Late life Metformin shortens lifespan?


I think this pushes us towards Acarbose usage in later life.


“This article is a preprint and has not been certified by peer review”

I’m no advocate for Metformin (for non diabetics) but I think it’s important we critically evaluate the source of information. Journals vary in their prestige and are often an indicator to the quality of the research…


Is this a Russian paper?

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Isn’t the aim to not have many of these “old cells” as a result of autophagy?

To tell the truth, I did not check who the authors are. If you read it, I’m sure it’s there. Was posted today on Twitter.

I’m not a diabetic, but I take it because of borderline glucose. Metformin is hard on my kidneys, so I may reconsider taking it as well.


Not gonna base much on a worm study. Still not a fan of Metformin in non diabetics.

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This was a pre-print from December 3, 2019. Do you have any idea if it was ever accepted for publication in a major journal? I can’t find any evidence that this study was ever accepted.

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The benefit/risk just doesn’t seem to work for metformin when it comes to life extension. It’s too bad because used to be a big fan. Changed my mind completely on it 2 years ago and nothing since has swayed me otherwise.


This is the same study I believe.


Matt Kaberlein’s lab has found Metformin extends C. Elegans lifespan by 15% consistently. It’s the whole basis of the wormbot.

Can you cite some? Because this study specifically focuses on late life metformin. Another study showed that in late life metformin is effective in extending life only in low concentration, but not in medium and high… Matt Kaeberlein doesn’t state that any of the studies that extend C. Elegans life were done late in life in this interview. Of course anything done in C. Elegans is difficult to extrapolate to human life and even what would be “late life” in humans?

Looking at metformin studies I found this, which is really interesting, probably already posted somewhere on this forum… but sounds really optimistic and it would make metformin a worthwhile medicine to include in any life extension regimen. You need a healthy brain if you want to get old.

Good find! I believe it is the same study. However, it plainly states that: "However, the metabolic response of a non-diabetic cohort to metformin treatment has not been studied."

I took metformin for decades with no ill effects that I know of. I no longer take it because there has been other evidence that it is probably not good for older people. My doctor told me not to worry about taking it at my age because any adverse effects from increased fasting blood levels won’t show up for many years. I have been on and off of acarbose but following the advice of RapAdmin, I have cut out most wheat products, but not pasta.
Either my gut bacteria has changed or pasta products don’t trigger an excessive gaseous response in me. I have noticed that taking acarbose in the morning on an empty stomach lowers my fasting glucose at least as much or more than metformin.
Bottom line: I still believe in metformin with rapamycin for life extension. Though, I know some folks can’t tolerate it.

Right now I take acarbose before every meal even if it is relatively low carb. I am trying to keep my A1c within bounds despite taking rapamycin.

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C. Elegans lives 12-18 days only. Metformin is well known to increase C. Elegans lifespan by 15% based off of at least 100s of trials by the wormbot alone. Based on my knowledge of the subject, this paper doesn’t warrant any further time spent.

Yes, what exactly is late stage life for a worm that lives 18 days tops? And of course what works for worms doesn’t always work for humans. Metformin is a well-studied drug.

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From this study I would say the older the organism the lower the dose that is working to extend lifespan. This is confirmed by several studies. But this is the only study that found that metformin is toxic in late life. (Even for humans it is not recommended over the age 80, but for kidney function not other toxicity…)

To address the outcomes of metformin treatment at different age, we treated young adult (3 days old, day 1 of adulthood), adult at the age of reproduction decline (day 4 of adulthood), middle aged (day 8 of adulthood) and old (day 10 of adulthood) wild type C. elegans worms with different doses of metformin – 10mM, 25mM and 50mM. 50mM metformin is the common dose used to induce lifespan extension in C. elegans while 10mM is the lowest dose linked to reproducible life extension in this model in previous reports (Cabreiro et al., 2013; Onken and Driscoll, 2010; Pryor et al., 2019). We found that metformin treatment started at young age (days 1 and 4 of adulthood) extended lifespan of nematodes at all doses used (Figure 1A and Figure S1A). Within treatment initiated on day 8 of adulthood, the doses of 50mM and 25mM metformin reduced median lifespan but extended maximal lifespan consistent with previous observations (Cabreiro et al., 2013) while 10mM dose was longevity-extending with no detrimental effects (Figure S1B). Strikingly, on day 10 of adulthood metformin was toxic at all doses used with a large proportion of drug-exposed animals dying within first 24 hours of treatment (Figure 1B). Our first experiments in nematodes thus revealed an evident age-dependent decrease in metformin tolerance which culminated in late life toxicity of all metformin doses tested, indicating possible safety risks of late life metformin administration.


Those are valid points. Again, I think, if anything, this points us in the direction of using Acarbose.

Since I am middle-aged and taking Rapamycin, I will probably continue with taking both Acarbose (100 mg each meal) and Metformin (500 mg at night) to get the benefits of both.

However from use, I consider Acarbose far superior. It’s the only intervention that has successfully caused me to lose weight.

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I’m also thinking about switching from Metformin to Acarbose, but unfortunately my doc doesn’t want to give me a script.

I get mine from India.
I bought mine from Jagdish, but got responses from many other Indian vendors for approx. the same price.

IANAD but my physician told me that while Acarbose and Metformin are both excreted through the kidneys the risk of Acarbose accumulation in those with kidney issues is higher than metformin due to the frequency of use, ie; three times daily at large doses versus once daily or twice daily with Metformin. I cant find any studies that confirm that but it makes sense practically.
High amounts of either could lead to lactic acidosis.