[irthomasthomas]

Metformin.

Research in humans suggests that metformin can impact mortality. A meta-analysis published in 2017 that included 53 different studies concluded that metformin reduces all-cause mortality and diseases of aging, independent of its effect on diabetes.

Also, combinations of Metformin, rapamycin and resveratrol, and NMNs.

Davis Sinclaire is probably the leading expert on those, now. He is professor of genetics at Harvard.

https://youtube.com/watch?v=bRWT7hVgwuM

[loeg]

Worth pointing out that Metformin has a host of unpleasant and common side effects. E.g., here's 40% of type 2 diabetics not adhering to the prescribed dosing protocol: https://joppp.biomedcentral.com/articles/10.1186/s40545-022-...

> A number of studies assessing adherence to diabetes medications in patients with type 2 diabetes have reported that metformin has the lowest adherence rates when compared with other OAAs.

[pazimzadeh]

Is it known what the mechanism is for metformin's effect on longevity?

If it's due to its ability to reduce blood glucose levels, then berberine may be another way to get a similar effect.

Berberine stimulates glucose transport through a mechanism distinct from insulin

https://www.sciencedirect.com/science/article/pii/S002604950...

Efficacy of Berberine in Patients with Type 2 Diabetes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410097/

It also lowers cholesterol

Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins

https://www.nature.com/articles/nm1135

But pure berberine is not absorbed very well in the intestines, so you need to buy a good formation for it.

Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine

https://www.ncbi.nlm.nih.gov/pubmed/20237966/

Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability

https://pubmed.ncbi.nlm.nih.gov/24607213/

The best thing might be to cook with barberries:

https://thecaspianchef.com/2020/01/18/zereshk-polo-saffron-b...

[safety1st]

This one is really interesting, thanks. I think it's the closest any mentioned substance comes to passing the "creatine test" (for whatever that test is worth; I just made it up).

(A) The body of research is, in general, large and uncontroversial.

(B) The safety profile is good. The benefits for diabetics are certainly large. Probably no drug has been studied for anti-aging effects as extensively as creatine has been for fitness applications, so I'm not sure anything can fulfill that criteria. But it seems like the present research on metformin supports a variety of positive effects for non-diabetics with more on the way.

(C) I wouldn't know whether the majority of people who are serious about anti-aging use it but it does get mentioned a lot.

Pretty positive endorsement overall!

[tysam_and]

It looks really promising. However, there are some growing concerns I believe that link it with mitochondrial dysfunction as well, if I recall correctly. Hopefully that's not the case, but it's a developing story. (It does reduce exercise output as well if someone is an athlete and cares about hat, but since it does mimic exercise in a way on a cellular level, that's to be expected I guess). :'(

[irthomasthomas]

There's always exceptions in popular medicine. No doubt a small minority of people get no benefit, or may even be mildly harmed by the medicine. But Metformin, in particular, is one of the most popular drugs in the world, and it's strong safety profile is well established. "All-cause mortality is lower in people on Metformin". So, I don't think there will be any big surprises found in its safety, but maybe we'll find that a certain minority of the population aren't suited for it.

[phkahler]

Mitochondria need proper care too. I take iodine and magnesium for asthma (which is cured) and I hear iodine is also go for mitochondria, which might explain why it's good for so many things.