Rapamycin: Benefits & Side Effects
Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
Rapamycin is a drug occasionally prescribed off-label for increasing longevity.
This drug interacts with the mTOR pathway, which can stimulate cells to use alternate energy pathways in a way similar to fasting.
Taking a natural supplement like fatty15 can help you support your cellular health and activate longevity enhancing pathways.
You may have already heard about rapamcyin, arguably the leading longevity-enhancing molecule. Although rapamycin is a promising candidate, it is a prescription drug, which limits access and the studies needed to confirm its benefits on longevity.
Let’s learn about the science behind its longevity enhancing benefits and how a newly discovered as essential saturated fatty acid also has longevity enhancing benefits with the bonus of being a safe and easy to take.
What Is Rapamycin?
Rapamycin is an immunosuppressant medication initially intended to be used by organ transplant patients. The drug was given to them so that their immune systems wouldn’t attack the organs they had just been given. It was officially approved by the FDA for this use in 1999 and is currently sold under the brand name Rapamune (aka sirolimus).
Where Did Rapamycin Come From?
Rapamycin was discovered in 1972 from bacteria found on Easter Island, aka Rap Nui (which is why it has its given name). It was thought to be helpful because the people living in the region did not develop certain diseases that they presumably should have developed due to their surroundings.
The compound was left in a lab in Montreal for years until the early 2000s when it was “rediscovered” by a researcher looking for useful compounds. It was shown to extend lives in clinical trials of worms and yeast. Between 2009 and 2016, it was tested on mice. The mouse model also showed that it had life-preserving effects.
How Does It Relate to Human Longevity?
It may extend the lifespan of worms, yeast, and mice, but what can it do for humans? The link lies in a discovery made by Dr. David Sabatini. While researching as a student, Dr. Sabatini discovered a new protein in mammals called the mammalian target of rapamycin, or “mTOR.”
MTOR is a protein that regulates certain functions inside our cells, like cell proliferation, autophagy (the process by which our cells use old, worn-out cell parts for fuel), and apoptosis (cellular death) by engaging in numerous signaling pathways in the body.
This is important because these are some of the functions that underlie the aging process. Scientists identified 12 phenomena in our cells that are directly associated with aging.
The so-called “12 hallmarks of aging” include:
Weakened cellular communication. Our cells need to be able to communicate with each other to ensure proper homeostasis among important cellular functions (like glucose uptake).
Genomic instability. Biological and chemical changes in our environment can change how our cells proliferate. This is most commonly observed in cancer cells and is associated with aging.
Telomere attrition. Our chromosomes are protected on the ends by telomeres, but with age, telomeres become shorter, and a portion of vital DNA is lost in this process.
Epigenetic alterations. This refers to alterations made by our own activities and lifestyle (like our diets, exercise patterns, sleep habits, etc.).
Loss of proteostasis. Proteostasis refers to the pathways cells use to create vital proteins. The pathway involves the synthesis of the protein to degradation.
Deregulated nutrient sensing. Cells need to recognize and effectively use the nutrients we ingest. Over time, our cells lose the ability to recognize how much of which nutrients are needed.
Mitochondrial dysfunction. The batteries of our cells lose their power as we age. Mitochondrial function begins to decline, and the mitochondria produce less ATP (energy) and more reactive oxygen species (ROS).
Cellular senescence. As cells age and lose their function, they should reach a state of apoptosis or cell death. This is a normal part of the cell cycle. However, with age, our cells stop working before their programmed death. This is called cellular senescence and occurs when these cells do not die but instead remain in the body, creating inflammation and an atmosphere of toxicity.
Stem cell exhaustion. Stem cells can morph into whatever type of cell the body currently needs. However, with age, stem cells lose their function, too.
Disabled macroautophagy. Autophagy is the body's process of reusing damaged cell parts. Autophagy declines with age, and this reduction plays a role in physiological aging and age-associated disorders.
Chronic inflammation. Higher levels of pro-inflammatory markers are often seen in aging adults and can predict the risk of cardiovascular diseases, frailty, and physical and cognitive function decline.
Dysbiosis. Dysbiosis is a significant change in gut microbiota. A microflora imbalance can cause several diseases and can contribute to aging. The slower intestinal motility of aging can result in changes in nutrient exchange and microbiota composition.
Combined, these nine cellular phenomena cause us to develop age-related diseases and to age in general. Since mTOR plays a role in some of these functions, ensuring that mTOR function is balanced is crucial for healthy cells.
How Does mTOR Work?
MTOR forms two specific complexes (known as mTOR complex 1 or “mTORC1” and mTOR complex 2 or “mTORC2”).
- MTORC1 is involved with cell growth factors, nutrient uptake, and cell energy supply. This compound mostly involves cell growth.
- mTORC2 plays a role in cell proliferation (creating new cells) and survival.
MTOR is involved heavily with our nutrient-sensing pathway, which means it can target and modulate one of the ways that the cells age (deregulated nutrient sensing).
Rapamycin’s Mechanism of Action
So, how does rapamycin play a role in mTOR signaling? Rapamycin targets mTOR and provides health benefits similar to fasting.
Caloric restriction causes mTOR to turn off, forcing cells to find alternate means of food, like autophagy. That means the cells will seek out dysfunctioning organelles and ingest them as food, helping clear away damage.
Bottom line: Rapamycin helps protect cells from nutrient deregulation and also helps stimulate the process of autophagy.
Who Can Take Rapamycin?
Currently, rapamycin treatment is only approved by the FDA for transplant patients. You shouldn’t take rapamycin unless it has been prescribed to you by your primary health care provider.
While some websites claim to offer rapamycin, you should only trust rapamycin prescribed by your doctor from your pharmacy. That said, it isn’t unheard of for a doctor to prescribe rapamycin for off-label use.
However, it’s important to remember that long-term use of rapamycin is still being studied. We don’t yet fully understand the long-term side effects of using rapamycin for extended periods of time.
Side Effects of Rapamycin
Because rapamycin is an immunosuppressant, you are more susceptible to becoming ill. The FDA requires a black box label for rapamycin warning against this side effect. An immunosuppressant medication suppresses immune function, which could cause you to get sick more frequently.
Some patients taking rapamycin develop skin infections, while others may develop serious or life-threatening illnesses, like pneumonia. Right now, rapamycin simply is not intended for long-term use.
As we further study it, we can evaluate whether or not it is beneficial for longevity. In the meantime, there are other ways we can support our cells and protect against the hallmarks of aging.
Safe Cellular Support
We care for our bodies with a healthy diet, plenty of exercise, good stress management techniques, and ensuring we get the sleep we need. Most of us, however, don’t take measures that directly support our cellular health and target the hallmarks of aging. One molecule has recently gained attention as a potential natural longevity enhancing molecule is C15:0.
C15:0 or pentadecanoic acid was discovered as a potential longevity candidate by Dr. Stephanie Venn-Watson, who was working to improve the health, wellness and longevity of dolphins. To learn more about her discovery and how C15:0 improves dolphin and human health, watch her TED talk here.
How C15:0 Works
C15:0 strengthens weak cells and rescues them from dysfunction by:
- Creating stronger cell membranes. Cell membranes wear out with age. When they become weak, cells can lose shape, interfering with cellular function. They are also less protected. C15:0 is a sturdy fatty acid that integrates into cell membranes, improving cellular strength by 80 percent.
- Clearing damaged cells. C15:0 activates a protein called AMPK, which effectively clears away damaged cells. AMPK also plays a role in glucose and immune regulation.
- Regulating inflammatory response. We all know inflammation (especially chronic inflammation) is dangerous inside the body. C15:0 significantly calms and lowers proinflammatory cytokines, a molecule directly linked to aging.
- Restoring mitochondrial function. Your mitochondria need a wake-up call, and C15:0 delivers, rescuing energy-generating pathways and restoring cellular ATP levels by up to 350 percent. C15:0 also decreases the amount of reactive oxygen species produced by cells by up to 45 percent.
- Activating PPARɑ and PPARẟ receptors. These important receptors help regulate functions like sleep, mood, and even appetite. C15:0 interacts with these receptors, helping establish balance and regularity.
Further, numerous peer-reviewed studies have shown that people with higher C15:0 levels have better metabolic, heart, immune and liver health. Unfortunately, our C15:0 levels naturally decline as we age, so how can we best get C15:0 back into our diets?
How To Get C15:0
C15:0 is found primarily in whole-fat dairy products (whole milk and full-fat butter), however increasing your intake of whole dairy also means increasing the ‘bad’ even-chain saturated fats and increasing caloric intake.
Further, studies looking at whole fat dairy consumption have been inconsistent, some showing benefit and some showing negative effects on our health and wellness
A solution? Fatty15.
Fatty15: The C15:0 Supplement Your Cells Need
You can skip the cows and added calories and get just the good fat by taking fatty15 each day. Fatty15 is the first and only supplement born from scientific research that contains just one simple ingredient: the pure, vegan-friendly, sustainably-produced, award-winning, version of C15:0 called FA15TM.
Just one capsule per day is all you need to increase your circulating level of C15:0 and level up your battle against zombie cells (among other highly researched cellular and overall health benefits).
Fatty for Life
Fatty15 is your key to improving your cellular health and targeting the hallmarks of aging with a safe, easy to take, once a day supplement . We might one day be able to use rapamycin for similar goals, but for now, we can rely on the research we have about C15:0 to support our cells and help us live healthier, longer. Age on your own terms with fatty15.
Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems | PLOS ONE
Eric Venn-Watson M.D.
Senior Scientist, Co-Founder
Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.
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