#49
4 Likes
#50

Sample SapereX report.

saperex report
saperex report714×924 121 KB

As to what any of the above means, I don’t know.

3 Likes
#51

Mice as models. Short video.

1 Like
#52

This is a good podcast with Brian Kennedy, and covers lots of rapamycin questions people commonly have:

LIVE AMA: Longevity Scientists Answer Your Health & Longevity Questions LIVE

5 Likes
#53

This sums up Rapamycin nicely.

2 Likes
#54

Dr. Kaeberlein’s recommended supplements.

4 Likes
Which supplements do you think are still worth taking?
#55

I like Matt K’s rational for supplements… I have taken for years everything he suggests and have good blood measurements – high normal.

2 Likes
#56

Yes. I completely agree with all of his recommendations and take them all myself. I’m glad he considers Rapamycin a supplement.

However, I’m surprised he isn’t doing anything for lipid control and arteriosclerosis prevention. Also he doesn’t mention glucose control either even though the ITP showed strong benefits of Metformin paired with Rapamycin.

Overall his recommendations are solid and hard to dispute. It’s a good foundation for everyone.

4 Likes
#57

A philosophy that’s entirely sensible, but as he says himself, very conservative. Vitamin B12, Omega-3, magnesium, vitamin D. Here’s what’s funny - yes, make up deficiencies, but most of us on this site, I suspect, are not actually deficient in these. Also creatine, protein powder and collagen peptides and rapamycin. I’ve also heard him say that he took a multi-vit pill, don’t know if he still does.

It’s interesting to compare this with the list Nick from the Physionic channel gives as supps that have evidence behind them. Creatine makes it, but also lutein and zeaxanthin, with greater or lesser scientific validation, omega-3, taurine.

Then there’s Brad Stanfield’s list, creatine, protein powder, multi-vit, psyllium husk, omega-3, melatonin, tmg, hyaluronic acid, collagen peptides.

Some supps seem to repeat, like creatine and omega-3 across all three. Or appear on more than one list, like a multi-vit, collagen peptides, protein powder.

Amazingly, from all lists, I don’t take creatine, collagen peptides, multi-vit, hyaluronic acid, melatonin. But I take all the rest!

I guess I am not as conservative, because I take a few more in addition. Some of which I admit have little to almost none evidence behind it, like 3mg/day boron - but those are low cost and importantly low risk.

The other thing is that you have to watch dosing and protocol. I do tend to be conservative with doses, and rather don’t megadose.

3 Likes
#58

You also have to realize that Dr. Kaeberlein and Dr. Stanfield talk with each other as Dr. K is helping Dr. Stanfield with his rapamycin RCT. Nic from Physionic also interviews lots of different doctors and researchers. They share their ideas and the good ones get adopted.

So, yes, everything in the video is what doctors, scientists and specialists in longevity firmly believe are the best supplements to take at a FOUNDATION level. Everyone’s stacks then diverge based on their individual beliefs.

I take all of the supplements you mentioned (except psyllium husk) and more.

Dr. K is also positive on taurine, tadalafil and a few others. Just not in this video.

4 Likes
#59

Matt finishes his supplement list with Rapamycin in the video. (He gives a rationale for why he thinks of it as a supplement vs a drug in his case). It was surprising to me that, as he cycles Rapamycin for 12 weeks, his breaks between dosage can be 6 months to a year. That certainly seems like a long period of time. I am curious what his rationale is for this long break given his experience as a researcher.

2 Likes
#60

From what I’ve heard him say, is that rapamycin effects are surprisingly long lasting. A mouse that has been on rapamycin for a relatively short period of time keeps reaping the benefits for long after cessation of treatment. He therefore feels that there is relatively less upside to longer rapamycin exposures, while long breaks minimize the risk of any unforeseen side effects in humans longer term. So his protocol looks to optimize the risk/reward ratio, and he settled on that. He also freely admits that he is just guessing when it comes to dose and timing protocol, and doesn’t have firm evidence one way or another.

We’re all guessing about the optimal dose and timing of rapamycin.

6 Likes
#61

Kaeberlein’s guesses are better educated than mine. I listen to him.

3 Likes
#62

This is where mechanism helps. If a dose of rapamycin’s main positive mechanism is recycling the x% most inefficient mitochondria in a cell (which the body then replaces with average mitochondria) then the benefits of repeat in a short period of time reduce.

2 Likes
#63

Yes that sounds about right as far as logic goes. IMO however it is premature to take breaks early on. In the rodent studies where they had lasting benefits after stopping rapamycin intake, that was usually after taking it for months, which would be equivalent to years in humans. My guess is humans would need to take it for at least some years before having any lasting effects. Another point to consider is that the mice in the longevity studies take massive doses of rapamycin, much more than us humans are taking. Therefore they have had a lot more extreme exposure before taking a break. That exposure might give them long term effects. Humans in contrast take a lot lower doses and would therefore likely need to take rapamycin for much longer to lock in some benefits. Taking breaks before one has reached a high total cumulative exposure doens’t make sense IMO. Maybe after taking a high dose for several years one will start locking in some benefits. It’s hard to say.

7 Likes
#64

If you consider mechanisms, however, the conclusion depends on the mechanism.

My preferred mechanistic hypothesis is that each dose of rapamycin causes the destruction of a proportion of mitochondria (mitophagy). Each cell selects the mitochondria to be destroyed such that those with a lower membrane potential are more likely to undergo autophagy.

The cells then replicate the remaining mitochondria and those, therefore, have a similar efficiency to the remaining mitochondria (Mitochondrial Membrane Potential - ΔΨM).

Hence each cycle of mitophagy makes the average mitochondria more efficient. Then as time goes the body makes the mitochondria less efficient through damaging the mitochondrial DNA.

Hence the effects of a single cycle of improving mitochondria will last. There is then a more complex question which is the balance between repeating the cycles of improving mitochondria and aiming to recycle a higher proportion of mitochondria, but less frequently.

3 Likes
#65

I don’t think it works like that. If it were so clearly beneficial, the body would have evolved to have more mitophagy at baseline. However, it has its downsides like everything, and is tightly regulated.

1 Like
#66

This comes down to the question as to whether or not evolution at times sets the average lifespan at a lower value.

I think the evidence is clear that from an evolutionary perspective at times longer lifetimes make a species less fit. I wrote about it here.

3 Likes
#67

Isn’t the hyperfunction hypothesis in aging that a young body did have more mitophagy, and “aging” results in less autophagy of all types due to upregulated mTOR? This was the first idea I read about as to why rapamycin slowed aging. And cycling rapa (1x/7-14 days) would allow for a periodic “spring cleaning” to clear the old proteins that the older body wasn’t recycling properly.

Has this hypothesis fallen by the wayside?

4 Likes
#68

Hyperfunction is still around as a hypothesis.

3 Likes