Metformin inhibits mitochondrial adaptations to aerobic exercise training | Hacker News Reader

Metformin inhibits mitochondrial adaptations to aerobic exercise training

ncbi.nlm.nih.gov

47 pointsevo_922 comments

Context: Metformin is a simple, very safe, and very common diabetic drug that appears to improve all-cause mortality and have some positive health effects in the average person, even if minor (such as improving blood glucose levels and insulin resistance), thereby slightly lengthening human lifespan and improving the process of aging. For this reason it has been touted as an anti-aging drug by many, and is taken by many non-diabetics for this purpose.

However, there have been more studies surfacing recently that show that it can make exercise less beneficial, of which the link in OP is a piece of evidence in favor of this.

For those interested in other interesting substances in this area, I suggest looking into Acarbose and Rapamycin, but there's many others that seem pretty cool, even if highly speculative. Also adding after reading a child comment to this, Peter Attia is one of the many great people worth following in this area, with a very high-quality information-dense podcast.

There's more to exercise than just mitochondrial adaptation... Presumably by inhibiting that, yet still demanding some adaptation from your body (by taxing it with strenuous exercise), you're promoting other adaptations? It might be beneficial somehow. Also, AFAIK more active mitochondria might not be a good thing (more reactive oxygen species damaging your cells, more chances of mitochondria mutating maybe causing cancer).

Anyways, I'm not a professional, just a hobbyist follower of anti-aging community. For what it's worth, Peter Attia, an anti-aging doctor whom I follow, recently said he stopped taking metformin after having taken it for years.

> Peter Attia is one of the many great people worth following in this area, with a very high-quality information-dense podcast.

One of my favorite podcasts, and I had listened to every episode until recently. (no longer driving during the pandemic, and that’s when I used to listen to podcasts)

The information density is awesome, it really makes me think trying to keep up with it, and over time I start to understand a bit more.

Good for me as I don't exercise. I'm not sure why people believe that exercise is beneficial for life span - it is as much beneficial as it is detrimental. I see those people jogging for "health" right next to car exhausts and I keep scratching my head. If you look at the longest lifespans, you won't see any athletes at the top. In fact, you will see a lot of scientists who mostly live sedentary lives, but most of them do walk regularly, that's a fact, although not really an exercise. Aerobic exercise is the single biggest source of ROS', which is part of its benefit - it can kill pathogens, it can occasionally have a hormetic effect. Outside of sex, I don't see a any proof that jogging will make me live a longer, happier life (especially when you subtract the time spent jogging). Most of the benefits of exercise can be accomplished via diet and lifestyle changes. Maybe some flexibility exercises like callanetics are worth the effort though, which can be accomplish with simple yoga.

Life span is a red herring. It's like listening to a smoker point out their grandma lived til 95 while smoking, so how bad could it be? She just couldn't walk up the stairs without gasping for breath her final 30 years.

There's a lot more to life than life span -- literally all of it. The curse of the human brain is that we easily rationalize and dismiss things like complex systems that don't have an obvious 1:1 daily payoff like exercise.

You know exercise is good yet since you don't personally perceive its day to day impact on you, then it must be useless. Even though it might improve your lifelong mood 10%, prevent that hypothetical cancer from metastasizing in 10 years, make you 10% less irritable, make your dick perform for 10 years longer than it's going to now, be the lynch pin in all sorts of beneficial branches that life can take even on molecular levels that you will never be able to truly perceive. This is basically the state of the art of our understanding of exercise -- it's the only panacea we know of.

Seems mighty convenient to convince yourself that something that's hard and requires willpower and that almost everyone fails at is in fact unnecessary after all. I would be a little more defensive against such obvious sweet self-deceptions.

> Outside of sex, I don't see a any proof that jogging will make me live a longer, happier life (especially when you subtract the time spent jogging).

Still a valid use case for cardio training IMHO.

Yeah, but at least it's real fun, unlike jogging. :D

I have a friend who is obsessed with min-maxing the supplements he eats including Metformin.

What's wild to me is that he doesn't even exercise. It's like we're so bored/tired of the concept of exercise that even people seemingly obsessed with various health subtopics will glance past it.

Meanwhile, I bet adding an extra run to your week does 1000x more than Metformin will ever do. A lot of this stuff seems like obsessing over the shape of your car's exhaust pipe for performance when you don't even change the oil.

I wonder how many HNers who take it are the same https://hn.algolia.com/?dateRange=all&page=0&prefix=false&qu....

Edit: On second read this seems like a harsh, debbie-downer comment. I certainly hope a drug like Metformin is a magic pill you can take independently of the rest of your habits. It's just that this news is a reminder that we can't yet have things for free in pill form. At the same time, we have this constant aversion to the few things that we do know work, today.

David Sinclair says he takes metformin on his rest days. It might be acting like a substitute for exercise on such days but exercise is still needed. He discussed it in a YouTube interview with a fan several months back.

Problem is, there are genetics that make some low responders to cardio for weight loss (see the University of Bath study). Years ago, I built up from never really running to 6+ miles at a stretch... but soon hit a plateau that I could never move below until discovering keto 10 years later.

Really? What is that run going to do for your lifespan?

First example that pops into my mind to address your question:

Running builds muscle and improves balance (among other things). Many people late in life die from head injuries caused by falls. I have a better chance of living longer and healthier with a stronger body.

I'm primarily concerned with healthspan over lifespan.

Goal to be sharp and as healthful as Jack Lalanne at 95: https://www.youtube.com/watch?v=AkdYrAQJu6g

Yeah, I know he died a year later from pneumonia. He mentions his ego in the video as well.

To be clear, that's a weekly run. Just like we're not talking about a single lifetime dose of metformin.

As for the benefits of exercise with very few downsides, the abstract mentions some.

I really think that any effective anti aging therapy is going be something that is specific to, or based on information from, the specific patient. Here’s my logic: if there was some molecule or hormonal tweak that would defeat aging in every individual that was given it, then the improvement would be heritable. And some organism at some point in earths evolutionary history would have found it by now, which means we would know about it. So, there likely is none.

So, if there is an anti aging therapy of some kind, it must be something that is not a simple heritable molecule to be synthesized. That means some kind of genetic or stem cell therapy.

I’m not a biologist though so ymmv.

Edit: on that note: https://med.stanford.edu/news/all-news/2020/03/old-human-cel...

Genes for living longer reproduce in a population only if they enhance fertility rates, but I suspect throughout history humans have been food constrained, and so there was never an opportunity for an older couple to have another baby when the younger couples were “maxed out” with babies already. Given food scarcity, living longer only means the clan needs more food, which hurts the clan’s overall fertility.

In general, you don't want to take anything if you can.

Drugs usually inhibit biological processes. Metformin inhibits mitochondria. This can be good for diabetes and good for aging, but it depends. Hopefully your doctor understands when to prescribe it.

What do you mean by "inhibits mitochondria"? Actually, the lack of proper mitochondrial QC is the biggest culprit of chronic disease. Cycling from mito fission to fusion is the best approach to fix this and that's why people use metformin wisely in protocols, which do the cycling.

With that said however, the average American diet is generally messed up enough that a lot of substances could benefit them, because there's so many existing problems that have room for improvement which are created by bad diet.

With a perfect diet, the amount of drugs you may want to take would definitely go down, perhaps even to zero.

Given that we’re talking about longevity extension here, that “perfect diet” would have to be perfect indeed, to make you immortal.

How about fixing the crap average american joe eats starts with the crap itself, rather than some substance that would magically fix bad effects?

It can be far from perfect, nobody actually eats that, just normal food, in normal portions, like our ancestors ate.

For many europeans the scale of how crappy US food can get while also being calorie-dense is hard to comprehend. Its not like US is a 3rd world country where most of population can't afford better - most simply don't even try.

Not sure why this is getting downvoted--it's a fundamental truth. Especially given how truly little we understand about biology.

Endless. Eat well, cut carbs, fast now and then, exercise AF. The rest is a prayer.

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