Rapamycin for Anti-Aging in Dogs and Perhaps in Humans
The Goal of Anti-Aging Strategies
Rapamycin is a chemical produced by soil bacteria. In lab experiments, the chemical has significantly lengthened the lifespan of yeasts, worms, fruit flies, and mice. It's currently being tested in pet dogs. If this trial is successful, rapamycin may then be tested in humans. Rapamycin seems to work by inhibiting a protein known as mTOR.
The goal of anti-aging techniques varies. For some researchers, the main objective is to prolong life. For others, the aim is not so much to extend life but instead to ward off problems and diseases that are more common in old age. If these conditions are avoided or delayed, an individual should be able to remain healthy and active for a longer portion of their life. An added benefit is that avoiding certain diseases may lead to increased lifespan. Rapamycin could be useful because it appears to counteract some of the processes involved in aging.
Streptomyces: The Source of Rapamycin
Rapamycin is produced by a soil bacterium named Streptomyces hygroscopicus. The "Rapa" part of the drug's name comes from Rapa Nui, the original name for Easter Island. The chemical was discovered in soil collected from the island in 1965.
The suffix "mycin" is often used to name medicines made by species of Streptomyces. Many of these medicines have been discovered. They include antibiotics as well as immunosuppressive drugs. The genus Streptomyces is very useful for humans.
Not all antibiotics made by Streptomyces have "mycin" in their name. For example, chloramphenicol was found in Streptomyces venezuelae. It's an important antibiotic that is used to treat some serious diseases.
The Rapamycin Investigation
The mTOR protein was first described in 1991. At that time, it was of interest mainly because it was affected by rapamycin. Scientists have since discovered that it's a very important signaling molecule in cells and is involved in many processes, including (apparently) aging.
The Inhibition of mTOR and Immune System Suppression
Rapamycin is already used as an FDA-approved drug in humans. (The Food and Drug Administration, or FDA, is a federal agency that approves medicinal drug use in the United States.) The medicine is sometimes known as sirolimus or by the brand name of Rapamune. At high doses, it suppresses the activity of the immune system. This ability is very useful in preventing the body's rejection of tissue and organs transplanted from other people's bodies. The drug is frequently given to people who have undergone a kidney transplant.
Rapamycin is believed to inhibit the immune system by interfering with the action of T cells. T cells are a vital component of our immune system. The system protects us from invaders such as bacteria and viruses. Unfortunately, the body considers medically transplanted tissue from another person to be an invader, too, and attempts to destroy the tissue.
Once inside the body, rapamycin inhibits mTOR. The abbreviation "mTOR" stands for "Mechanistic Target of Rapomycin". The protein plays an important role in T cell activation and reproduction. When mTOR is prevented from doing its job, T cells are hindered and transplanted organs are safer.
Exploring the mTOR Pathway: David Sabatini's Research
Rapamycin as a Cancer Treatment
Rapamycin can fight at least some types of cancer via its action on mTOR. The mTOR protein stimulates the growth and reproduction of other cells besides T cells. It's often mutated (changed) in cancer cells. This mutation leads to increased reproduction of the cells. Since rapamycin inhibits mTOR, it can be helpful in stopping cancer cell reproduction and in treating the disease. The "hyperactive" mTOR in some types of cancer seems to be especially sensitive to the presence of rapamycin.
There are two versions of mTOR—mTORC1 and mTORC2. mTORC1 is the version involved in most research and is the type that seems to be most closely related to cancer development.
Enzymes are a type of protein. mTOR is an enzyme that acts as a kinase. Kinases are enzymes that transfer phosphate groups from high-energy molecules to other substances. MTORC1 is sometimes referred to as a master growth regulator. It promotes both the growth of cells and their proliferation.
Rapamycin and Life Extension in Mice
Multiple experiments have shown that rapamycin increases the lifespan of mice by about 20%, depending on the conditions of the experiment. The chemical is exciting because its anti-aging benefit has been shown in different studies performed by different people. This indicates that the claim that it lengthens the life of mice is very likely true.
At the moment, it's unknown how rapamycin increases the lifespan of yeasts and lab animals. There are several theories, but they haven't been proven. It's thought that the inhibition of mTOR is somehow involved in the process.
Rapamycin is a bioactive chemical. A bioactive substance is a non-nutrient chemical that produces an effect (or effects) inside the human body.
How Does Rapamycin Fight Aging?
There are two leading theories for rapamycin's method of action, as described below. The chemical may extend life in more than one way.
Reducing the Amount of Protein Synthesis
One way in which mTOR triggers activity and growth in cells is by stimulating the process of protein synthesis. It's suspected that the buildup of misfolded proteins in our body is one cause of aging. It's been suggested that by reducing the number of proteins that are made, rapamycin also reduces the number of misfolded proteins produced as well as the resources needed in the attempt to repair them. This may be part of the answer to the anti-aging puzzle, but the evidence doesn't support it in all cases.
mTOR is involved in a chain of chemical reactions that inhibits autophagy. Autophagy is the breakdown of organelles and proteins in cells. Inhibiting this process is useful under normal circumstances, but autophagy has some benefits. The breakdown of damaged structures and the recycling of their components for new construction can be helpful for a cell. Autophagy is also helpful when a cell isn't receiving enough nutrients.
Rapamycin inhibits mTOR and promotes autophagy. Various researchers have observed that promoting autophagy can have rejuvenating and life extension benefits for yeasts, worms, flies, and mice, so this may be one way in which rapamycin reduces aging. The worm used in life extension research is usually Caenorhabditis elegans, often known as C. elegans. The fly is frequently Drosophila melanogaster, or the fruit fly.
Rapamycin may also extend life by inhibiting cancer and reducing inflammation. The immune system launches an inflammatory response to attack invaders. This inflammation is normally temporary. Increased and chronic inflammation is believed to be a contributor to the aging process.
Aging in Dogs
The research into the effects of rapamycin on dog aging is being performed by scientists at the University of Washington. They call their research the Dog Aging Project. The researchers suspect that the drug may increase the lifespan of dogs by two to five years.
I wouldn't allow my dog to be treated with rapamycin at the moment due to the uncertainty about its effects. I certainly understand the attraction of the drug for dog owners, though. Dogs have such short lives compared to ours. They are intelligent animals that make wonderful companions and often become much loved members of the family. Sadly, their lifespan is only around twelve to fifteen years, although some dogs die at a younger or older age. It's heartbreaking for a dog lover to say goodbye to multiple dogs as the person goes through life.
A small number of interventions have been shown to reproducibly and robustly extend lifespan in mice. Among these, the best candidate for working similarly in dogs and people is a drug called rapamycin.— The Dog Aging Project at the University of Washington
The Dog Aging Project at the University of Washington
Researchers at the University of Washington are carrying out two studies in their Dog Aging Project. One is called the "Longitudinal Study of Aging in Pet Dogs". This is a nationwide study of dogs throughout their life. The goal is to discover why some dogs succumb to diseases such as cancer, dementia, and kidney failure in old age while others don't.
The second study is called the "Rapamycin Intervention Trial in Pet Dogs". There are two phases in this study. The first involved a small group of pet dogs living in Seattle. All were older than six and were middle-aged. They were given a low dose of rapamycin for ten weeks. During this time, their blood chemistry, heart function, and microbiome was monitored by veterinarians. The "microbiome" is the community of predominantly helpful bacteria and other microscopic organisms that lives in the gut of dogs and humans.
The second phase in the rapamycin intervention trial is still in progress. It involves dogs from a wider area and is a long-term project. Its goal is to discover the effects of rapamycin on lifespan and health. The dogs will be monitored closely and frequent tests will be performed to assess aspects of their health.
The goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence aging. We want to use that information to help dogs and people increase healthspan, the period of life spent free from disease.— The Dog Aging Project Website
Dog Safety and Side Effects of Rapamycin Treatment
At the high doses used to treat kidney transplants and cancer, there may be major side effects of rapamycin treatment in humans. These include increasing the risk of diabetes, hindering wound healing, and suppressing the immune system in cases where this isn't desirable. Only a low dose of the drug is needed to extend the lifespan of mice, however. The potential side effects of rapamycin use as well as the potential anti-aging benefits are of great interest to researchers.
The risk of side effects from a medicinal rapamycin treatment is probably acceptable for someone with a life threatening disorder. It may not be acceptable for relatively healthy people. The University of Washington researchers say that the anti-aging doses of rapamycin used in mouse experiments have caused few to no side effects in the mice, however. They suspect that the low doses of the drug used in their dog aging project will cause no significant problems, either.
About 70% of dogs that took the highest dose of the drug were also noticeably more active.— Time Magazine (with reference to the first phase of the Rapamycin Intervention Trial)
Benefits of Anti-Aging Research in Pet Dogs
The Dog Aging Project may have important benefits for both dogs and humans. It would be wonderful if our pets had an increased lifespan while remaining healthy. Using dogs in the research instead of mice and simpler animals could be beneficial for humans beyond giving us a longer time with our pets, however.
Confirmation of rapamycin's effects in dogs is likely to take several years. Although dogs live for a short time compared to humans, they live much longer than the mice and other animals tested in lab experiments. The wait for the research results may be very worthwhile, though. Dogs are more similar to humans with respect to physiology and behaviour. Discoveries in dogs may therefore be more applicable to humans than those already made in lab animals. Another advantage of dog research is that results will be obtained more quickly than the equivalent research in humans due to the shorter lifespan of dogs.
At the moment, it's unknown whether rapamycin has anti-aging benefits in humans. If it does and if it's widely used, problems may arise. Most people would probably consider living for longer a great idea, as long as they stayed healthy and reasonably happy. If life extension strategies become routine, however, we may experience overpopulation and changes to the structure of society.
Potential Benefits of Understanding mTOR
The research at the University of Washington is personally interesting to me. Sam (the dog in my first photo) died of cancer, which is unfortunately common in golden retrievers. Cancer in dogs is a topic that is being investigated in the Longitudinal Study of Aging at the university. Misha is in the second half of his life now and has a greyer face than in the photo above. Increasing his lifespan with rapamycin or another substance, or at least maintaining his health as he ages, would be wonderful. Dylan is still young, but like all dogs he will live for a much shorter time than most humans.
Hopefully the anti-aging potential of rapamycin will be very successful in dogs. If not, we should have at least learned more about mTOR. It's a fascinating chemical and its effects appear to be far-reaching. We know more about mTORC1 than mTORC2 at the moment. Both seem to be very important. Our research and knowledge of the substances could help us in many other ways besides extending lifespan.
- Rapamycin information from the Journals of Gerontology and Oxford Academic
- Information about sirolimus use as an immunosuppressant from the Mayo Clinic
- Rapamycin treatment for a type of pancreatic cancer from the National Cancer Institute
- Less TOR protein extends mouse lifespan from the NIH (National Institutes of Health)
- Hyperactive mTOR mutations and rapamycin from the NIH
- The Dog Aging Project website
- A report about the dog aging project from Time magazine
Questions & Answers
© 2015 Linda Crampton