Rapamycin: One Drug, Many Effects (2014) | Hacker News Reader

Rapamycin: One Drug, Many Effects (2014)

cell.com

The speed of research in this area is fast enough that I don't think it's worth reading a review from ten years ago. My understanding is that interest in rapamycin has faded a bit since then, can anyone confirm this?

This article is out of date; lots of progress has been made since then. The NIH-sponsored Intervention Testing Program showed conclusively and multiple times that rapamycin is able to extend the lifespan of mice about 10%; and more recently the lifespan of macaques was also shown to be extended. It works by fooling your cells into thinking there's no nutrition available, by inhibiting the "MTOR" receptor. It's well known that "dietary restriction" extends lifespan in most life forms. The doses needed are lower than the usual FDA-approved use of rapa for preventing rejection of transplanted kidneys, and bio-hackers have not encountered lots of side effects. Probably the best hope for increasing health-span, which matters more than life span. Since it's in the public domain, there's not much hope for getting large studies done to prove efficacy, but the "Pearl" study recently showed a good safety profile. Also, the Dog Aging project is in progress, enroll to increase the lifespan of your dog (or not, it's double-blind).

See https://www.rapamycin.news/

If you're curious about rapamycin, I recommend checking out Matt Kaeberlein's podcasts on the subject (among others): https://www.youtube.com/@optispan

He's been researching the subject for years and is measured and balanced about the value of using it (he is a proponent).

I'm planning on starting soon because the clock is ticking and I can't wait a couple more decades for more research to come out.

This is not medical advice, but I have used rapamycin for an as of yet undiagnosed autoimmune condition (likely psoriatic arthritis vs rheumatoid arthritis) and it almost completely cures the condition while taking it, at the cost of mild-moderate hair loss and acne (which recovers on cessation of the drug). I cycle on and off rapamycin every few weeks to minimize side effects and whatever unknown long-term risks.

What's your dose regimen like?

It's varied. Taking as little as 1mg per day with 1 day off worked well. But so does spot treating with 4mg every week or so when symptoms flare.

my opinion is that targeting mTOR is fruitless because it's so broad and integral to life that it's like a self-righting ship or trying to sink a life preserver.

as described in the conclusion: "This may be explained by the inability of rapamycin to completely block mTORC1-mediated signaling events, the presence of several feedback loops, and the upregulation of compensatory pathways that promote cell survival and growth."

targeting mTOR is like saying "let's write a bug that takes down Linux"... the community isn't going to let that happen

Can you elaborate?

It seems to be not fruitless in all the organisms that it has worked on so far.

Listen to the podcast on this drug from radiolab. The story on its discovery is literally riveting.

https://radiolab.org/podcast/dirty-drug-and-ice-cream-tub

I have no other words.

We spent an unfortunatley long time blaming fat people for being fat, which lead to an underinvestment in metabolic research. We're in the early stages of breaking this puzzle and it's fascinating. (No. I maintain a healthy weight to a fault, forgetting to eat if I miss exercise and gaining little weight irrespective of diet.)

It's everything. It can work against cancer and cause cancer. Make you age slower, but kill you faster.

It's immunosuppressant. Suppressing immune system for completely health person decreases inflammation that comes with aging. Suppressing immune system makes person more vulnerable for infections (flu, sepsis, herpes, ...), and wounds heal slower. Also cancers.

Humans are already among the longest living land mammals and rank pretty high among all large animals land or otherwise. We're already evolutionarily optimized for longevity.

Trying to push further out seems to run into a lot of trade-offs. It seems from what I've read that there are mechanisms that cause aging but also are defenses against cancer, like telomere shortening which imposes a cellular division limit. The immune system causes inflammation which causes aging but turn that off and stuff eats you. And so on...

Not saying it's not possible, just that it's going to require more than tweaking a few knobs. I highly doubt there will ever be a "longevity pill" that radically extends life span, though obviously there are medications that can have some positive effect especially on health span. Anything radical like taking the average well past 100-120 years is probably going to require genetic engineering or radical (and invasive) regenerative medicine.

It may leave someone more susceptible to bacterial infections, but the idea that it leaves a person more vulnerable to cancer is unsubstantiated. Tumor growth is dependent on the growth signaling mechanism that Rapamycin suppresses, which is why it has been suggested as a potential cancer therapy.

As I said it can prevent and cause cancer with different mechanisms.

1. Immune system kills cancers. T cells attack and try to destroy the cancerous cells and Rapamycin weakens T cell reactions.

2. Rapamycin inhibits the growth of several cancer cell lines.

The discovery of rapamycin sounds like something a Joe Rogan guest would pontificate about. What an interesting drug.

Joe Rogan only shows interest to conspiracy and contraversy, so I don't think he would invite a guest to pontificate about science and medicine that could be benefitial to humankind.

But it is an interesting drug:

>> The protein, now called mTOR, was originally named FRAP by Stuart L. Schreiber and RAFT1 by David M. Sabatini;[6][7] FRAP1 was used as its official gene symbol in humans. Because of these different names, mTOR, which had been first used by Robert T. Abraham,[6] was increasingly adopted by the community of scientists working on the mTOR pathway to refer to the protein and in homage to the original discovery of the TOR protein in yeast that was named TOR, the Target of Rapamycin, by Joe Heitman, Rao Movva, and Mike Hall

Just googled "Joe Rogan rapamycin". Seems like he talks about it in multiple episodes with (at least) doctors Peter Attia and David Sinclair.

Not surprising. Rogan is also an aging gymbro who would definitely be interested in anything that might boost performance to youth-like levels.

I just have a bad taste for David Sinclair after his whole debacle of cashing in on company and making billions of false promises. He was also sacked from harvard for this https://longevity.technology/news/david-sinclair-resigns-as-...

He also blocked Brad Stanfield (who, I kind of look up to for a lot of health research)

Hard to take him seriously after all this.

Joe is a very curious person, so it goes in that direction sometimes just because it's interesting to think about.

He's had biologists, virologists, bio-hackers, engineers, doctors, regenerative farmers, psychologists, wild life experts, physicists, etc.

This is from 2014. What’s the point of resharing it?

It's new to me and I've found the comments thread enthralling.

Reply on news.ycombinator.com