The four best longevity interventions?

It would knock rapamycin down from number two to number four but I think you should consider adding combinations. Rapa + acarbose, Rapa + Metformin.

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I purchase mine from India and use GFJ, so my cost is about 3 USD per week. That would be 156 USD per year. Even less if I take a month washout period every so often. So costs vary wildly between locations.

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Things are really coming together on this image. I like the direction you’re going with it.

It seems like Canagliflozin is likely the 4th compound (or 17 Alpha estradiol, but its very hard to get).

For more info on Canagliflozin and Acarbose see our pages on each:

Acarbose: Acarbose - Details On Another Top Anti-Aging Drug

Canagliflozin: Canagliflozin - Another Top Anti-aging Drug

17-Alpha Estradiol: 17-Alpha Estradiol - Another Top Anti-Aging Drug

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I am very interested in 17A-Estradiol. It works on a different pathway than Rapamycin, correct? I am hoping for a larger add-on effect. Any idea when it may be commercially available?

NOTE: NDGA is toxic to humans. DO NOT TAKE NDGA!

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Yes - it should be mostly a new pathway, though it seems there is likely some overlap - see this: Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation | Immunity & Ageing | Full Text

I also am hoping for a larger add-on effect. We are perhaps 3 to 5 years away from it becoming commercially available as a unique drug; the only company I’ve heard of that is doing anything with it is Apollo ventures, and one of our forum members mentioned here that they are still just doing animal trials - so its a long way away from FDA approval.

That said, its just the other version of Estradiol that is already used by millions of women (beta-estradiol), and my understanding that given that in any manufacturing process of estradiol there will likely be both versions of this chiral molecule included in the ultimate product, so women are already taking it in their regular hormone treatment. Of course, the “alpha” version of the molecule hasn’t been trialed in men yet, so formal clinical trials still need to be done.

Yes - I looked at NDGA. It looked interesting, but it was pulled from the market many years ago due to human toxicity issues.

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Sleep is obviously important to staying healthy, just like breathing is. But I don’t think I’ve ever seen a scientific study that shows that that you can increase longevity with sleep.

Good sleep keeps you alive longer because you’ll die without it, just like you’d have a miserable, short life if you didn’t eat and breath properly. But you’re not going to add years to your life through sleep.

I feel like a few people in this forum are confusing “you’d be unhealthy without this” and “you’ll increase your natural lifespan with this.”

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If you don’t think sleep adds to health span and lifespan then you need to do more research.

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Acerbose would be a good candidate for the list.

I have heard of Alpha-ketoglutarate in different podcast but I have seen lifespan data on it yet. Thanks for the studies. My guess is that this compound is not in a place to be classied as the best intervention we have. But it would probably be a compound to have in another list. Let’s call that list for example “Upcoming longevity future compounds to keep an extra eye on” :+1:

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Very interesting point! But the science that a combination strategy I would say is not that strong yet. More studies needs to be done on this before it can be qualified to be best intervention. Now it’s only ITP which has shown this which is great but it would be even better to see it replicated in different species. Safety profile etc. There is lots of unknown factors here. But very promising combo!

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Ah, great helpful diagram! Peter Attia did suggested that Canogliflozin would be probably better at place third instead of Acarbose. What do you think about that?

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Yes, 17A-estradiol is a interesting one! Curious, what pathways are we taking about when it comes to 17A-estradiol which differs from rapamycin? Because biological processes have a tendency to go into each other.

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Interesting response from Peter. Lifespan increase larger in acarbose but yes more good additional health data on canagliflozin. I defer to Peter on all things medical.

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I am not an expert on 17A, but it doesn’t affect mtor the same as rapamycin, correct?

It appears 17A estradiol is available commercially now under the name Alfatradiol. Brand names Avicis, Avixis, etc… See article below.

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Very good that you lift this because it’s little bit tricky one this. As you say we need to breathe also to be able to live or eat calories or that we get nutrients etc. So sleep is some form of natural basic interventions for longevity and the problems occur if we start acting against are nature and get problems in our sleep. CR and Rapamycin are more external interventions which we can add to our life on top of the natural basic interventions. Tricky one this or what do you say?

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I have added it to the third place on the moment to test it out if it fits there or not.

I don’t really think it’s tricky.

If it’s something humans won’t die or become unhealthy without, but that they can use to extend their lifespan, then it belongs on the list. (Rapamycin, calorie restriction, etc.)

If it’s something that humans will die or become unhealthy without, then it should be considered “healthspan” stuff and doesn’t belong on the list. (Sleep, eating, exercise, etc.)

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It’s also pretty intuitive if you think about it . . .

Humans have been around in our current form for tens of thousands of years. If there was something as simple as a certain kind of food or sleep habits that extended our maximum possible lifespan, then we would have figured these things out many thousands of years ago.

The maximum possible lifespan for humans hasn’t increased with better nutrition and healthcare; it’s just the average lifespan that has increased, because more people are getting closer to the maximum possible age before dying.

It was absolutely possible for people to live to be 100 years old in ancient times, as long as they didn’t die from childbirth /disease /wars /famine /etcetera first.

The stuff that belongs on your list are the things that will increase the maximum age that humans will have the opportunity to live to . . . if they stay healthy and don’t get eaten by a bear or something.

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Perhaps 8 hours of sleep is overrated.

Though, rapamycin has increased my sleep time and my sleep quality.

“A new study looking at sleeping patterns in three traditional hunter-gatherer tribes suggests ancient humans were just as sleep-deprived as we are, averaging a little under 6.5 hours of shut-eye every night.” Actually NOVEMBER 02, 2015

“In some ways, the sleep in these traditional human groups is more similar to sleep in industrial societies than has been assumed. They do not sleep more than most individuals in industrial societies”

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This study appears to confirm your point.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694114/

Conclusion

Our results revealed that people who sleep more than 7.5 hours per night have decreased levels of the anti-aging protein klotho in their serum, thus being more at risk of aging-related syndromes.

Sweet spot seems to be 6.5 to 7.

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