#1

I propose that today there are 4 effective, safe and widely available interventions for improved lifespan that everyone should consider: rapamycin, acarbose, glycine and taurine. And an honorable mention to NAC, though the safety is not as clear.

  • Rapamycin

    • Background
      • Inhibits MTOR, and specifically MTORc1, a growth pathway. The most significant effect across animal models, with good safety data in humans. Thought to reduce aging by reducing growth - continuing growth post-adulthood could be a driver of aging.
    • Evidence
    • Safety
      • Used and researched in human transplant patients at 2-5 mg daily dose. Used widely at 4+ mg weekly dose for anti-aging.
      • Most significant potential side effects are related to having kids.
      • Can increase insulin resistance, raising blood glucose. This is likely why it synergizes with acarbose, which lowers blood glucose.
      • Can lower immune system response to bacteria. This can be an issue at high doses used in transplant patients but not reported in lower weekly antiaging usage. Recommend stopping usage while feeling sick.

  • Acarbose

  • Glycine

  • Taurine

    • Background
      • Semi-essential amino acid, produced by the body and also found in food. Thought to extend lifespan by correcting for defeciency that occurs with age in humans and other animals. Vegans notably have lower levels of this since it is found mostly in animal foods, so vegans may have an extra benefit from supplementation of it. Neutral taste.
    • Evidence
      • Main study. References:
        • Mice lifespan extension: median 10%. Equivalent human dose of 2.8-5.7g.
        • Lifespan extension in mice and worms
        • Improved health markers in monkeys (lifespan data pending as the monkeys have not yet died)
        • Blood concentration of taurine declines with age in mice, monkeys, and humans.
      • Non-vegetarians typically eat 40 – 70 mg of taurine per day (Rana, 1986). Vegan diet has reduced amounts of taurine, with seaweed and soybeans as plant based sources. Vegans have been shown to have lower but normal blood levels of taurine (Laidlaw, 1988).
    • Safety
      • Found in diet and is an amino acid, so should be safe.
      • Improved health markers and lifespan in model animals as mentioned above

An honorable mention goes to N-Acetyl-Cysteine (NAC). When combined with glycine there is significant lifespan extension. However, it has not been reproduced and in one study it increased lung cancer in mice. I think it is worth taking, but the evidence is not as clear cut as the previous supplements.

What do you think?

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#2

I think quite a few could qualify as safe, effective, and widely available but don’t see anything wrong with your list.

Glycine I always feel is not essential as it can be obtained in effective quantities through diet. I don’t personally consider supplementing it.

Statins although controversial could be added to your list. Since coronary artery disease kills more people than anything else preventing it will extend average lifespan. Of course if your LDL is below 60 or so you don’t need them for lipid lowering.

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#3

Given our poor mechanistic understanding of aging and trouble interpreting even wide scale human data (see: metformin), I am skeptical of effectiveness of interventions that have not not produced significant effect in reproduced animal models.

#5

Really nicely done writeup and agree with the approach.

Other things on the radar might be 3 days of dasatinib and quercertin due to potent senolytic effects. It is however unclear how often one might choose to take this regimen.

With the NAC, it would seem reasonable to utilize a version that is absorbed well and crosses blood brain barrier. I know there is some debate in this space, but for the time being, I advise my patients to take the NAC ethyl ester (NACET) version as it would seem to have better evidence both in regard to limited dose (as better absorbed) and getting glutathione optimization in the central nervous system.

An interesting article on the NACET is here: Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage - PMC

Interested in other’s opinions on this.

One of the big issues with the range of possible is choosing what one actually does. There are real risks with each additional supplement/medication that there might be interactions/cancellation of other good effects. Making sure there is a clear reason and low risk of side effect/interaction for everything you put in your body seems a good policy!

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#6

Thinking about statins, there is a risk to using only animal models - nonhuman animals basically don’t die of heart disease to my understanding, while it is the top cause of human death. So animal testing will not really reveal things that increase or decrease your odds of dying early to vascular disease, which is a significant limitation.

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#7

But presumably things which reduce the rate of multiple aging-related diseases for that specific animal, will reduce multiple aging related diseases (incl heart disease) in humans, if the mechanism is conserved.

#8

I’m not trying to argue with you over your Statin comment. I’ve heard before that they are great for longevity. I’ve also seen this and not bothered to look up all the references:

I think their biggest complaints have been long known. CoQ10, vitamin K, mitochondrial toxin, they didn’t even mention T2D. Stories are out there, with the propaganda levels today the truth is very hard to find.

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#9

I don’t take statins personally but have been convinced by the many meta-analyses published in the last 10 years, this one being one of the most recent with over 4 million patient-years of follow-up:

Regarding the article you linked I don’t know what Tyler Durden’s qualifications are but the sources he cites are either weakly powered with fewer than 100 participants or expert reviews. His main concerns seem to be theoretical mechanistic ones regarding CoQ10 and K2 synthesis. That being said you could supplement either of those if you were concerned. I am more convinced by outcome data from longterm studies on tens of thousands of people.

One quite alarming claim in the article is that statins are drivers of heart disease which I don’t think is supported by the literature.

To be clear there is a small risk of side effects from statins and they are not for everyone but I do think they are a powerful and well tolerated drug for healthy aging.

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#10

I personally take Statins as do every member of my family in my age-group or older.

There are risk/benefit issues to consider with any intervention, including statins. However, the risks have been overstated, and the benefits downplayed by many. The misinformation cycle has to be so confusing for healthcare consumers!

I personally cannot get my ApoB down to the 50-60’s, which is where I want it to be, without a statin. This is despite being fully plant-based. I can get it into the mid 80’s through lifestyle alone.

There is solid evidence that multiple issues relate to vascular disease, including glycation of blood vessels, inflammation, blood pressure, lipids and exposure to toxic substances (e.g. tobacco as an example).

Statins do a great job of stabilizing/reversing plaques, along with optimal management of all the other items listed above (and more).

If you can get your ApoB into an ideal range without them - that is amazing and great. If however your choice is running an ApoB that is elevated vs. taking a statin, I’d be very cautious in dismissing the value and importance of ideal lipid management. It is the number one killer and worse yet - disabler, of humans in western societies.

There are too many people not monitoring and managing these issues. In my work as an ER Physician (now for 25+ years), I see a lot of people who think their vascular health is fine, presenting with significant vascular disease and having poor outcomes that once they occur are not reversible.

Obviously, the ideal situation is to have amazing genetics and not need drugs to obtain these values I’d consider optimal.

Please note that this is general information and not to be used for any specific patient and is not meant as medical advice for any individual.

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#11

Statins may be great for most, but I believe a significant minority get significant side effects. I enjoyed the lowered apoB, but after some months got severe muscle pain from mitochondrial damage.

After stopping the statin, the pain took months to disappear. Depletion of CoQ10 seems to be a real effect and I don’t know if supplementation would have prevented the pain.

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#12

Statins are the only proven longevity drug in humans.
They are the best if tolerated with no side effects.

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#13
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#14

Notably simvastatin failed ITP: MPD: ITP survival analysis:   simvastatin

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#15

If you look at the first line of the article you will see that it is just a reprint of the article from the epoch times. I do not believe anything I read, but keep reading things anyway just for the practice.

The Media Bias and fact checkers lie as much as the rest.

Also I think statins have an even chance of making your life longer. I think the odds are worse than even that they make it better. I know too many that suffered and quit. Also I think LDL is part of the immune system. It detoxifies the LPS and hauls it away. The best solution today is Cavadex. It sucks but I’ll know within a week whether it lives up to the hype.

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#16

Nothing has changed.

Today it is Edward Bernays on steroids.

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#17

Epoch Times is even worse.
https://mediabiasfactcheck.com/?s=Epoch+times

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#18

I get it. But there’s bias and there’s fecal.

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#19

A really good evidence based primer on this topic, for those who want to learn more about the number one killer/disabler - irrespective of one’s position on statins, the bottom line is a high ApoB has an extraordinary predictable bad outcome.
This series is remarkably good, can be a bit of a struggle for folks who haven’t done a science doctorate - but is still digestible. Lipid Series - The Proof
Listening to scientists and physicians who have lots of experience, and have no product to sell you, and truly just strive to give their best version of the science is valuable. I found this series to reinforce everything I know as a physician with 4 board certifications who doesn’t make a penny from someone taking statins - actually I make a lot more if they don’t as we’ll need more emergency physicians to care for all the vascular disasters!

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#20

@Bicep The video Rhonda Patrick produced of her interview with Ron Krause (I posted here some time ago) discussed how ldl picks up the LPS which is then cleared from the body when the ldl is picked up by the liver. Statins make the liver produce more ldl receptors to remove ldl from the bloodstream. This is why ldl measurements decrease and how the lps gets taken out. So, statins help with removal of lps, according to Krause.

I think this is the one. Check it out.

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Parkinson's disease
#21

My bempedoic acid arrived today, so I will begin that and hopefully have the new numbers around June. I could not take statins because it caused severe muscle soreness even with CoQ10 supplementation and taking the lowest dose every other day. Everyone has a unique biology. I hope bempedoic acid will work for me.

If not, I’ll have a 6 month supply up for sale. :wink:

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