Great. Looking forward to seeing how it gets on. If it’s successful I’d like to see it tested with rapa too. It’s possible they can both extend life individually but cancel each other out together.
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Great indeed. Also, the Baylor team must be confident in their findings to push it to the ITP. Otherwise, it would be a total disgrace for them if it fails. It can still fail, of course, but I assume that at least they’re honest in their research. On the other hand, this reminds me of selegiline/deprenyl. I contacted the lead investigator of the recent paper six months ago and again last month, and they never got back to me. My guess: they know that selegiline does not extend lifespan and that previous studies were incorrect. (Or my email went to their spam folder 
)
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I recently listened to a podcast in which a researcher was touting the many benefits of collagen supplementation. But one benefit I hadn’t considered is IF one is eating a heavily animal protein diet (as I am) then having excess glycine is useful to counteract the excess methionine (which is pro aging) and pushes the cycle into glutathione production. I would gather having NAC as well would additionally help here. The suggestion was for roughly 12-15g of glycine daily for meat eaters, of which he thought roughly half could come from collagen supplementation and the rest from glycine supplementation. I haven’t seen research on this, but if excess methionine is the root cause of lower lifespan from higher meat consumption, then this could ameliorate this issue (at least partially). The below article discusses that higher methionine diets show correlation to CVD events. This may also be a reason that glycine supplementation can extend lifespan.
I’m taking 6g of glycine with 100mg NACET and 28g collagen in the morning. Then I eat a heavily animal-protein low-carb diet. Hopefully the glycine is counteracting the methionine.
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It seems your Glycine intake is more than adequate. But 100 mg of NACET is only 1/6 the dose of Cysteine you should be taking if you are over 60.
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Thanks, @DeStrider. I may have been sold snake oil, but I’ve read that 100g of NACET (or “the fart pill” as my wife calls it) is bio equivalent to 20x that in NAC, or 2g of NAC. I assume you’re suggesting it is only 10x equivalent, or 1g, and I should instead be taking 6g NAC? I had considered doubling it but not “sextupling” it Also, I’m not quite 60 (53).
By taking more NAC will I protect better against the methionine impact (which is important if this is the first order impact of eating meat)? I don’t want to over take antioxidants (I take 12g athraxanthin) because I don’t want to dilute my exercise signaling, and want my immune system to be effective (particularly against cancer).
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You can find my thoughts on amino acids like NAC, Glycine and Taurine here:
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Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice - PMC Selenium supplementation, mimics methionine restriction diet
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I hope ITP notices if the glynac effect is just caloric restriction due to NAC tasting nasty 
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That’s very interesting, @Rapamune1 . I’ve always been nervous to overdose on selenium (and burn out my thyroid). We have a lot of Brazil nuts at home and I just read watch nut can have 90mcg of selenium, almost double what the daily recommended amount is. But if I can restrict methionine, this might be a good biohack.
The safe upper limit for selenium is 400 micrograms a day in adults. Anything above that is considered an overdose.
To add to your thought:
https://www.nature.com/articles/srep19213
Abstract
The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73–0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer and prostate cancer, but it was not associated with colorectal cancer, bladder cancer and skin cancer
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These results do not indicate that NAC works against rapamycin. First of all, ashwagandha and glucosamine do not work mainly through mTOR inhibition, so any nullification of their effects by NAC does not necessarily indicate that NAC will prevent mTOR inhibition in response to rapamycin. Secondly, the concentrations of NAC used in these studies are massive. They are far higher than what you would get in the blood from ingesting it.
Thanks for posting. This study is the most interesting one among those you posted, because it has more direct relevance to auophagy. It does indeed suggest that NAC can inhibit autophagy, and therefore might antagonize the effects of rapamycin. However I very much doubt it will do so in humans after ingestion. Look at the concentrations they used. 10 mM or higher concentrations of NAC inhibited autophagy while 1 mM did not significantly inhibit it but only showed a trend towards inhibition. 10 mM is equivalent to 1630 mg/L! That is way above anything you can get in your blood from ingesting NAC. In one study peak NAC concentrations ranged from 0.35-0.4 mg/L in humans after oral ingestion of 200-400 mg of NAC on a fasting stomach. Clinical pharmacokinetics of N-acetylcysteine - PubMed So you’re not going to get anywhere close to the concentrations that inhibited autophagy by ingesting NAC.
Bottom line is. When looking into the effect of something based on in vitro studies, you always have to put things into perspective before jumping to conclusions. One of the most important thing here is to look at the concentrations used in vitro and compare them to concentrations that are achieved in vivo with ingestion of the compound. Only then will you find out if this has any relevance to what might occur in vivo. This must always be done before jumping to conclusions, because more often than not, concentrations used in vitro are far higher than what you would ever get by ingesting the compound.
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If we’re talking life extension, which I was, I believe the gains in animal studies we’ve seen from glucosamine and ashwagangha ingestion very much come from their effects on mTOR. We also have very good observational studies on this in humans.
Re the concentrations/dosages, they of course matter, that goes without saying, but the fact of the matter is when they gave mice glucosamine and NAC at the same time, the beneficial effects of ROS directly derived from mTOR inhibition were abolished. That’s in vivo. That’s also specifically about autophagy and specifically pertains to levels in the blood after ingestion so your reply dimissing it as relevant on both those counts is very confusing. On the balance of evidence it seems a high probability to me that NAC interferes with beneficial effects of mTOR derived autophagy in normal human doses.
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I would also argue that the concentrations merely indicate the degree to which the abolishing effects occur not whether they occur or not.
What life extension are you talkinig about? Ashwagandha has not to my knowledge been found to extend lifespan in rodents. If I’m missing some rodent lifespan study on it please post it. Also I have never seen a study showing that ashwagandha inhibits mTOR. Glucosamine has been found to increase lifespan, but I have seen no good reason to think the lifespan increase is caused by mTOR inhibition. Glucosamine is not an mTOR inhibitor. Sure it’s possible that it might influence mTOR indirectly, but I have seen no evidence of this occurring after ingestion in rodents or humans so what you’re saying is a long stretch.
That’s unsupported speculation. There is no mention of mTOR or autophagy in that mouse study you linked to above (PMID: 24714520). So you’re just wildly speculating based on that nematode study. Please show me rodent or human studies that show that glucosamine inhibits mTOR after ingestion. I don’t think such studies exist. Until I see such studies I’m going to assume that it’s very unlikely that glucosamine inhibits mTOR significantly after ingestion in humans.
That’s often true, but if adding 2000 mg of salt to your diet increases the blood pressure of some people modestly, you don’t go and start telling people to start getting worried about adding 20 mg of extra salt daily to their diet because it might increase their blood pressure. Dose is everything in biology.
Anyways, I’m not interested in debating this more. I think you make too many errors in your judgement and logic here.
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On point one there is an abundance of evidence that both ashwagandha and glucosamine inhibit mTOR via the AMPK pathway. There are also trials that show ashwagandha increased lifespan in mice. Google will be your friend and I assure you the papers aren’t hard to find.
On point 2 they literally explain in the mouse study how glucosamine-induced ROS activity was suppressed by NAC. Just because autophagy wasn’t mentioned doesn’t mean it wasn’t prevalent and wasn’t suppressed. Both those things happened because ROS induces autophagy (via AMPK and other pathways) and NAC scavenges ROS. Read the study in the context of those biological facts. No speculation required.
I too am not interested in further debate or doing your research for you. This is my final contribution on the matter.
In general, making claims that are highly speculative and far fetched and with holes in their logic, requires that you support them, or else you’re not really providing any value with your posts.
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Thank you for bringing this information to our attention.
As someone who knows nothing about either of these and not likely to take them in the near term, it would be helpful in general to paste a few of these supporting studies in your post so people can follow. If it is really very easy to find these sources then it should be very easy to post them for those of is who are not as invested here. If you do, then this forum continues to be a source of great information which is easy to digest. If you don’t, acknowledge that people are less likely to take your arguments as seriously (even if they are correct”) because there are no sources and just sound like an argument rather than a discussion.
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My post included a sum total of four linked studies.
Thank you: very helpful.
It did. But none of them make a good case for your statements that glucosamine or ashwagandha increase autophagy and inhibit mTOR, or that NAC inhibits autophagy, in humans. You can talk all you want about worms and in vitro studies, but in the end you have to put things into context to really see if there are any reasonable chances of this applying to humans ingesting these compounds at normal intakes. After all, we are not worms or cells in cell culture.
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