Metformin is the hot drug among anti-aging researchers. In man's eternal and titanic fight against the passage of time, this drug seems to be the one indicated by experts in antiaging medicine as the most promising molecule to delay aging and, therefore, also postpone the appearance of age-related diseases. such as cardiovascular diseases, dementia or certain types of cancer.
The metformin molecule comes from a plant quite common in Europe and the Middle East, Galega officinalis. This plant has been used for centuries to treat multiple ailments, including one of the common symptoms of diabetes, frequent urination, when this metabolic disease had not even been described yet. Today and for several decades, in fact, metformin is the drug of first choice for the treatment of diabetes.
And it was precisely a study led by Bannister CA with patients with this disease that in 2014 put the spotlight on this drug in the field of anti-aging medicine. In that study, researchers at Cardiff University (United Kingdom) compared the life expectancy of apparently healthy people without diabetes with that of patients with type 2 diabetes who progressed to first-line monotherapy treatment with metformin or sulfonylurea. The result? Patients taking metformin had a life expectancy that was 38% higher than that of patients taking sulfonylurea and 15% higher than that of people without diabetes.
“On the list of possible drugs with an anti-aging effect, metformin is undoubtedly one of the highest right now; but you have to be patient and keep in mind that these patients have a metabolic disorder, so treating that metabolic disorder can already have an anti-aging effect in itself. But, for a person who has a good metabolism, what happens if you change their metabolism with metformin? Well, we don't know: it may work, nothing happens, or it may have a negative effect," reflects Dr. Salvador Macip, professor at the Open University of Catalonia (UOC) and the University of Leicester (United Kingdom), where he directs a cancer and aging research laboratory.
That same “but” was what researchers from the Department of Public Health at the University of Southern Denmark put on the table, who in 2022 tried to replicate Bannister's study without success. According to the authors of the Danish study, Bannister's control group was made up of people who were not taking metformin or who were not diagnosed with diabetes, which did not mean that they were necessarily healthy people, which would explain to some extent the differences found in the Life expectancy.
By the time these “buts” arrived, however, the enthusiasm around metformin had already given rise to hundreds of new investigations, some of which linked use of the drug to a lower incidence of cancer, a lower risk of developing dementia and a reduction in mortality from all causes and the incidence of diseases of aging.
“We have already demonstrated and published in observational studies that metformin is good for cardiovascular prevention, for dementia, for some types of cancer; And in animal models, an increase in life expectancy has also been seen. So what is clear is that metformin does something in the healthy human subject, that it produces those other effects that are not directly subject to a prescription aimed at controlling diabetes,” argues Dr. Ángel Durántez, one of the leading experts. international in the field of anti-aging medicine.
Recently, in addition, a group of researchers from the Clínica Universidad de Navarra (CUN) has started a research project in which more than 15 Spanish hospitals participate and which aims to analyze the impact of metformin in patients with COPD, one of the main pathologies associated with accelerated aging. The researchers, led by Dr. Juan Pablo de Torres, co-director of the Department of Pulmonology at CUN, aim to slow down the accelerated loss of lung function—one of the clinical representations of accelerated aging—in patients with COPD. Also analyze the impact of the drug on the development of major cardiovascular events, tumors of any type—especially lung cancer—and kidney disorders.
“The novelty of this study, what makes it so innovative, is that no one had considered intervening in early aging in such a prevalent disease, since around 12% of the adult population in Spain has COPD. If we manage to confirm this theory with our findings, the potential that this has on patients is very important, especially considering that we are talking about a very cheap and safe medicine,” Torres explains to La Vanguardia.
The fact that it is a cheap medicine, precisely, is the upside and downside for metformin. The face, because if its anti-aging effects are confirmed, we would be talking about a drug accessible to the vast majority of the population. The cross because its low price and the fact that it is a drug not subject to patent reduces the interest of the pharmaceutical industry in research, since there is no promise of a great economic return.
The prestigious researcher Nir Barzilai, professor of medicine and genetics at the Albert Einstein College of Medicine, is precisely encountering this wall, who has been trying to raise funds for several years to launch an already approved clinical trial, Targeting Aging with Metformin ( TAME). It is a work that aims to demonstrate reliably that metformin can modulate aging and its diseases beyond an isolated impact on diabetes, something that would pave the way for the development of next-generation drugs aimed directly at the biology of aging.
But what is the mechanism of action that makes metformin a potential anti-aging drug? In the article A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Improves Healthspan and Extends Lifespan, published in the scientific journal Frontiers Endocrinology, its authors point out several plausible possibilities. Among them, metformin activates the production of sirtuins, proteins that reduce oxidative stress in cells and promote DNA repair. Or that the drug activates the AMPK pathway, a metabolic pathway that is linked to longevity, while, on the contrary, it inhibits the mTOR pathway, another metabolic pathway that is negatively related to longevity.
“The AMPK pathway is a key regulator of many cellular pathways that are related to both health and lifespan, including the benefits of calorie restriction. Therefore, as an AMPK activator, metformin has come under the microscope as a potential anti-aging drug and its potential role in that regard has been promoted. “It is noteworthy that sensitivity to AMPK decreases with age, promoting the argument that AMPK activators, such as metformin, could delay aging,” argue the authors of the review.
For Dr. Ángel Durántez, who is quite satisfied with the conclusions of the review, the impact of metformin on aging may ultimately have less to do with the inhibition of metabolic pathways linked to obesity or with the production of sirtuins, as with another aspect that is put on the table in the scientific review: the optimization of glucose metabolism. “We know that this is one of the pillars of aging, that if you improve hydrocarbon metabolism, you will really have a global impact on morbidity and mortality and, therefore, you will be acting on longevity,” says the expert.
Durántez points out that the hydrocarbon metabolism is precisely one of the health factors that is least controlled by today's society due to the large amount of processed and ultra-processed foods consumed and the tendency to consume hyper-sugar foods such as carbonated drinks. “When you do analysis, you realize that even for those people who believe they take good care of themselves, it is not easy to have the markers of hydrocarbon metabolism (basal glucose, basal insulin, glycated hemoglobin, etc.) at optimal values. That is my criterion for prescribing metformin. Do not make a blind prescription for the impact it will supposedly have on longevity, because we still do not know; but rather a prescription aimed at improving the values of hydrocarbon metabolism, which are a basic pillar of aging,” he reflects.
These values, Durántez recognizes, can also be controlled with a healthy life. That is, taking care of your diet and rest, having an active life and reducing the intake of toxic substances (alcohol and tobacco) to a minimum. In fact, in the Frontiers Endocrinology review, its authors did not hesitate to express their concern about the possibility that the use of metformin as a prophylactic to delay aging could serve to reduce the incentive to seek the proven benefits of lifestyle changes. of life. “Metformin should not be viewed as a “quick fix” panacea for aging at the expense of non-pharmacological interventions such as diet, exercise, and related lifestyle changes,” they noted in their writing.
Starting from this basis, however, Dr. Ángel Durántez highlights the importance of research such as TAME finally going forward to corroborate all the alleged benefits of metformin, especially in a context like the current one, marked by the aging of the population. worldwide and the exponential increase in the incidence of chronic non-communicable diseases. “Being late to these diseases is unsustainable, so the search for anti-aging drugs is something that will have to be addressed sooner or later. And no, it is not a question of the frivolity of the billionaire who wants to live longer. Here we are talking about extending life in health and well-being, which is imperative. If we get confused thinking that this is a frivolity of the rich, we are in trouble,” he concludes.
