• Metformin prevents brain atrophy, elevating cognitive function in aged male primates
• Metformin slows the pace of aging across diverse male primate tissues
• Metformin counterparts neuronal aging, delivering geroprotection via Nrf2 in male primates
Summary
In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin’s influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin’s effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.
A small amount of additional detail is available in this Nature news brief. Details on design, method, and often unavoidable procedural imperfections are not found in these summaries. I was unable to get full access. In principle, this is a very good study. I was troubled only by some of the “marketing”-like language but that may be a translational issue. The brain aged more slowly in monkeys given a cheap diabetes drug.
Well, there is this tidbit in the news brief: " This led Guanghui Liu, a biologist who studies ageing at the Chinese Academy of Sciences in Beijing, and his colleagues to test the drug on 12 elderly male cynomolgus macaques (Macaca fasciucularis ); another 16 elderly monkeys and 18 young or middle-aged animals served as a control group. Every day, treated monkeys received the standard dose of metformin that is used to control diabetes in humans. The animals took the drug for 40 months, which is equivalent to about 13 years for humans."
Correct! I was just able to get access thru my institution:
" Monkeys were fed three meals and had free access to water. Along with breakfast, the O-Met group was treated every day with 20 mg/kg metformin administered through drinking water over the duration of the study (40 months). "
Remember that this is a Chinese study, so a good 50% of the papers out of China are fake. We have many Western studies on Metformin and longevity, and unless you have diabetes or taking Rapamycin, it doesn’t really make sense to take it. I’d disregard this study until we have more compelling evidence.
The brain aged more slowly in monkeys given a cheap diabetes drug
Daily dose of the common medication metformin preserved cognition and delayed decline of some tissues.
A low-cost diabetes drug slows ageing in male monkeys and is particularly effective at delaying the effects of ageing on the brain, finds a small study that tracked the animals for more than three years1. The results raise the possibility that the widely used medication, metformin, could one day be used to postpone ageing in humans.
Monkeys that received metformin daily showed slower age-associated brain decline than did those not given the drug. Furthermore, their neuronal activity resembled that of monkeys about six years younger (equivalent to around 18 human years) and the animals had enhanced cognition and preserved liver function.
This study, published in Cell on 12 September, helps to suggest that, although dying is inevitable, “ageing, the way we know it, is not”, says Nir Barzilai, a geroscientist at the Albert Einstein College of Medicine in New York City, who was not involved in the study.
But did Nir Barzilai actually have anything to do with this study, or are the authors quoting him to give the article merit? It looks like the latter to me, and that makes me more suspicious of the findings.
(However, I do take Metformin with my Rapamycin so I am hoping the article is true. Yet, I am skeptical.)
Just saying china and then judging is not the optimal way to engage with data
At a high level perhaps at least ask
what country AND:
what institution/city (This paper would rank higher on that metric)
what journal (this is arguably one of the worlds top 2 scientific journals…)
And then, given that (2) and (3) look good, it’s probably worth looking at the paper and its data and methods + see what other top scientists seems to think about it
I am already following the paper’s recommendations, so, as I stated earlier, I hope it is correct.
I’m afraid I have to disagree with #2. I live in China, and although the institution that wrote this paper is in Beijing, it still doesn’t instill confidence in me. It’s a Chinese mentality issue and this issue has been getting much worse recently as the government slides further into dictatorship. When people are scared for their jobs or freedom (or life) they’ll produce results needed to keep their job or freedom.
This gives a good idea of the current environment in China.
Here in Hong Kong, a new precedent has been set this year. A protestor was convicted for 10 years. The lawyer defending him also received the same sentence for defending someone who was obviously criminal. That is the China of 2024.
Using the FDA conversion guide, the human equivalent dose of 20 mg/kg in cynomolgus monkeys is 6.4 mg/kg (20 x 0.32). So, about 500 mg/day for most adults (but only 384 mg for a 60 kg human, for instance). My concern about metformin has always been medium and high doses (>= 1 g/day), and I wondered whether low-dose could be beneficial. This article strengthens the case for low-dose metformin. (It would be good to have something like 250 mg ER on the market.)
However, Eric Topol wrote the opposite: did he make a mistake?
Given that the dose is low, could it just be that many of these monkeys (if not the majority) had diabetes, prediabetes, or just suboptimal glycemic control, and metformin fixed that?
You are creating a straw man and not addressing what I am saying
Help me understand what you don’t agree with
There is a lot of crappy research and even fraud and false data being published
This happens everywhere, but even more for instance China than most western countries
We should in general be skeptical of results of a single paper that are not reproduced or at least well triangulated with other known data and publications
Item (2) means that one should on average be more suspicious about a Chinese paper vs a US paper
But while China might be producing among the most false papers in the world, they also have been making massive investments in the science sector of their civilization and an increasing % of the world’s scientific insights and scientific successes are coming from China - partially just do the shear size of their scientific community and the amount of investment going into the sector
So the goal should not be to throw the baby out with the bath water, but to try and capture the stuff that actually is good
Some ways to look at that is to look at where the paper was published, what the track record of the authors and the the institution has been in the past
I agree with 1-4. I disagree with 5 on. When 50% of a country’s papers are garbage, I’ll need supporting evidence from another trusted source before I even consider it.
Remember that Dr. Sinclair is from Harvard, the most trusted university in the world. Yet, I don’t trust the Resveratrol research.
