Metformin: Is It an Effective Anti-Aging Drug?

Metformin is a drug that has been used to treat type 2 diabetes. However, more recent research has shown that it may also have potential as an anti-aging drug. Let's explore the effects of metformin and the controversy surrounding its life extension possibilities.

How does metformin work?

Metformin is a drug that has been used to treat type 2 diabetes. It belongs to a class of drugs called biguanides which work by decreasing liver glucose production and increasing insulin sensitivity in the muscle and fat tissues. More recently, metformin has shown potential as an anti-aging agent that may be able to extend lifespan and improve health in old age.

Taking metformin results in lower glucose levels in the blood and improved glucose control in people with type 2 diabetes. It has been used along with lifestyle changes such as diet and exercise to treat diabetes for over 50 years. However, its precise molecular mechanisms are still unknown.

While metformin has been approved by the U.S. Food and Drug Administration (FDA) to treat type 2 diabetes since 1995, it is also used off-label to treat polycystic ovary syndrome (PCOS). Research in humans and animals suggests that metformin may have other cardiovascular and neuroprotective effects. It has been shown to improve health outcomes and extend life in organisms such as yeast, worms, and mice.

Does Metformin have anti-aging benefits?

Metformin exhibits anti-inflammatory properties in both cells and subjects, even those who do not have diabetes. Since inflammation is a contributor to cardiovascular disease, Alzheimer's disease, and cancer, researchers hypothesize that metformin may extend lifespan and improve quality of life by helping to prevent these age-related diseases in the first place. There is also evidence that metformin helps modulate the human microbiome, but the precise mechanisms are still unknown.

However, one review suggests that in addition to metformin's anti-inflammatory and microbiome effects, it has been proposed to target all the hallmarks of aging and their interconnectivity, including the following:

• Improving nutrient-sensing
• Enhancing autophagy
• Boosting intercellular communication
• protecting against macromolecular damage
• Delaying stem-cell aging
• Modulating mitochondrial function
• Regulating transcription
• Lowering telomere attrition and senescence

While people do take metformin prophylactically as an anti-aging and longevity drug, this is done off-label. Researchers continue to study the effects of metformin on lifespan and quality of life, as well as specific age-related concerns like skin, hair, and eye health, energy levels, and cognitive decline in the event that the drug can be used in patients without type 2 diabetes.

Metformin's ability to slow aging depends on how aging is defined. Some people are looking to add more years to their lives, while others want to look and feel younger longer. It's unclear if metformin can help do either in non-diabetics, but it may be able to improve wellness in some ways.

Metformin's effect on skin and hair

Skin and hair rejuvenation is the much-desired effect of anti-aging treatments. However, there is little formal evidence for the role of metformin in reversing skin damage or hair loss in healthy people. It's more likely that metformin's ability to treat some aging-related diseases, cardiovascular diseases, skeletal diseases, and neurodegenerative diseases creates the conditions for better hair and skin.

There is ongoing research into whether topical metformin or metformin tablets can induce hair growth. In a study of women with PCOS, taking metformin decreased the incidence of hair loss. A recent study has also shown that metformin can induce hair regeneration in mouse cells. However, the precise causal mechanisms remain unclear, and there is minimal evidence that metformin causes hair growth in healthy people.

Multiple studies have shown that metformin has an anti-inflammatory effect that can help relieve some inflammatory skin disorders, such as psoriasis, acne, and allergic contact dermatitis. However, the results are based on either human studies in people with comorbidities (diabetes, metabolic syndrome, and obesity) or on mice. Meaning that while metformin has been shown to benefit patients with psoriasis and comorbidities, there is no clear evidence supporting its use in patients with psoriasis but without comorbidities.

Topical administration of metformin has also been shown to have a beneficial effect on wound healing and the regeneration of mechanically stretched skin. Researchers hypothesize that it may play a role in collagen synthesis based on the mice studies, the formation of new blood vessels (angiogenesis), and skin-derived stem cell proliferation. This could be used as a topical anti-aging skin agent, but more research is required.

Metformin and improved eyesight

Metformin can improve eyesight in those with diabetic retinopathy. It has also been shown to reduce the incidence and effects of uveitis and macular degeneration in those with type 2 diabetes. Studies gauging the effectiveness of metformin for age-related macular degeneration in healthy people as ongoing, but it appears to be effective in mice. People taking metformin for anti-aging have provided some anecdotal evidence for improved eyesight.

Can metformin boost metabolism and cellular function?

It is hypothesized that metformin promotes the reduction of body fat, in part, by improving insulin resistance and endothelial function in the vasculature. It may also boost mitochondrial function (increasing the efficiency of energy production in your mitochondria). However, even if metformin boosts these functions, many other factors play a role in energy, metabolism, weight loss, and overall aging.

A series of studies in humans and mice have also shown that metformin increases the level of the peptide hormone growth/differentiation factor 15 (GDF15) circulating in the body, which can help boost energy and lower body weight. In diabetes patients, metformin can result in modest weight loss by acting as an appetite suppressant. Since obesity is a leading factor in the progression of age-related diseases, metformin-related weight loss could help extend a person's life expectancy and quality of life. However, weight loss in non-diabetics may be negligible.

Can metformin slow aging?

Metformin may be able to improve a person's health span — the period of life spent in good health. However, research is still underway to discover any possible connection between anti-aging or life extension and metformin in people without diabetes.

Some researchers have reviewed decades of literature and found the anti-aging benefits of metformin to be controversial, particularly in patients who are not currently suffering from a disease. Other researchers have lauded metformin's cardio protective effects, suggested it can prevent some forms of cancer, and proposed its use in preventing age-related diseases and promoting longevity.

Metformin as an anti-cancer agent

Since type 2 diabetes can increase the risk of some cancers, the use of metformin has been explored as an adjunctive cancer therapy. Metformin may be able to help treat some cancers by suppressing oxidative stress and reducing glucose uptake, both of which play a role in promoting tumor growth. It's typically combined with chemotherapy or radiation.

Studies have also shown that the drug can inhibit the formation of new blood vessels in tumors, which in turn can decrease the growth and spread of cancer cells. However, researchers are still exploring appropriate doses of metformin for cancer treatment, the possibility of relapse after combined therapies, and whether metformin is effective in non-diabetic cancer patients.

The National Cancer Institute is currently funding several human trials to determine if metformin may play a role in preventing or treating breast cancer, endometrial cancer, chronic lymphocytic leukemia, and smoldering multiple myeloma.

What are the side effects of metformin?

Below you will find a list of common, less common, and rare side effects of metformin.

Metformin vs other anti-aging supplements: which is better?

While aging was declared a “disease” by the World Health Organization in 2018, there are no FDA-approved treatments for it. However, there is growing interest in the use of drugs and supplements to reduce the effects of aging. These include:

Rapamycin

Rapamycin is an immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR), which plays a role in everything from regulating insulin and metabolism to assisting brain, muscle, and tissue function.

Dysregulated mTOR has been implicated in diseases like obesity, diabetes, cancers, autism spectrum disorders, Alzheimer's disease, lupus, and lymphoproliferative diseases, as well as shortened lifespans (in fruit flies, some worms, and yeast). That is why rapamycin's ability to inhibit mTOR is linked to preventing and treating these same conditions.

Nicotinamide mononucleotide (NMN)

NMN is NAD+ precursor. NMN supplements might be a miracle cure for aging.

These supplements may become in various forms: powders, and various types of pills (regular and liposomal). Also, there are some types of foods that contain NMN, so you can boost your NAD+ levels naturally.

NMN supplements can be changed with Nicotinamide Riboside (NR) when it comes to slowing age-related disease and degeneration.

NAD+

NAD+ is crucial to proper cellular function, but decreases as we age. As we already covered, NMN is an NAD+ precursor, but NMN supplements are banned in the US.

Researchers have hypothesized that taking an NAD+ supplement could help fend off age-related disease and degeneration, but research is ongoing. These supplements may be better than taking NAD+ when it comes to slowing age-related disease and degeneration.

Senolytics

Senolytics, such as Dasatinib, are repurposed anti-cancer drugs that can selectively kill harmful cells in the body. Other examples, such as Quercetin, and Fisetin can also be naturally found in many foods. Cell senescence is linked to an improvement in cardio metabolic disorders, inflammatory conditions, neurodegenerative diseases, and cancer, but this research is limited to mice.

Urolithin A (UA)

Urolithin A is a microbiome metabolite of dietary ellagic acid, a polyphenol found in numerous fruits and vegetables such as pomegranate. Researchers have hypothesized that UA can increase mitochondrial function and reduce excessive inflammation in models, and could someday benefit both aging and elderly people.

What is the dosage of metformin for anti-aging benefits?

Metformin's anti-aging dosage is unknown. However, the maximum safe dose of metformin for people with diabetes is typically 2,000–2,500 mg per day. Since metformin is only approved to treat type 2 diabetes, there are evidence-backed guidelines on how to take metformin for longevity.

However, one study of metformin for longevity used a dose of 1,600–1,700 mg/day following the model of the Diabetes Prevention Program. While metformin can be prescribed at dosages of up to 2,250 mg/day, no further effects of decreasing glucose are noted after 1,600–1,700 mg/day.