Should Rapamycin be Prescribed Ubiquitously as an Anti-Aging Supplement?
Should rapamycin be prescribed ubiquitously as an anti-aging supplement? That is the question the authors of this commentary ask after a short overview of what is known of the beneficial effects of rapamycin on mechanisms relevant to aging. Research into inhibition of the two mTOR complexes, mTORC1 and mTORC2, via compounds such as rapamycin, is well funded at the present time. Numerous companies are attempting to push mTOR inhibitors through clinical trials. It is perhaps the largest outgrowth of research into the slowing of aging produced by the practice of calorie restriction, in which benefits are largely mediated by an increased efficiency of the cellular housekeeping processes of autophagy. The question at the end of the day is whether the effect sizes here are large enough to chase hard, in comparison to those that can be obtained via exercise or calorie restriction, given that we know that exercise and calorie restriction have only a limited effect on the shape of human aging. We should aim higher.
mTOR (mammalian target of rapamycin) plays a significant role in age-related stem cell dysfunction through various mechanisms highlighting its potential as an anti-aging target to rejuvenate stem cell function. In fact, mTOR regulates many of the hallmarks of aging. A breakthrough study in 2009 showing the lifespan extending properties of rapamycin in genetically heterogenous mice led to significant research into rapamycin as an anti-aging intervention. Since that time, rapamycin has been well studied in aging and age-related functional decline mainly through the modulation of autophagy, mitochondrial function, insulin signaling, and senescence.
TOR is a heavily conserved serine/threonine kinase with homologues in several eukaryotes from yeast to humans, highlighting its importance in cellular processes. The mammalian version, mTOR exists as two distinct complexes, mTOR1 and mTOR2 that are structurally and functionally different. The mTOR1 complex acts as a central nutrient sensor and regulator of cell proliferation, growth, and survival. mTOR2 activity is usually preserved during acute rapamycin treatment but prolonged exposure can reduce mTOR2 activity as well. Hyperactive mTOR activity with aging seems to have deleterious consequences in somatic stem cells, especially muscle-derived stem cells.
Rapamycin and other compounds have been demonstrated to have significant senotherapeutic effects (i.e. selective ability to restore or eliminate senescent cells). Not only has rapamycin has been demonstrated to reduce senescence in muscle-derived stem cells by our group, but others have demonstrated that blocking mTOR reduces stem cell senescence and associated secretory phenotypes.
Should rapamycin be prescribed ubiquitously as an anti-aging supplement? There is certainly a preponderance of evidence demonstrating the safety of rapamycin in healthy and aged humans that has been well reviewed. Since its approval in 1999 by the FDA, rapamycin has been used by millions of patients with very few mild but reversible side effects. However, one possible strategy is likely intermittent treatment at higher doses for prolonged periods of time. We additionally propose that a combinatorial approach may be in order to target senescence at multiple nodes (inhibition of anti-apoptotic pathways and mTOR) directly through the use of multiple senotherapeutic agents such as fisetin and rapamycin. Overall, the plethora of preclinical and clinical data using rapamycin strongly suggests that targeting mTOR and/or senescence is a promising therapeutic strategy to mitigate aging-related phenotypes and restore stem cell health and function.
Just for example, a couple of weeks ago I did a 5 days water fast. As an effort it was non-trivial, much harder than popping a pill. Probably the benefits would be similar to being on rapamycin for a couple of months. I am starting considering obtaining some on my own. While doctors are quite liberal at prescribing metformin only for some of the risk factors , they are quite careful with rapamycin since it suppresses the immune system response. The question is also how much does it slow the age-related degradation. For example, if a hollywood celebrity takes it will it postpone the need for plastic surgery at all, for a year or even 5 ?
Exercise and fasting come for free, with no negative side effects if you do it right.
@Stephan
They both require effort and dinner degree of financial independence. Of not done right they can lead to damage , especially if you are old.
Popping a pill is 100 times easier. Somebody has said that if you could bottle the exercise as a pill or a potion ( like in Harry Potter, for example) and the said pill combines both the benefits and side effects of doing exercise it would have hard time passiing the FDA approval for being to dangerous.
Besides there might be some synergy of fasting and using rapamycin or metformin at the same time, as a way to enhance the effects of reduce the fasting times.
I'm very irritated by all the mTor inhibition talk. The mTor complexes have very important functions in e.g. muscle protein synthesis and activation of insulin receptors.
Permanent inhibition surely has deleterious effects esp. non-selective inhibition of mTorc1 and mTorc2.
Fighting chronic mTor overactivation in aged individuals should be possible at more upstream targets like treating senecent cells, fixing cell metabolism, fixing mitochondrial dysfunction, ...
For older folks, worrying about optimal nutrition, exercise, sex and growth hormone levels, and senescent cell reduction probably makes more sense. For younger folks, as Reason noted, you should probably be aiming higher than the few extra years mTor inhibition might get you. imho
https://www.reddit.com/r/longevity/comments/i6rq0n/update_on_rapamycin_treatment_for_dogs/
Two small Poms were given Rapamycin late in life in 2016 by their owner and this was covered by CNN. They both had a 25% increase in lifespan and health span and one is still alive at 19+ years. It's interesting that the 25% increase closely matches what has been seen in mice on Rapamycin. It seems to scale well with larger more complex mammals. N=2
Unfortunately we still don't have a copy m for inhibition pathway protocol. Rapamycin alone could single handled give a body of Couple of years of healthspan , and if combined with Senolytics cold at up to 5 more years of healthspan and good knows how much to lifespan. If we're count the number of old people introducing of rapamycin combined with Senolytics cold easily busting 5 billion adjusted man years of life for the whole humanity. Not to shabby. .
I have taken rapamycin for 4 1/2 years. It worked out so well for me I told 500 of my best friends to take it. I talk with them frequently and they are doing quite well.
I think this last post was made by Dr. Green and I would be one of those 500 folks he talks about. He has definitely changed my life for the better. Since taking fisetin, metformin and rapamycin I have noticed a big difference in my health. My stamina and heart health has improved dramatically and I have lost weight around my mid section for the first time since my twenties. I'm surprised more people aren't taking it. For anyone who is interested in taking this wonder drug please google it and read as much as you can about it. I read about it for months and did a lot of research before getting the prescription.
@John. Any link on Dr. Green?
Hi, I've done a tremendous amount of reading about rapamycin. I suspect a good plan would be to take it once a week for months, slowly working up to only the maximum personal dosage, which would be the point where an individual has any adverse symptoms, and backing off slightly.
Possibly with blood test, triglycerides would increase, at which time you could stop for a month, and then begin again. Possibly minimal statins could be added to the plan.
The big question I have, is how long should you continue this intermittent routine to see maximum or at least substantial benefits? One, two, three, years or for life? I've not found That answer in much research.
Cheers!
I started taking rapamycin a few years ago, after I discovered Dr. Green's website and this treatment option for the prevention of Alzheimer's disease, which runs in my dad's side of the family. I am very pleased with my treatment effects overall and have no intention of stopping, but I do have a concern about how intermittent rapamycin affects bone health. During Covid I cracked a tooth, had to have it extracted, and opted for a dental implant. During that procedure I 1) rejected the bone graft, and 2) seemed to have a problem with bone regeneration. After rejecting the bone graft, the dentist indicated he was concerned that I might not be a candidate for an implant because he saw very little vascularity in the bone structure. He stitched up the wound, and told me to come back in a few months. I stopped taking rapaymycin for a year throughout the process and ultimately completed the implant process, but there was still bone loss around the tooth and I'm a bit concerned about whether the implant will hold up.