Metformin as an anti-aging therapy
Metformin is the most prescribed drug for the treatment of diabetes or prediabetes. However, sometimes new applications of some drugs are discovered in what is called "off-label" use, which can lead to the approval of new therapeutic use. In the case of metformin, its anti-aging properties are being unveiled.
Off-label drug use occurs when the drug is used for a therapeutic purpose that is not approved by regulatory agencies (such as the FDA). This type of use may be inadvisable because it has not been sufficiently tested in clinical trials, and therefore its efficacy and side effects have not been rigorously verified.
However, in recent years there have been many examples of new applications of traditional drugs, discovered from research studies or from clinical practice. These processes can eventually lead to what is called repositioning or repurposing of the drug when it goes through the regulatory approval process for use.
An example would be zidovudine, better known as AZT, which was developed in the 1960s for the treatment of cancer, without success, and twenty years later was one of the first treatments available for HIV patients. Or sildenafil, which was initially developed for hypertension, and which later found use in erectile dysfunction, such as the well-known Viagra.
Metformin is the most prescribed drug for the treatment of diabetes but its anti-aging properties are being unveiled.
Interest in the use of metformin as an anti-aging agent stems from animal models, in which it has been shown that those treated with the drug increased their longevity. In humans, indications that metformin may prolong life come from observational studies in which diabetics treated with metformin were found to have better survival rates even compared to non-diabetic control individuals. A meta-analysis found that metformin reduced total mortality rates and cancer incidence compared to non-diabetics not treated with metformin. Lower rates of cardiovascular disease were also found than in diabetics treated with other therapies.
Metformin seems to affect energy production in the mitochondria of our cells, which may also be related to its geroprotective effects.
The mechanisms by which metformin acts as an anti-aging agent are not entirely clear.
On the one hand, one mechanism in which metformin appears to act is another cellular pathway called mTORC1. Calorie restriction and some drugs such as rapamycin have shown that inhibiting the activation of mTORC1 can prolong life in animal models. Metformin also acts in this way, which may also contribute to its effects on longevity.
Metformin could also activate sirtuins, a pathway also related to the anti-aging effects of calorie restriction, or drugs such as nicotinamide riboside.