Rapamycin: mTOR, autophagy and treating mTOR syndrome

Book that examines rapamycin and its role in slowing aging and increasing healthspan fully revised for second edition.

Ross Pelton, PhD, a pharmacist and certified clinical nutritionist with over three decades of research and scientific expertise, is renowned for his contributions to the field. Having authored ten books covering diverse health subjects and establishing the Natural Pharmacist website, Pelton’s dedication lies in educating individuals about health and life extension. This zeal has led him to delve into one of the most significant health subjects to date: rapamycin. Now his book on the subject has been fully revised and expanded in its second edition.

Rapamycin: mTOR, autophagy and treating mTOR syndrome

Longevity.Technology: Rapamycin is already often cited as the most effective antiaging drug currently available, and research into mTor – the mammalian target of rapamycin pathway – and rapalogs – synthetic drugs that are analogs of rapamycin – is moving fast.

Derived from bacteria found on Easter Island, rapamycin initially served as an immunosuppressant for transplant patients. However, it garnered attention for its anti-aging potential when studies revealed its ability to extend the lifespan of various organisms, including C elegans, flies and mice. Notably, a study published in Aging Cell showcased an up to 9% increase in mouse lifespan along with enhanced healthspan through rapamycin administration [1].

The mechanism of rapamycin revolves around inhibiting the protein mTOR, which regulates cell growth, proliferation, and the delicate balance between cell growth and death. By obstructing mTOR, rapamycin slows down the aging process and mitigates the risk of age-related ailments. Calorie restriction, known to extend lifespan and improve healthspan in mammals, is also believed to involve mTOR inhibition, making rapamycin a potential mimic of calorie restriction. Moreover, rapamycin promotes autophagy, a process that removes damaged cells and recycles their components, aiding in cellular homeostasis, as well as reducing inflammation and oxidative stress.

Ross Pelton’s book, Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome discusses the animal and human studies that document its effectiveness as a life extension drug and considers its therapeutic potential. A revised and expanded edition has just been printed as is winging its way to Amazon, Life Extension and other outlets – the Kindle version is already available from the Amazon store.

We caught up with Pelton to find out what the second edition has in store for its readers.

The mTOR/Autophagy Theory of Aging

Pelton describes mTOR and autophagy as the ‘yin and yang’ of cellular metabolism, and since the first edition of his book was published, he has continued studying and learning about mTOR and autophagy.

“These mechanisms are critically important regulators of cellular metabolism, health and biological aging,” Pelton says. “Autophagy is a critical regulatory mechanism of detoxification for every cell in the body and it also regulates the processes of rebuilding and renewing the body.  My increased understanding of the importance of mTOR & autophagy motivated me to propose The mTOR/Autophagy Theory of Aging in the second edition of my book.”

It is now well established that mTOR and autophagy are fundamental mechanisms that regulate cellular metabolism, health, and the aging process itself. Although there are many factors that influence biological aging, the mTOR/Autophagy Theory of Aging explains why these cellular mechanisms are critical factors that influence health and the aging process. The mTOR/Autophagy Theory of Aging integrates each of these processes and explains a fundamental mechanism of how the body detoxifies, recycles, and rebuilds itself throughout life.

A major cause of aging is the progressive accumulation of damaged macromolecules and components within cells. Types of damage appear as oxidized, misfolded, cross-linked, and/or aggregated proteins in cellular components, which have an abnormal structure that reduces or limits their ability to function properly. The health of an individual or organism depends on the ability to eliminate these old, dysfunctional cellular components and replace them with new, healthy cellular components. This process of degradation, recycling, protein synthesis, and renewal is regulated by autophagy and mTOR.

Humans have been evolving on Earth for several million years. Throughout most of human evolution, mTOR and autophagy were in balance. However, the mTOR/ autophagy ratio is severely out of balance in the majority of people alive today, and this imbalance is one of the main reasons mankind is experiencing an epidemic of chronic degenerative diseases.


Sarcopenia, which is the gradual loss of muscle mass as people age, is a major risk factor and biomarker of aging – and Pelton covers it in his book.

“Three factors that can slow down and/or reverse sarcopenia are dietary protein, strength training and rapamycin,” he explains. “The US RDA for protein is WAY too low. Many people suffer from protein malnutrition. I’m trying to educate people about these three factors that they can control to slow down the onset of sarcopenia.

A recently published paper reported that rapamycin reduces protein translation errors. This is an exciting new area of research because it presents another way that rapamycin improves health and extends lifespan. This mechanism is independent of rapamycin’s effect on mTOR and autophagy [2].

High-quality protein consumption, especially leucine, is important in order to optimize muscle protein synthesis. This is crucial for older individuals, especially those engaging in strength training, and particularly for people engaging in rapamycin therapy.

Highlighting Professor Vera Gorbunova’s research

Pelton’s book discusses the work of Professor Vera Gorbunova, who has studied how 10 established life extension drugs or therapies affect the genes associated with maximum life span in long-lived animals.

“The results revealed that rapamycin was the most effective at activating the genes associated with maximum life span –and it also had the least affect on genes associated with accelerated aging,” Pelton explains.

The results from Professor Gorbunova’s study revealed that rapamycin significantly reduced the activity of genes that have a negative effect on maximum lifespan. Rapamycin therapy also substantially increased the activity of genes positively associated with maximum lifespan.

Although Professor Gorbunova’s study was not a human clinical trial, it provides strong support for the claim that rapamycin is an effective life extension drug based on how it affects the genes associated with maximum lifespan.

Advocating for FDA reform

Pelton’s book advocates for FDA reform, urging his readers to lobby the FDA and/or Congress. He explains that the FDA views aging as a natural process, and consequently,
it does not allow aging to be classified as a disease.

“This policy limits and obstructs the ability to study aging since companies have virtually no chance of getting the FDA to approve clinical trials to evaluate drugs, biologics, or other interventions that may slow or reverse biological aging processes,” he explains.

Please speak up and make your voice heard. Contact your state and federal political representatives and request fast action on FDA reforms. And if you call or write, please be sure to emphasize your desire to have aging classified as a disease. The goal of medicine should be to help people attain and maintain good health for as long as possible. If the FDA would change its policy and allow aging to be classified as a disease, it would dramatically increase funding for aging research and the development of products that slow down the process of biological aging.

Currently, the annual budget for the National Institutes of Health (NIH) is about $45 billion. The National Institute on Aging (NIA), which is one of the 27 Institutes and Centers of NIH, has an annual budget of about $4 billion. Over 90% of NIH’s budget is devoted to research on individual diseases, and less than 10% is devoted to aging research through the NIA.

But if you take a close look at the NIA’s website, you’ll find that much of their funding is devoted to supporting and conducting Alzheimer’s disease research. This means that very little money is devoted to researching the fundamental process of aging.

If, like me, you’d like this to change, please become politically active. Call your political representatives and urge them to get the FDA to classify aging as a disease.

Rapamycin, mTOR, Autophagy & Treating mTOR Syndrome will shortly be on sale from Amazon, Life Extension and other outlets; the Kindle version is already available from Amazon.

[1] https://pubmed.ncbi.nlm.nih.gov/19587680/
[2] https://pubmed.ncbi.nlm.nih.gov/34525330/

Photograph: devotchkah/Envato