The Rapamycin “Story”

Rapamycin is the most successful life extension drug ever discovered. Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome is a book that presents two main topics. The first is the story of rapamycin, which is the most effective life extension drug ever discovered. The second topic is a discussion of mTOR and autophagy, which are counter-regulatory mechanisms that regulate metabolism, health and the aging process in all living cells. These topics have led to a new understanding of how we can effectively slow down the onset of age-related diseases.

Rapamycin was discovered in soil samples taken during a scientific expedition to Easter Island in 1964. Soil samples from that expedition contained a compound that was produced by a strain of soil bacteria named Streptomyces rapamycinicus. This compound was given the name rapamycin because Rapa Nui is the name the indigenous people called their island. Ultimately, rapamycin was patented by Wyeth (now Pfizer) under the brand name Rapamune ® with the generic name of sirolimus. FDA Approvals: Early testing revealed that rapamycin exhibits immunosuppressive activity.In September 1999, rapamycin received FDA approval as a drug to prevent organ rejection in patients receiving a kidney transplant.1 Rapamycin and its analogs (rapalogs) also exhibit anti-proliferative properties. Two rapalogs, temsirolimus and everolimus have received FDA approval to treat various forms of cancer in 2007 and 2009 respectively. 2,3

Since receiving FDA approval, rapamycin has been taken safely by millions of patients with no unexpected problems.

Rapamycin’s Mechanism of Action

mTOR is a protein in cells that senses the availability of nutrients. In 1994, David Sabatini isolated and identified this protein, which is now referred to as the mechanistic target of rapamycin (mTOR) 4. When rapamycin enters cells, it binds to mTOR and inhibits the activity of this key signaling compound in cells.

mTOR’s Function

When nutrients are available, TOR initiates signals that activate cellular metabolism, telling cells to utilize the available nutrients to build new proteins, enzymes, and other cellular components. mTOR activates cellular anabolic (building) processes of growth and proliferation. The discovery of mTOR has resulted in new understanding of cellular metabolism, health and the aging process. Now, 25 years after its discovery, over 11,000 papers have been published on mTOR.

Autophagy: The Ultimate Detox

Autophagy is a process within all cells that counterbalances mTOR’s activities. When mTOR is not activated (when nutrients are not available), autophagy is switched on.

Autophagy is the process in which damaged proteins, enzymes, and other older cellular components are selectively broken down for reuse or elimination. Terms that describe autophagy’s function include cellular renewal, revitalization, recycling and detoxification.

The mTOR/Autophagy Ratio

Humans have been evolving on earth for 2-3 million years. Throughout 99.9% of mankind’s evolution, people had to hunt or forage for their food every day. Our hunter-gatherer ancestors did not eat 3 meals a day and their bodies were well-adapted to periods of not eating.

In the last one hundred years, advances in agriculture, refrigeration and food packaging and preservation have played a major role in changing how much people eat, and how often people eat. These changes have made food easily available for most people all the time.

mTOR Syndrome 

Today, food is easily available 24/7. Consequently, modern humans spend far more time consuming and digesting food each day compared to our ancient ancestors. Consequently, many modern humans spend about 16 hours per day consuming and digesting food, compared to our ancient ancestors who often ate only once per day and spent about 4 hours digesting their food. This results in the constant overexpression of mTOR and a severe deficiency in the activation of autophagy. I call this imbalance mTOR Syndrome.

Because cells are constantly receiving mTOR’s growth signals, they eventually become stressed and toxic. Cellular components become damaged because autophagy’s recycling, rejuvenation, detoxification, and renewal processes are not being activated.

Rebalancing the mTOR/Autophagy Ratio

The overexpression of mTOR (mTOR Syndrome) and the corresponding under expression of autophagy is increasingly being recognized as a fundamental mechanism underlying the onset of some of our most common age-related diseases. 5

Intermittent Fasting or Time-Restricted Eating

Intermittent fasting or time-restricted eating are dietary modifications that have been shown to effectively correct the out-of-balance mTOR/autophagy ratio.6 These programs don’t limit what you eat or how much you eat, they limit WHEN you eat. The goal is to consume all your daily calories in a shorter period of time, which allows more time for the activation of autophagy.

There are numerous ways to accomplish intermittent fasting or time-restricted eating. The 16:8 protocol is the most popular regime where food is consumed within an 8-hour period (noon to 8 PM). This leaves 16 hours without food intake, which allows autophagy to be activated.

Rapamycin: Human Clinical Trial

The human health benefits of taking rapamycin were documented in a study titled mTOR inhibition improves immune function in the elderly, which was conducted by Joan Mannick, MD. In this human clinical trial, people 65 and older who took 5 mg of rapamycin once weekly gained on average, a 20% boost in their immune system (complete details of the study are reviewed in my book). 7

This book also discusses how to monitor your rapamycin therapy, what side effects to be aware of, suggestions on how to get your physician to write a rapamycin prescription for you, links to key scientific studies, podcasts and interview with rapamycin scientists, a chapter on metformin, and a review of non-prescription mTOR inhibitors.

If you are interested in learning more about the rapamycin story, please use the following link to order the book “Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome”

For references or more info, please email Ross at



2Dasanu CA, Clark BA III, Alexandrescu DT. mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option. Expert Opin Investig Drugs. 2009;18(2):175-187.

3Afinitor (everolimus) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; March 2009.

4 Sabatini D, et al RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORS. Cell. 1994 Jul 15;78(1):35-43.

5 Klionsky D, et al. Autophagy in major diseases. EMBO J. 2021 Oct 1;40(19):e108863.

6 De Cabo R and Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. NEJM. 2019 Dec 26;381:2541-2551. 

7 Mannick J, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014 Dec 24;6(268):268ra179.