On Rapamycin: "The known adverse effects caused by sirolimus and marketed analogs at the doses used in transplant regimens, especially the increased risk of infection due to immunosuppression, as well as dose-dependent metabolic impairment, make it unlikely that chronic, long-term treatment with sirolimus could become a widely used anti-aging agent."

Sounds more than a little dangerous, unless you have an illnes like Lupus that activates mTOR, and even then I'd be nervous taking this drug without expert medical supervision!

On the upside, my partner has a Lupus-like autoimmune disease, so this drug will be an interesting one to track.

Yeah, I have it in a different section on my page mostly for that reason. It's not something I'd ever encourage people to 'just take', in the way I might some simple vitamins or minerals or so on that they might need.

Personally, I do think it can likely be taken pretty safely if monitored reasonably, and I am pretty hopeful for it as well. But it's true it's a serious drug so it shouldn't be messed around with as if it's a game.

Interesting you take rapamycin and a bunch of other stuff thats supposed to extend lifespan. I wish to see if you live longer but I'll probably die first lol.

Serious questions: have you experimented with calorie restriction? Clearly thats THE method that works in every species. Second question: do you battle with depression? My current hypothesis is that any life extending drug will also inevitably lead to depression given the links shown between the sirt1 pathway and depression (also potentially as an evolutionary check but that's just me throwing ideas out).

Yes, I generally have been doing quite a bit of intermittent fasting, fasting, and caloric restriction. But not very strictly so, only sometimes.

I have before, but I would say it's not too bad right now.

Interesting. I'll keep following you to see how things progress!

How are you getting rapamycin?

I'm interested in it's benefits for autoimmune diseases but it seems quite expensive (in the US).

Some doctors will prescribe it for off-label use, but this is pretty rare. It's possible to purchase it from overseas websites as it is not scheduled, but this is technically not legal, and it will still cost quite a bit out-of-pocket. With that said, it can definitely be potentially dangerous, and dosing+frequency would have to carefully be paid attention to, as well as monitoring results via blood tests imo, and having done extensive research and so on. I wouldn't suggest anyone just purchases it to experiment with it without being very careful and having a high appetite for risk. But other things like glycine or spermadine or vitamin D or magnesium I'm much happier to gleefully suggest to people.

Any other advice for folks? What do you think of NR?

I personally don't buy that NR does much. I think there's some interesting hints that we're getting close to finding out useful things, but I haven't found much that personally convinced me about NR and those related to it. Agree with what I hear on podcasts like Peter Attia about it, but I think maybe some day soon we'll find something promising in that area.

It's a hard area to give advice in since everyone is different, so I can't really offer much besides that I think for the best return, someone has to spend a lot of time doing their own research and testing and so on to find out what works for them

Do you take each Vitamin individually, or do you take a multivitamin?

Do you make an effort to get large doses of these things from food first?

Individually. Sometimes a few things are combined when a good option is available, but generally multivitamins don't give me what I want in the doses that I want.

Since I tested all of my blood metrics beforehand, it's unlikely the market would have a 'perfect' vitamin for me. Especially since most of what I like to take isn't technically a vitamin.

My diet is currently pretty un-optimized, so although I would prefer to consume a lot of things via diet, it's not guaranteed at all. But the extra bio-availability and such is likely nice

Id be curious what it would look like if you tested your blood now, stopped taking them all, and radically modified your died, what kind of results you would get in a couple weeks.

Daily intake of, tomato juice, kefir, sardines, salmon, spinach, sunflower seeds, pumpkin seeds, pistachio, eggs. You could probably get a whole days worth of food into a snack, a salad, and a soup.

I wish it was easier to do intensive tracking of everything like that, but it's definitely a lot of work. Some supplements I have very clear before+after results, with the only probable cause being the supplement (e.g. vitamin D or magnesium), but a lot of others are hard to test, control for, find biomarkers for, etc.

I do know there are a few people in the area that log literally every substance they eat in terms of grams, and then correlate it with all of their blood metrics, and use that to try to optimize each blood metric for what correlates with the lowest mortality rate. It's interesting, but this stuff is unfortunately a lot of work for average people to attempt. Here's a great example: https://twitter.com/Nearcyan/status/1282042301980835842