I think you can illustrate the different expression like this
| Person | Age of death | ||||
| 1 | 20 | ||||
| 2 | 46 | ||||
| 3 | 52 | ||||
| 4 | 58 | ||||
| 5 | 60 | = Median lifespan | |||
| 6 | 72 | ||||
| 7 | 84 | ||||
| 8 | 90 | ||||
| 9 | 102 | = Maximum lifespan | |||
| 10 | 112 |
Life expectancy = (Sum of all ages) / (Total persons) = 695 / 10 = 69,5 years
So median lifespan is almost the same as life expectancy. So if life expectancy goes up with 5 years then the result is 69.5 + 5 = 74.5 years.
I nominate “carb control” as one of the four. If there are only going to be four I would lump acarbose, canagliflozin and empagliflozin, etc. into one category.
I like the the category “carb control” or what do you say about “carbohydrate restriction” instead? But on the other hand it would be great to specify what type of carb control has the best effect. For example lifespan data differs quite much between Acarbose and Metformin. The ITP showed recently that Acarbose had the best effect but I don’t know how other studies are in the field and in other species. Someone?
Exercise, diet, sleep, Rapa.
@KarlT Do you have median and maximum lifespan data on mice on the first three ones?
For example regarding exercise I wrote two posts above here. What do you think about that? Exercise can not be the best one.
This is the latest version of the summary. I’m trying out and see if Acarbose fits in there but it’s a compound that I don’t have so much knowledge about more than the ITP. For example what is the safety of it, do you need prescription, what is the cost, does it extend lifespan if it started early and/or late in life? Any suggestions?
No. And I realize your question was about longevity. But I think my four choices are best for health span. The problem with individual interventions is that we don’t know the effects of combining these interventions.
There have been 1604 clinical trials on Rapamycin? Wasn’t it just 64? Seems to be a large discrepancy.
Also cost and safety for Rapamycin are a bit low? Three plusses maybe?
There are some interesting indication where combination of interventions are done and more of that will come in future.
Here is for example a combination with rapamycin and acarbose in the ITP which lead to the biggest increase male lifespan which they have reported.
Here is interesting additative effects when rapamycin is combined with calorie restriction.
Here is one study on the additative effect on rapa and CR on fruit flies:
Even if these are interesting indications of promising combinations between interventions we are long from getting everything optimal. I really like this image that I created awhile ago to point out that it’s all about finding the right balance between anabolism and catabolism.
Possibly acarbose should be separated from SGLT2 inhibitors and both items listed. They act upon the body in very different ways and I think (please any forum members correct me if I am wrong) they both have beneficial effects apart from carbohydrate restriction effects.
The 1604 clinical trials on rapamycin and on the other interventions is from this study: The road ahead for health and lifespan interventions - PubMed
Regarding cost of rapamycin I think three plus is too low price. There are many people here trying to lower their cost of rapamycin and some people don’t have the money for buying it. Here in Sweden if I buy it from the pharmacy the cost is 386 USD for 100 mg so my yearly cost will be around 1100 USD depending on dose. It’s quite much money if you compare that to calorie restriction which is free and even saves money. But let’s see what the other two interventions cost. Do you know what the yearly cost of Acarbose is?
FWIW
100mg, 90 tablets cost $14.45 with a discount coupon in North Jersey, USA at a Rite Aid Pharmacy as of 12/11/2022
That is a really great price! Is that common in the USA? Then I understand @DeStrider why you want more plusses on rapamycin. Is it the same price for you?
AKG Alpha Ketoglutaric Acid ?
Matt Kaeberlein had said in a Tim Ferris interview was most promising anti - aging compound to investigate further after rapamycin.
Also see NIH articles
It would knock rapamycin down from number two to number four but I think you should consider adding combinations. Rapa + acarbose, Rapa + Metformin.
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.
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
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!
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.
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.”
