Metformin: Is This Old Diabetes Drug an Anti-Aging Blockbuster?

All drugs currently used in the arsenal to treat type 2 diabetes have as a singular goal, reduction in the level of glucose (sugar) in the blood. One of the oldest drugs in this arsenal is metformin, which was originally sold with the trade names such as Glucophage and Glumetza, but has been available as a generic for many years. Metformin has been used to treat diabetes for nearly 60 years so its use is associated with a vast patient base and has a demonstrated low level of toxicity. Metformin is a drug that belongs to the class of drugs called biguanides.

Although metformin is prescribed as a treatment for type 2 diabetes, and as such is effective through its modulation of various metabolic processes, over the 60 odd years of its use numerous other potentially important functions have been elucidated. I wrote about the emerging potential for the use of metformin as an anti-aging drug nearly 4 years ago so it should be clear this is not a new observation:

METFORMIN: IS THIS DIABETIC DRUG AIDING LIFE SPAN BY MEANS OTHER THAN JUST GLYCEMIC CONTROL?

So I felt it was time to look at this story once again to review all the ways this old drug might be acting to reduce the cellular effects of aging. In a general sense aging at the level of the whole body is nothing more than the global summation of the effects of aging at the cellular level. When cells age they lose the ability to adequately respond to the accumulating effects of aging so that the process exerts a snowball rolling downhill effect, the problems get bigger and bigger. Humans cannot survive without oxygen but oxygen is also highly toxic and over time the ability of cells to repair the damaging effects of oxygen become reduced. Oxygen is not the only contributor to the overall aging process but it is a major contributor. The body, and the cells that make up the body, are constantly exposed to ionizing radiation, to radiation in the form of sunlight, and to toxic chemical compounds in our environment, the food we eat and the water we drink. Over time cells loses the ability to keep up with the constant onslaught.

So how does metformin fit into the potential arsenal of anti-aging agents? Major cellular processes that contribute to aging are inflammation, loss of natural stress defenses (oxygen oxidizing DNA, RNA, and proteins are forms of cellular stress), and defects in the process whereby cells normally recognize and remove damaged proteins and cellular constituents. The latter constitutes a process called autophagy (literally "self eating"). Metformin exerts numerous effects that put these processes back on track, thereby, reducing the effects of cellular aging. Go to my website if you want to review the details of the processes of autophagy:

http://themedicalbiochemistrypage.org/cell-turnover.php#autophagy

Metformin activates a powerful enzyme in cells that is considered the master metabolic regulatory enzyme. This enzyme is called AMP-activated protein kinase (AMPK) and as the name kinase implies adds phosphate to its plethora of substrates. AMP (adenosine monophosphate) represents the depleted form of cellular energy (ATP; adenosine trisphophate) and by activating AMPK induces cells to switch from metabolic pathways that consume energy to those that yield energy. AMPK also phosphorylates and inhibits the major protein complex (called mTORC1, which if you care to understand you can by going to the link above) that exerts a negative (inhibitory) effect on the process of autophagy. If autophagy is inhibited then damaged (oxidized for example) proteins and other cellular components cannot be degraded and their constituent parts reused by the cell so the cell tends toward the consequences of aging and eventually cell death. So as a consequence of metformin autophagy is less inhibited and cells can undergo a higher level of autophagy and thereby reduce the potential for age-related cell death. Metformin also regulates inflammatory process by inhibiting the activity of a protein called NF-kB (nuclear factor kappa B). NF-kB is a transcription factor (regulator of gene expression) that is one of the most potent immune system activators. Thus, by inhibiting this transcription factor metformin can reduce the level of inflammation which can reduce the impact of inflammation at the cellular level and the enhancement in aging processes associated with chronic inflammation.

So what is the TAKE HOME message here: Metformin is available ONLY by  prescription so don't go out to your local dietary supplement store expecting to find it on the shelf. However, it is likely that in a very short period of time there may be over the counter medications that mimic the anti-aging effects of metformin that may indeed slow down the process of cellular aging and, therefore, serve as longevity promoting medicines.

So what if anything can one do now? There are several plant derived supplements that have been shown to activate the same enzyme, AMPK in cells in culture or in laboratory animals that are being promoted as anti-aging longevity inducing supplements. Some of these potential anti-aging supplements/compounds are resveratrol, curcumin, and berberine. You can read up on many of these supplements on my website:

http://supplementscience.org/anti-aging.html

But buyer BEWARE, although cell culture experiments have associated some of the supplements with anti-aging properties through activation of AMPK, there is little, if any, hard core double-blinded clinical study evidence proving that these supplements work as touted by their sellers. For example, berberine definitely activates AMPK in cell culture but its absorption from the human intestinal system and its distribution throughout the body in a bioactive state is essentially ZERO and although resveratrol in red wine is absorbed relatively well most resveratrol supplements do not show effective uptake from the intestines nor bioavailable distribution throughout the body!!! Thus, one would be advised, at least by me, to wait for further experiments to develop more readily absorbed and distributed formulations. 

While you are waiting drink some green tea and make a vegetable dish flavored generously with turmeric!!!

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