If you have diabetes or know someone who does, you’ve probably heard of metformin. It’s a common medication used to treat and prevent type 2 diabetes (T2DM). Recently, studies have shown that metformin’s benefits go beyond just controlling blood sugar. It also helps with aging by promoting cell repair and reducing inflammation and oxidative stress. These positive effects, seen in both people with T2DM and animals like worms and mice, have led researchers to ask: could metformin also be an anti-aging drug?
Metformin’s Botanical Origins
Before it became the medication we know today, metformin came from the French lilac plant. In medieval Europe, this plant was used to treat diabetes-like symptoms, such as frequent urination.
In 1918, scientists found that guanidine, an active ingredient in the plant, could lower blood sugar in animals. However, guanidine was too toxic for long-term use. By the 1920s, safer synthetic versions called biguanides were developed, and metformin was one of the first. It was approved for treating diabetes in the 1950s in Great Britain and France, named Glucophage, meaning “glucose eater.”
In the U.S., the FDA approved metformin in 1995 after other biguanides were taken off the market due to a rare but serious side effect, lactic acidosis. Today, metformin is the most prescribed oral drug for T2DM worldwide, with over 150 million users. In the U.S., it’s the third most prescribed medication.
Metformin stands out because it doesn’t cause hypoglycemia, a dangerous drop in blood sugar. It’s also beneficial for conditions like polycystic ovary syndrome (PCOS), gestational diabetes, obesity, and prediabetes. Affordable, accessible, and well-tolerated, metformin is known for its safety. Common side effects are mild, usually involving some stomach discomfort, which often goes away after a week or two. It’s considered an essential medicine by the World Health Organization. But how did it become seen as a potential promoter of longevity?
Metformin in the Context of Aging
Aging affects all species. While aging mechanisms vary, there are common cellular pathways involved in the aging process. Early studies in other organisms showed that metformin could positively impact health and lifespan by affecting these pathways.
Research has extended beyond animal models. The UKPDS (U.K. Prospective Diabetes Study), which followed over 5,000 diabetic patients for 20 years, found that metformin significantly reduced the risk of heart attacks and death by a third in overweight patients with T2DM. This study showed that improving glucose and blood pressure control could prevent or delay T2DM complications.
A 2014 study by Bannister et al. looked at 180,000 people in three groups: diabetics taking metformin, diabetics taking another medication (sulfonylurea), and non-diabetic individuals not on any medication. The surprising result was that diabetics on metformin not only outlived those on sulfonylurea but also lived longer than healthy non-diabetics. This finding suggests that metformin may have anti-aging effects beyond just lowering blood sugar.
Simplified Rewrite:
In addition to being great at lowering blood sugar, metformin also helps with various conditions like HIV complications, PCOS, autoimmune diseases, and cognitive decline.
The most exciting area of research is metformin’s potential in cancer prevention and treatment. There’s a lot of evidence that metformin can protect against several types of cancer, such as colon, prostate, breast, and lung cancers, and it can even slow down tumor growth. Currently, there are thirty ongoing trials looking into metformin’s effects on different cancers.
How Metformin Affects Aging
Aging is the biggest risk factor for diseases like cancer, diabetes, heart disease, and neurodegenerative disorders like Alzheimer’s and Parkinson’s. These diseases become 100 to 1000 times more likely between the ages of 35 and 85 due to the gradual build-up of cellular damage over time.
Metformin’s effects on blood sugar are well-known. It lowers blood sugar by reducing glucose production in the liver, decreasing glucose absorption from the gut, and improving the body’s response to insulin. It also helps with weight loss by making you feel fuller.
Scientists have recently discovered how metformin works at the cellular level, affecting key pathways linked to aging.
How Does Metformin Work?
When metformin enters a cell, it interacts with complex 1 (MC1) in the mitochondria, the cell’s power plants. This makes the cell think it has less energy, triggering several beneficial processes:
AMPK Activation: AMPK is an enzyme that helps the cell use energy efficiently. It’s activated when energy is low, like during fasting or exercise. Metformin boosts AMPK, which helps with weight control and clears out damaged cells. It also improves insulin sensitivity and lowers blood sugar levels.
Autophagy Activation: Autophagy is the cell’s recycling system, breaking down and reusing cellular waste. This process helps prevent cancer and protects the brain from diseases like Alzheimer’s by removing toxic proteins.
mTOR Inhibition: mTOR is a growth switch in cells. While it promotes cell growth, if it’s on for too long, it can lead to cancer. Metformin uses AMPK to block mTOR, preventing uncontrolled cell growth and reducing the risk of cancer and inflammation.
Decreased IGF-1 Signaling: IGF-1 is a hormone that promotes growth. As we age, we need less growth and more protection against breakdown. Metformin blocks IGF-1, helping cells use insulin more efficiently and lowering blood sugar levels.
Reduced ROS Production: ROS are harmful molecules that can cause cell damage. Metformin helps control ROS levels, improving DNA repair, metabolic function, and reducing chronic inflammation.
Preventing Senescence: Senescent cells are damaged cells that stop growing but release harmful substances. Metformin helps clear out these cells, preventing tissue and organ degeneration.
Inflammation Reduction: Chronic inflammation damages cells and tissues over time. Metformin reduces inflammation, protecting against various age-related diseases.
TAME – Targeting Aging with Metformin
Researchers are conducting a large clinical trial called TAME (Targeting Aging with Metformin) to see if metformin can delay multiple age-related diseases. Led by Dr. Nir Barzilai, this study will enroll 3,000 non-diabetic participants aged 65-79 and measure metformin’s effects on health outcomes like cognitive function and disease incidence.
The TAME trial aims to prove that aging can be treated as a medical condition, opening doors for more research and innovation in aging. Inspired by centenarians who live longer and healthier lives, the trial hopes to show that aging can be improved with metformin.
Conclusion
Metformin, primarily known for managing diabetes, has the potential to impact aging and longevity positively. By addressing multiple aging pathways, metformin offers hope for extending life span and preventing age-related diseases. The ongoing TAME trial will provide valuable insights into metformin’s role in aging, potentially redefining how we age and live healthier lives in our later years.
