Thank you for kind words. This is hard won advice, I hope it will be of some use. Looking back it's frightening how fast our life comes and goes, with two decades of learning just to become prepared for two decades of peak adulthood, to have some chance to make sense of it all.

About metformin. I'm neither a doctor nor a biologist, but if life science jobs paid more, I'd heartily studied for a bio degree and worked in this profession. I'm a slightly educated gentleman who has read his Molecular Biology of the Cell and some hundreds of scientific papers of varying quality. It's my hobby.

While it is true that there is a vast universe of "dietary supplements" that do nothing reliably measurable in homo sapiens, and then there are some legit FDA-approved drugs that don't work as intended in most individuals of homo sapiens either, I think there are varying degrees of evidence to support the claim that some approaches to life extension do work, if slightly, for many average human beings. And then there is an interesting question of increasing healthspan, not just lifespan.

There is a spectrum of quality of evidence, with gold standard being high-powered double blind randomized controlled trial, followed by lower-powered RCT studies, followed by not-really-double-blind studies, followed by replicated large observational studies, small observational studies, and then studies in nonhuman primates, mice, worms and yeast cells. Even this evidence is not ideal, given financial incentives, replication crisis, publication bias, etc, but still.

In my more or less informed opinion, compared to other approaches for life extension in homo sapiens, metformin has shown that it lowers all cause mortality in humans (see RCTs, look at Gwern's review of metformin), both diabetic and non-diabetic. Given that metabolic syndrome prevalence approaches ~50% for people older than 60 in US, I think the case of metformin for life extension becomes even stronger (given it can likely prevent the onset of metabolic syndrome which lowers healthspan & lifespan). So, especially if you have some relatives with obesity/metabolic syndrome, taking metformin to have a chance of escaping this fate is a no-brainer for me.

There are some caveats: some quarter of people (myself included, I have to look for other ways due to personal incompatibility with metformin) do not tolerate metformin, because it interferes with digestion, and of course some people won't benefit from it or may even be harmed by it (though it's a very safe drug, as far as drugs go).

Generally, our fate is a product of GxE/genetics x environment/nature x nurture, and a case could be made that for a minority of people with exceptionally good genetics (here, related to lifespan, which is moderately heritable) most pharmacological interventions would ruin this fine-tuning. But I think that for vast majority of people, myself included, our genetics is not optimal (in absolute sense and for our current urban environment) and at best we can hope for a fate of our ancestors, regarding lifespan, intelligence, and common illnesses, if we do not change our environment (incl. pharmacologically).

To have a chance of having a slightly better biological fate than my ancestors, I research human biology/medicine and apply some findings to myself, understanding that this implies some responsibility & risks. Other people may choose to have a similar hobby, or to find something better to do. That being said, to look at one's biomarkers (for example post-prandial glucose, liver enzymes, vit-D levels, iron levels, etc) and to apply some non-drug methods to bring them into the green zone wouldn't be risky at all.

... If at this point there is still interest in deeper route, here are some starting points for research:

1) The Book http://gen.lib. rus.ec/book/index.php?md5=44EA074D6F741D2 F1FA1E005775F361E (could be incomplete)

2) scholar.google.com & sci-hub (could be biased)

3) Overviews of the topic from other hobbyist researchers https://nintil.com/longevity/ https://nearcyan.com/supplements/ (could be incorrect)