How Does Metformin Influence Longevity?

​Mankind has been on the lookout for centuries for the precious elixir of youth, but did it occur to anyone that it might have been laying all the time inside that 5 cent white pill, known as Metformin?
 
For long centuries, the active ingredient in metformin has been known and used for digestive health and treating urinary ailments. And since the beginning of the last century, it has been famous for treating diabetes due to its ingredients (guanidine) effects in lowering blood sugar and improving glucose metabolism. 
 
Yet after a century of using it among prediabetic and diabetic patients, substantial evidence shows that Metformin regulates cellular aging via its influence on inflammation, oxidative damage, diminished autophagy, and cell senescence; 4 fundamental pillars that can arguably extend lifespan in humans. And hey, all biohackers out there, behold the newborn wonder drug.
 
How does Metformin do it? It turns out that Metformin mimics the biochemical pathways set forth by intermittent fasting, inducing calorie restriction and more efficient sugar handling via insulin receptor sensitization.  A growing body of research supports the detrimental effects of accumulated glucose on aging proteins, a term now widely known as advanced glycation end products (AGEs).  The downstream effects of these include oxidative stress and its many manifestations, notwithstanding an inability to remove cellular debris, otherwise known as cellular senescence.  
 
A common factor among many age-related diseases such as diabetes, cardiovascular disease, dementia, and cancer, is a suppressed activity of the AMPK pathway.  And what is that? It is an essential enzyme, a master regulator for cellular energy homeostasis. To put it simply, it is responsible for mediating an effective solution to advanced glycation end product (AGE) damage, thereby lowering cellular stress, inflammation, and diminished autophagy. Several studies found that our good friend Metformin can increase the activation of the AMPK's pathway, thereby having a profound effect on the body’s ability to resist cellular damage caused by lifestyle, environment, and even the DNA that we were handed. 
 
With all the exciting data emerging about Metformin’s influence on longevity, caution should be held until more direct studies are done in non-diabetic patients. While many physicians will not block regulated, gradual doses of Metformin for non-diabetic patients, further human studies are needed to give a green light for broader safe usage of the drug.  Suffice to say, though, that this topic has never been more clinically relevant than in this era of health & wellness.  If a wide safety margin can be consistently demonstrated, then expect popularity to only explode with consumer awareness.