Funny the things one remembers. Like “Don’s Fountain of Youth,” a short cartoon I saw some time back in the 60s. “Don” was Donald Duck and the story was all about taking his nephews on a Florida vacation. The “kids” are more interested in reading comics than the sights that Donald is pointing out, at least until they chance upon a pond with a sign "Mistaken for the Fountain of Youth by Ponce de Leon 1512." Donald decides to have a little fun with his nephews and removes the “mistaken for” part of the sign. He wades into the water and pretends to have turned into an egg that he found in a nearby nest.
I was intrigued by that cartoon for a couple of reasons. I was sort of a history buff and wondered whether the reference to Ponce de Leon was real or fictional. And the “Fountain of Youth” caught my attention because I had grown up with a special fondness for perhaps the most famous Hungarian musical, “Janos Vitez” (John the Valiant) based on a poem by the celebrated poet Sandor Petofi in which the “Spring of Life,” capable of conferring immortality plays a vital role.
Checking the Encyclopaedia Britannica in those pre-Google days revealed that Ponce de Leon was indeed a real Spanish explorer who gave Florida its name upon seeing a landscape filled with flowers. Stories about his search for a Fountain of Youth, however, did not emerge until after his death and appear to be mythical. But tales of waters that restore youth have been with us for thousands of years. Alexander the Great supposedly looked for a restorative spring and a famous 1546 painting by Lucas Cranach the Elder depicts aging people entering a pool on one side and emerging as youths on the other.
These days, the search for the fountain of youth is more likely to lead us to a bottle than a spring or lake. There are waters that are oxygenated, hydrogenated, alkalized, ionized, clustered, frequency harmonized, catalyst altered, photonically enhanced, plasma activated, vibrationally charged, chi energized, or DNA encoded. Their ads flood us with scientific-sounding lingo and promises of health and rejuvenation. But the science is all wet and drips with crackpot notions. If a fountain of youth is to be found, it may indeed be found in a bottle, but it won’t be filled with “penta,” “double helix” or “negative field activated” water. It will likely contain a pharmaceutical product of some sort. Maybe something like metformin.
Metformin is the most widely used diabetes drug in the world. It decreases glucose production in the liver, increases insulin sensitivity and enhances the uptake of glucose from the bloodstream by cells. All of this amounts to reducing the amount of glucose in the blood, the hallmark of diabetes control. But why the connection to aging? Because a universal sign of aging is the development of insulin resistance, a condition in which cells progressively fail to respond to insulin, the cell’s gatekeeper for the entry of glucose. As insulin resistance develops, blood levels of glucose rise and diabetes eventually sets in. Since diabetics are at an increased risk for cancer, heart disease and inflammatory conditions, it comes as no surprise that metformin has been associated with a decreased risk of these ailments. Given that such illnesses are normally age related, researchers began to wonder whether aging was actually a sort of prediabetic condition that could be retarded with the appropriate use of metformin.
When scientists are confronted by such a premise, they tend to turn to mice. Mice may not be men, but they can be given known doses of a drug, their diet can be controlled, and their health status and life span can be readily determined. When researchers at the National Institutes of Health in the U.S. treated mice with metformin at a dose of 0.1% by weight of their total food intake, the animals’ mean life span was extended by about 6%! Interestingly, even though the treated mice had consumed more calories, they weighed less than the controls, likely because of an increased use of fat for energy. Confirming the notion that the difference between a drug’s ability to cure or to kill lies in the dose, a tenfold increase in the amount of metformin given resulted in a 14% shorter lifespan.
The mechanism by which this drug extends life isn’t clear but some clues are emerging from research with Caenorhabditis elegans, a tiny worm that is commonly used to study aging because it has a lifespan of only three weeks. Also, their aging process can be followed visually because the little creatures get smaller, wrinkle up and move more slowly. That is, unless they are treated with metformin. Then they lead longer, healthier lives. And it seems that effect has to do with metformin’s ability to generate a small dose of reactive oxygen species (ROS). These are generally a normal product of metabolism but because of their “free radical” character are highly reactive and can cause cellular damage. Indeed such “oxidative stress” has been associated with aging and theories abound about the use of antioxidants to counter the process. But now Belgian researchers have cast a shadow on this widely accepted theory by demonstrating that metformin produces a small dose of ROS that actually increases the robustness and longevity of a cell. If this effect can be confirmed, it would imply that antioxidants could actually negate the benefits of metformin.
Of course we are neither mice nor worms, so we will have to wait for more evidence about metformin’s benefits before jumping on the anti-aging bandwagon. Many wagons carrying the likes of human growth hormone, dehydroepiandrosterone (DHEA), shark cartilage extracts and megavitamin supplements have ground to a halt after a promising start. Metformin, however, may yet hatch into an effective life extension treatment. But let me take you back to Donald for a moment. The egg he picked up to trick his nephews into believing in the anti-aging effect of the Fountain of Youth turned out to be an alligator egg. And that resulted in an unforeseen outcome, namely Donald being chased by a pretty angry alligator mom. That chase, though, had a real antiaging effect. Exercise really does turn back the clock. Just look at Donald, he hasn’t aged a bit. He turned 85 in 2019.
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