Metformin and positive effects on epigenetic clocks

Any thoughts on this study?

“We found a strong association between metformin intake and slower epigenetic aging by Horvath’s clock and Hannum’s clock.”
Source: Effect of metformin on the epigenetic age of peripheral blood in patients with diabetes mellitus - PubMed


In some cases Charles Brenner can be little bit to tough in his approach but it’s a important thing he points out regarding the study that it was done on people with type 2 diabetes. We have seen previously in different studies that results between healhty people and people with type 2 diabetes can differ.

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I have a lot of time for charles brenner and think he is more often right than david sinclair, but this was not a valid criticism


What is not valid in the statement of the study?

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I’m very much confused about Metformin, especially after started taking 250 mg/day. Does it inhibit (C Brenner) or boosts (D Sinclair) mitochondria function?



“Charles Brenner, PhD, Chief Scientific Advisor - ChromaDex”

“Pioneering research on nicotinamide adenine dinucleotide (NAD+). Our Flagship Product TRU NIAGEN®”

“Dr. Brenner has made multiple seminal contributions to NAD+ metabolism,”

“Brenner, then a faculty member at Dartmouth College, discovered nicotinamide riboside (NR) to be a vital precursor of nicotinamide adenine dinucleotide (NAD+)”

Since Brenner is a competitor in the NAD+ field with Sinclair, I would take anything he says about Sinclair with a grain of salt.

I do not begrudge scientists and doctors trying to profit from their work, but once they associate themselves with a commercial product I quit paying much attention to them.


Peter Attia stopped taking metformin mainly because it inhibits the effects of exercise according to the tests he had done on himself but also according to some other studies. Today we don’t know if metformin works as good on healthy people as on people with type 2 diabetes.

Here are some studies that I have gathered throughout the years. Insulin sensitivity (2020, 2019, 2016, 2011), cardio fitness (2022, 2020, 2019, 2014, 2008), muscle growth (2019) and muscle strength (2021, 2019) will not be improved as much if metformin is combined with exercise instead of just exercising and not take metformin.

I know also Rhonda Patricks pushes on similiar things. But does this mean that we should not take metformin? I would say no but it’s good to have this in mind. If I also look at fasting which I practice. That also impacts exercise but it doesn’t mean that fasting is bad and something we should avoid.

Regarding the mitochondria function, metformin is a poison which impacts the mitochondria. A poison is not always bad. It’s about to find the right dose :pray:


Yes, I fully agree that it’s good to have Charles Brenners conflict of interest in mind. But he has a point that this study is done on people with type 2 diabetes and not on healthy people. I would be cautious about drawing big conclusions from this study on healthy people. We are not there yet but step by step forward :pray:

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All good points. Can we define “healthy people”? I would propose, at least in the U.S., about 50% of healthy people have insulin resistance. Also, is there a difference between absence of disease and being healthy? I appreciate the discussion! It may be that metformin is treating the disease of aging related to glucose / insulin dysregulation that does NOT meet our current parameters of disease state. Better monitoring and aggressive treatment with diet, fasting and exercise may erase much of the credit metformin gets credit for.


As I have previously posted, I have been taking metformin for decades based on the possible life extension benefits. Also, I stated that I didn’t notice any significant effect on muscle gain, strength, or endurance and posted my picture at age 81.

Once again I state IMO: The effect of metformin on exercise and muscle growth is overblown.

It appears that the effect of metformin on the mitochondria is beneficial, not harmful, though you may be right about the dosage being critical. Since huge studies of metformin in the past have not pointed out this undesired side effect of metformin, I must conclude at this point it is not significant.
If you know of any human trials that had this adverse effect on the mitochondria, please point them out.

This is a 2022 paper discussing metformin and mitochondria…

“Moreover, we discuss the potential benefits and future expectations of metformin by regulating the mechanism in mitochondria, and provide a new perspective for the current therapeutic application and future redevelopment of metformin.”


Uh source for metformin being a poison/causing damage? It slightly inhibits complex I but inhibition is not a poison and CR also slightly inhibits

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this should have been posted in the other thread

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Most people don’t have the energy, self-discipline, or fitness levels of Brad Stanfeld, Peter Attia, or Rhondra Patrick. Most Americans are sedentary. It’s probably a net-positive for most people


“I don’t like perky people”, Ed Asner

If I don’t remember it wrong als the results differs between people who are only insulin resistance and people how have type 2 diabetes so it’s not just that easy to look at if one is insulin resistance or not. But very good question about what is the definition of a healthy person. My quess is that the definition is little bit exclusive. A healthy person in this case is one without diabetes type 2 or insulin resistance. If you find anything in the topic let med know :pray:

Thanks for sharing your experiences :pray: One big problem is that most people are not exercising enough so if metformin has a small negative exercising effects then that can be good to take in consideration. If i’m not totally wrong Berberine and Acarbose has similiar effects as metformin but do you know if these have any negative effects on exercise? It was interesting that the latest ITP showed little bit better results on lifespan when Acarbose + Rapamycin was combined instead of Metformin + Rapamycin.

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The inhibition is not the poison part it’s how the inhibition on complex I is done.

“While endless pharmacovigilance has monitored the safety profile of metformin, its natural ancestor, G. officinalis (known as Professor Weed in the USA) is a Class A Federal Noxious Weed in 35 states of America, and appears on the database of poisonous plants.”

Take a look at compound guanidine. If you find anything that contradicts this let me know :pray:

The reason metformin is near the top of the list in anti-aging drugs is that new positive benefits for metformin keep popping up, such as autophagy and anti-inflammation.
I keep looking for new info. Here is an example of some research being done on metformin’s other benefits outside of blood glucose lowering.

“Metformin increased autophagy in CD4+ T cells from older subjects and shifted measures of mitochondrial bioenergetics and T cell inflammation to values indistinguishable from young subjects”


Yes, but this is problematic if people are not exercising enough. We have lots of statistics showing that muscle mass decreases when many people age. This has also made me rethink little bit fasting and especially extended fasting. If a person is not practicing efficient resistance training I would not recommend to practice extended fasting to often. All studies (more then 60 studies) both on humans and animals point that muscles are broken down during extended fasts. I haven’t found a single one study showing the opposite.

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