The Fountain of Youth dates back to the time of the Greeks and then to the Spanish conquistadors who searched the Caribbean for the mythical place where the water of life would reverse aging. These days our search has turned inward, where we look for chemical or cellular pathways to stop or reverse cell aging or loss. One such study was just published that focused on reducing the natural loss of stem cells as we age. As a physician, perhaps the most exciting thing about the research is that it used an already existing medication that was discovered in bacteria on Easter Island. Let me explain.
When the cells in your body become damaged, they are replaced by local stem cells that live in that tissue. For example, if a cartilage cell in the knee is dying, a stem or progenitor cell that lives next door will detect it and begin the steps to replace the sick cell. This is called differentiation. How does this work?
First, an adult stem cell nearby gets wind of a chemical signal released by the dying cell. The stem cell then makes two copies of itself; one cell will be kept in reserve for future use (replacing the stem cell being used for the repair job), and the other cell will replace the dying cell (this is called a progenitor cell). The progenitor cell receives many local clues from the surrounding cells, including the type of forces present (compression, stretching, sliding, etc.), the chemicals in the environment (inflammatory, pro-growth, status quo, etc.), and the cell type that surrounds it. Those signals transform the progenitor cells into the exact cell type that needs to be replaced. When the repair job is complete, remember that we still have one stem cell in reserve. This cell then goes into wait-and-see mode, waiting to spring into action at a future date when more damage is detected. Watch the video below to see visuals of this process.
When this fine balance between cell death or damage and differentiation is disrupted, problems can ensue. Unfortunately, even just the natural process of aging causes stem cells to die off and decreases their ability to regenerate damaged tissues. And one of those keys to the process of aging is found in the mTOR pathway…
Mammalian target of rapamycin (mTOR) is quite a mouthful, but what you need to understand is that mTOR is a large protein that promotes and regulates the growth of cells, and it is a key pathway to the process of aging. Problems with the mTOR pathway have been associated with a variety of diseases, including diabetes and genetic disorders, and it is extensively studied in seeking treatments for cancer. The new study also suggests that repeated, or chronic, activation of that mTOR pathway as we age may be responsible for stem cell loss.
Rapamycin is now an immunosuppressant drug, which means it prevents the immune system from doing its job. While Ponce de León was searching for the water of life in Bimini, rapamycin was being produced by bacteria on Easter Island (halfway across the world)! In fact, the compound, which was discovered in a 1972 expedition, was named after the native name of the island, which was Rapa Nui. So maybe all of those big statues were trying to tell us something!
Why would we want to inhibit the immune system? Rapamycin is commonly prescribed following organ transplants, for example, so the immune system doesn’t target the donor organ as a foreign invader and attack it. Autoimmune conditions, such as Hashimoto’s thyroiditis and rheumatoid arthritis, are other examples where immune suppression might be beneficial depending on the severity. Rapamycin is also sometimes used, more controversially, on drug-eluting stents, which are devices that support a vessel that has been dilated to improve blood flow.
Now the new study suggests that rapamycin may not only prevent but also reverse stem cell loss caused by the mTOR pathway as we age. Let’s review.
The new study consisted of mice (flies were also used) that were the human equivalent of 50 years old or older, all of which had experienced a decline in stem cell counts. The mice were treated with the drug rapamycin, and in all cases, the stem cell counts recovered. Researchers determined the rapamycin reversed the loss of stem cells in the aging mice (specifically in the muscle and trachea, as well as in the intestines of the flies). How? They concluded that the prevention of stem cell loss can be accomplished by inhibiting or blocking the repeated activation of mTOR signaling that occurs with age or injury, and rapamycin treatment was the vehicle that accomplished this.
No, you shouldn’t be taking rapamycin to protect stem cells or slow aging. Despite the promising findings in the study, this doesn’t mean we should all rush out and get prescriptions for rapamycin. While this study may be the first of more to come to attempt to find additional solutions for stem cell loss in humans as we age, rapamycin is riddled with side effects that would likely negate its benefit to stem cells. Most of us, for example, wouldn’t want the harmful effects that would go along with blocking our immune system from doing its job.
The upshot? What’s really fascinating about this study is that it involves an existing drug. Also that it may be possible to find other ways to inhibit the mTOR pathway that are nontoxic and have fewer side effects. While Ponce de León, the Spanish governor of Puerto Rico, was searching the Caribbean for the Fountain of Youth, turns out it may have actually been located where all of those giant statues guarded the shore of an obscure island in Polynesia!
About the Author
Christopher J. Centeno, M.D. is an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. He is board certified in physical medicine as well as rehabilitation and in pain management through The American Board of Physical Medicine and Rehabilitation.…