As metformin continues to make a tentative appearance in anti-aging research, scientists have been more than satisfied with the existing results. Not long ago, American scientist Professor Nir Barzilai was really ready to submit an application to the FDA to conduct a clinical trial to study the anti-aging effects of metformin. If approved, this would be the first clinical trial of an anti-aging drug in humans.
Metformin is the most widely used oral anti-diabetic drug in the world. It inhibits hepatic glycogen isogenesis while increasing insulin sensitivity in peripheral tissues to lower blood glucose and insulin concentrations. However, a growing number of studies in the last two years have found that metformin has anti-aging and life-extending effects.
Cell (March 28, 2013)
A study published March 28, 2013, in the journal Cell shows that metformin slows down the aging process by mimicking the effects of dieting. Researchers co-cultured nematodes with E. coli and subsequently tested the effects of metformin on these nematodes. They found that nematodes treated with metformin lived longer only when the co-cultured E. coli were sensitive to the drug.
The team used an E. coli strain that had defects in some genes related to metabolism, thus altering the level of available nutrients. With this the researchers figured out the metabolic signaling pathways that could be affected by the drug. They found that treatment with metformin disrupted the bacteria’s ability to metabolize folic acid (a B vitamin) and methionine (a protein building block). This restricted the nematode’s access to nutrients, mimicking the effects of dietary restriction and thus allowing the nematode to live longer.
Overall, the treatment with metformin lasted a total of six days, equivalent to about one-third of the nematode’s normal lifespan,” said Dr. Filipe Cabreiro, leader of the study and of the Institute of Healthy Aging at University College London. It appears to work by altering the metabolism of the bacteria that live in the nematode and instead restricting access to nutrients by the nematode host, thus obtaining effects similar to those of a restricted diet.”
Nature Communications (July 30, 2013)
A study published July 30, 2013, in Nature Communications shows that small doses of metformin given regularly at midlife promote health and extend the lifespan of mice, yet larger doses shorten their lifespan.
The team tested both 0.1 percent and 1 percent doses; the results showed that the mice taking the 0.1 percent dose survived nearly 6 percent longer compared to the group that did not take metformin. However, mice on the higher dose of metformin had an average lifespan reduction of more than 14% compared to mice not taking the drug, possibly due to renal failure. In contrast, lower doses of metformin did not appear to have any effect on the kidneys.
The study showed that metformin appeared to promote the use of fat for energy production in the mice, and that metformin also helped them maintain their body weight as they got older – a feature that other studies have found to be associated with longer survival. Mice taking metformin also had a lower incidence of cataracts. Cataracts were a common health problem in this mouse strain in the study. Metformin also prevented the onset of metabolic syndrome and appeared to exert some antioxidant effects in the mice.
Aging is a driving force behind metabolic syndrome and diabetes,” said Rafael de Cabo of the National Institute on Aging (NIA), the study’s leader. Given the clinical evidence that metformin alleviates the symptoms of these diseases and reduces the risk of cancer, we think it may be a good candidate to study its broader impact on health and longevity.”
PNAS (June 17, 2014)
In a study published June 17, 2014, in PNAS, researchers from Belgium found that metformin increases cellular robustness as well as lifespan by promoting the release of toxic oxygen molecules in cells, which could ultimately mitigate organismal aging and extend individual lifespan.
The researchers investigated the anti-aging mechanism of metformin in Cryptobacterium histolytica. As the body of Cryptobacterium histolytica ages, it slowly becomes smaller, wrinkles throughout the body and eventually becomes less motile, but the rate of body size reduction and wrinkling in nematodes treated with metformin decreased significantly, not only slowing down the aging rate but also restoring it to a healthy pattern.
Researcher Professor Wouter De Haes said that as the amount of harmful reactive oxygen molecules released from the cells decreases, it has a long-lasting beneficial effect on the cells, which normally use reactive oxygen particles efficiently before they become toxic to the cells. and prolong the life span of healthy cells.
Diabetes, Obesity and Metabolism (July 7, 2014)
In a study published July 7, 2014, in the journal Diabetes, Obesity and Metabolism, researchers at Cardiff University in the United Kingdom found that long-term use of metformin significantly extends the life span of people with type II diabetes, who are likely to live longer than non-diabetics, and that the drug also has health benefits for non-diabetics.
In the large-scale study involving 180,000 people, researchers studied the survival of type II diabetics taking metformin and those taking sulfonylurea, an oral drug used to treat diabetes, and compared the life expectancy of these patients to matched non-diabetics, with the same criteria for age, sex, whether they smoked and other clinical status indicators in the comparison population.
The results found that diabetic patients taking metformin had significantly improved individual quality of life compared with the same group of non-diabetic patients, and their life expectancy was even higher than the former, while those taking sulfonylurea had reduced quality of life and their life expectancy was lower than the same group of non-diabetic patients.
The researchers said that metformin, an inexpensive broad-spectrum anti-diabetic drug, would not only benefit people with type II diabetes, but would also have a beneficial effect on people with type II diabetes and even non-diabetics. Clegg Kerry, who led the study at Cardiff University, said. Professor Curry said: “Metformin has anti-cancer properties and may also help people fight off cardiovascular disease. The drug can also reduce the risk of diabetes in people at high risk of developing the disease by up to a third.”
Metformin anti-aging clinical trials may be initiated
As metformin continues to make its presence felt in anti-aging research, scientists have been more than satisfied with existing results. Not long ago, scientists at the Albert Einstein College of Medicine in New York, New York, U.S. Einstein College of Medicine scientists Nir Barzilai Professor really ready to submit an application to the FDA, hoping to carry out clinical trials to study the effect of metformin anti-aging.
It is reported that the FDA welcomed the proposal and considered the idea worthy of consideration. The study subjects will mainly include patients with cancer, heart disease and cognitive dysfunction, but not those who also have type 2 diabetes, because diabetics may have been able to take the drug and even if it works, it does not indicate a problem. These subjects will focus on testing for more disease and death in the future.
Nir Barzilai said the project plans to follow 3,000 people over the age of 70 for five years, and if the trial results are positive enough, the FDA will approve it. Currently, the main obstacle is the lack of funding, which requires $50 million. The research team is currently in discussions with several potential backers, including the National Institutes of Health.
Matt Kaeberlein of the University of Washington believes that Barzilai’s research program is sound. While other drugs have been found to have stronger anti-aging effects in animal trials, metformin’s long history of clinical use is an important foundation. If approved, this would be the first clinical trial of an anti-aging drug in humans.