Anti-aging drugs rapamycin and metformin decrease iron.
Rapamycin and metformin are the most touted drugs with the potential to increase human lifespan.
The noted scientist aging research Vladimir Anissimov says that in metformin, we may finally have an anti-aging drug. Metformin is currently undergoing a clinical trial for anti-aging purposes.
Another noted scientist of aging, Mikhail Blagosklonny, believes that “rapamycin will become the cornerstone of anti-aging therapy in our life time.”
There’s been much speculation and research into how these drugs can extend lifespan. It’s thought that metformin acts by lowering glucose and insulin levels, and rapamycin by decreasing activity of mTOR, the cellular growth mechanism that also drives aging.
But it turns out that both of these drugs also affect iron, dramatically.
Metformin
Metformin is the most-prescribed diabetes drug in the world. It’s a derivative of a plant whose activity has been known for hundreds of years.
In women with polycystic ovary syndrome, an illness in which insulin resistance plays a role, metformin lowers ferritin in only 3 months of treatment.
Below is a graph of ferritin levels in women treated with metformin. (Top graph, metformin is open circles.) Ferritin declined dramatically. Another drug (closed circles) had no effect.
Luca Mascitelli suggests that improvement in polycystic ovary syndrome with metformin treatment is due to decreased iron levels. He also suggests that the improvement in non-alcoholic fatty liver disease with metformin is also due to a decrease in iron. Metformin probably does this by inducing a decrease in dietary iron absorption.
Rapamycin
A common side effect of treatment with rapamycin, which is used for transplant patients, is iron deficiency anemia. Those patients on a different drug did not become anemic.
Rapamycin’s best known mechanism in life extension is the reduction in activity of mTOR (the mammalian target of rapamycin). Yet iron activates mTOR, and iron chelators deactivate it. Perhaps rapamycin deactivates mTOR through its actions on iron.
Iron promotes aging
Iron promotes aging. I’m going to be going to my grave (ha ha) saying this.
Is it possible that the main anti-aging benefits of both metformin and rapamycin are due to lower body iron stores? Yes.
Is it possible that you could get all the benefits of these drugs just by lowering body iron stores on your own? Yes. Is it probable. Yes, I believe it is.
Don’t wait for anti-aging drugs
You may be waiting a long time for anti-aging drugs, although some doctors will prescribe rapamycin, and more of them metformin. (OTC berberine is a reasonable facsimile of metformin anyway, and it may be even better.)
So keep iron in the low normal range; learn how with my book Dumping Iron.
23 Comments
Question, PD. How does resveratrol work?
Resveratrol increases mitochondrial biogenesis and appears to act like a calorie restriction mimetic.
As always PD, another interesting and thought provoking article. Thanks!
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PD, Excellent post ! My own GP has declined to provide a script for metformin. So I use Berberine.
There is so much resistance here to the idea that Iron causes aging; it’s dismissed out of hand or if thought about at all, said only to be a ‘correlation’. It’s bizarre.
My brother with ferritin iron levels of 369 was said to be normal by his GP a week or so ago. And my own GP is strongly suggesting not donating blood even though my own ferritin level is now up over 100. Needless to say, we are both ignoring them.
Hi Bill – I wonder why your GP won’t prescribe metformin? It actually extends lifespan, lowers blood sugar – I bet he’d give you a statin though, or Oxycontin.
We had exactly that conversation PD about 9 weeks ago PD. And I declined the statins which put him out somewhat. His reason for not giving a script for metformin was simply that it ‘only for type 2 diabetics”
.I guess he has no updated his own professional training recently.. He is the owner & manager of the practice with 5 other doctors, 2 nurses, plus reception & office staff. But I am working on him. I formally presented him with my list of anti-aging supplements last time – including Berberine in place of metformin. ;- )
rapamycin is really expensive. Would you reccomend metformin for iron and weight loss?
Metformin seems a bona fide life extension drug. Berberine might work equally as well, no scrip needed for that.
Thanks PD!
Have you heard of and / or looked into a supplement called MitoQ with respect to anti-aging?
https://www.mitoq.com/mitoq-5mg-capsules-60.html
Yes, and I’ve taken it myself. I suppose if it were cheaper I would have kept taking it; I didn’t notice any difference when I did so. The manufacturer sent me a sample of 3 bottles, and I ended up giving 2 of the bottles to my 95 year old mother. I figured she could use them more than me. More seriously, it’s a mitochondrial antioxidant, and while these can be very good, my feeling is that for me, I already exercise intensely, keep iron low, and eat low carb (sometimes ketogenic), and I think those are the most important things for mitochondrial function.
Very interesting post (as usual)! The last comment you made in it brought a further question to my mind.
“OTC berberine is a reasonable facsimile of metformin anyway, and it may be even better.”
Does berberine also cause a reduction in bodily iron stores, by any chance? Is there any evidence on that one way or the other?
Indeed, berberine chelates iron, “marked capacity of berberine for iron binding, suggesting that its action as a peroxidation protector may be related to its iron binding capacity”. Link.
Great article as always, PD. In your research, did you get an idea into how much Metformin reduces glucose levels? My HbA1c is in the mid 5s. I’ve got a good doctor that is aggressive about reducing blood sugar and gave me a script for metformin but I’m having some negative sides, namely fatigue. I already lift and eat clean on the low-carb side. Curious if you would hazard a guess at what the upside would be.
Edit: I guess I’m curious what I could get my a1c reading to using metformin.
Thanks, Jason. I really couldn’t say, only that metformin is the most effective and widely prescribed diabetes drug. I haven’t heard that it causes fatigue. My only “experience” is reading the research and talking to people who have taken it, since I’m not a doctor.
great article! Is there any study or detial article you could point me to get Rapamycin prescribed from my doc?
great article! Is there any study or detail article you could point me to get Rapamycin prescribed from my doc?
It will be difficult to get a rapamycin prescription, but some people are doing it. Very good article about it here.