Since the beginning of time, people have desired to live longer, to extend their time on earth as long as possible. In modern times the concept of “healthspan” as opposed to simply “lifespan” has been used to clarify the values of truly extending our time in good health. To extend our healthspan and lifespan we need to decrease the period of morbidity associated with aging at the end of life. This is often referred to as “squaring the curve.”
The Effect of Cellular Aging or “Zombie Cells”
In recent decades, the rapidly expanding knowledge of biochemistry has pushed the longevity discussion into the molecular knowledge of senescence. Senescence is when a cell ages and permanently stops dividing but does not die. Popularly referred to as “zombie cells” they float around in the body wreaking havoc on the normal organ functions. We can easily picture these cells on the surface of our skin as dead skin causing deep wrinkles while the healthy base layer of skin never gets a chance to come to the surface.
Unfortunately, this process is happening throughout our bodies as we age, slowly damaging every organ system by clogging it up with old cells that refuse to die and an aging immune system that doesn’t target them for death effectively. These effectively dead cells are not benign (harmless). They excrete inflammatory cytokines, growth factors, and proteases that inhibit the normal function of the surrounding cells and cause inflammation. This process has been directly linked to many inflammatory diseases including osteoarthritis, aging skin, atherosclerosis, and kidney disease among others. Rapamycin may play a major role in supporting our immune system in ridding our bodies of these zombie cells.
What is Rapamycin?
Rapamycin was originally identified in soil bacterium on Easter Island, also known as “Rapa Nui”, thus it was named “Rapa-mycin.” This compound was found to have powerful anti-fungal properties. When it was brought back to the lab it was also found to modulate the action of immune cells. Unfortunately, it was then labeled as an “immunosuppressive” agent. As research has exploded around Rapamycin it behaves clearly as more of an immunomodulator, helping the immune system target these senescent cells that need to be cleared out for organ systems to function better.
Rapamycin and Longevity
Rapamycin targets immune cells by acting on a cell protein known as mTOR (Mammalian target of rapamycin). This protein complex was discovered only after the discovery of Rapamycin and thus was named mTOR but more recently the mechanistic target of rapamycin as it is found in many other species beyond mammals. The mTOR pathway plays a central role in cell metabolism of many tissues in the body including liver, muscle, adipose (fat) tissue, the brain and many cancers. Excessive activation of mTOR plays a critical role in the development of type 2 diabetes (via increasing insulin resistance), increases cancer growth, increases inflammation, and increases fat deposition. However, since continually or permanently suppressing mTOR is found to significantly suppress cell proliferation/growth it was labeled as an “immunosuppressive” drug and in the subsequent decades since FDA approval in 1999 it has been used primarily in solid organ transplant patients.  
Research and interest in Rapamycin has exploded since 2000 when it was found that rapamycin significantly extended the lifespan of worms, yeast, flies, and mice. There are thousands of completed and ongoing studies on Rapamycin and other “rapaloges” that target mTOR in the treatment of a wide range of diseases.
As research and understanding of mTOR has developed it became clear that taking Rapamycin in a pulsatile fashion (weekly or every few days) instead of daily, exerted different effects on cell metabolism. Studies on longevity use this pulsatile approach and the studies that have been done thus far in animal models (particularly in mouse models) have been very successful. Additionally, studies combining metformin and rapamycin have been even more impressive, increasing lifespan up to 23% in mice.
The Safety, Risks, and Benefits of Rapamycin
If you are interested in considering this medication, we highly recommend reading as many of the links/footnotes on this page as possible to educate yourself about longevity research and rapamycin. Rapamycin Longevity News keeps up-to-date research on Rapamycin conveniently in one location as well as patient feedback on the medications.
Due to the use in immunosuppressed patients with organ transplants, Rapamycin has carried many warnings that may not be accurate when used as an isolated agent in low doses on healthy patients. As a result of this history however, it is still important to monitor white blood cell counts and Rapamycin levels every three months. The use of Rapamycin for longevity is considered completely off-label and is not approved by the FDA.
It is critically important if you are considering this medication to read about the risks and benefits. Although the risks appear to be trivial (especially when taken in a pulsatile fashion as suggested by longevity experts), they are worth noting. In pulsatile doses used for anti aging there are few reported side effects.
Typical Rapamycin Dosing
Most people taking Rapamycin take it as a once-weekly dose, as permanent mTOR suppression is not desirable. Low-doses are used most frequently, although research into the optimal dosing and timing is ongoing. Medication prices range widely, and unfortunately have been increasing. Rapamycin is rarely covered by insurance outside of the organ transplant setting.
What to Expect with Rapamycin Treatment
During an initial visit, we take a thorough health history, answer any questions you may have about Rapamycin, and check the following initial fasting labs:
- CBC (Complete Blood Count)
- CMP (Comprehensive Metabolic Panel)
- Lipid Panel
- Hemoglobin A1C
- Uric acid
- Three month repeat labs (including Rapamycin/sirolimus levels) and a visit
Many studies are ongoing for addressing Rapamycin as an adjunctive treatment for a variety of cancers, and research into use of Rapamycin for autoimmune diseases has been completed or is ongoing.
Recommended reading: Rapamycin for Longevity: Opinion article, by Mikhail Blagosklonny, MD, Phd.
Interested in learning more about optimizing your health with Rapamycin? Contact us: 303-884-7557.
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969078/ “Does longer lifespan mean longer healthspan?” Trends Cell Biol. 2016 Aug; 26(8): 565–568.
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690269/ “The compression of Morbidity”
 https://www.nature.com/articles/550448a “To stay young kill the zombie cells”
 mTOR: a pharmacologic target for autophagy regulation – PMC (nih.gov)
 What is rapamycin? | New Scientist
 The Dirty Drug and the Ice Cream Tub | Radiolab | WNYC Studios (Excellent podcast of the history of Rapamycin)
 Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells (∗) – Journal of Biological Chemistry (jbc.org)
 Mammalian Target of Rapamycin – PMC (nih.gov)
 Curcumin inhibits the mammalian target of rapamycin‐mediated signaling pathways in cancer cells – Beevers – 2006 – International Journal of Cancer – Wiley Online Library
 The mechanistic Target of Rapamycin: The grand conducTOR of metabolism and aging – PMC (nih.gov)
 Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer – PMC (nih.gov)
 Drug Approval Package: Rapamune (Sirolimus) NDA# 021083 (fda.gov)
 RAPAMYCIN (AY-22, 989), A NEW ANTIFUNGAL ANTIBIOTIC (jst.go.jp)
 The Combination of Metformin and Rapamycin Increases Lifespan by 23% – New Life Longevity
 (PDF) mTOR inhibition improves immune function in the elderly (researchgate.net)
 Pharmacokenetics and Safety of a Single Dose of Rapamycin (sirolimus) in Healthy Males firstname.lastname@example.org