m curious at what dosages the skin infections are observed? Can you find out from the doc who prescribed it to you?
Anyway the idea behind combing cr and rapamycin and acarbose is that you can achieve combined effect without having to resort to extreme intervention. That is e.g. instead of doing 40% cr restriction you do 15% and instead of taking 10 mg rapamycin you take 3 mg and you still a have the same benefit without incurring a high risk like skin infections (and yes you should be concerned about it as you don’t live in sterile lab) which comes with more extreme interventions.
I write this post because I have read that AMPK activation could possibly be detrimental in neurological some diseases. (not knowing if it is correlation or a possible causation).
I am not bashing AMPK activation. Its has many benefits but it might be the right time for me to dig in deeper and be more specific in my AMPK activation. I consider the possibility that I AMPK can be overactivated.
One paper stated that “results demonstrate that AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis.”.
“AMPK is a master energy sensor which was reported to be overactivated in the brain of patients affected by these neurodegenerative disorders. While the exact role played by AMPK in these diseases remains to be clearly established, several studies reported the implication of AMPK in various signaling pathways that are involved in these diseases’ progression.”
“Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation. AMPK is a master energy sensor which was reported to be overactivated in the brain of patients affected by these neurodegenerative disorders.”
this leads me to the question: which are the best ways to activate AMPK in muscles, fat and liver etc without over activating it in hypothalamus. And maybe even in some situations the aim might be to inhibit hypothalamic AMPK in the brain .
Some indications point towards Lipoic acid and quercetin as supplements that inhibit hypothalamic AMPK while activate AMPK in muscles, liver and fat cells.
Green tea and Curcumin promote neurogenesis in hypothalamus. While activating AMPK outside the brain.
I have not seen any research about metformin and the effect it might have on disorders in the brain. I find exercise and diet to be the safest ways to activate AMPK. But I look for the smartest combinations of drugs or supplements to activate AMPK in some cells in my body and possibly to inhibit it in the brain, or at least avoid over activating it in my brain. I post these thoughts here and hope that some might reflect on these ideas and lead me on to a better understanding of AMPK activation.