mTOR’s Role in Aging

Introduction

Dr. Joan Mannick is a medical doctor who studied how the body ages. She grew up in a family of doctors. She then chose a path in medicine, moved to research, and started looking at ways to keep people healthier as they grow older. Her work focuses on a protein called mTOR, which may help us understand why cells change with age.

In this blog post we will cover a podcast on her opinions on mTOR and Rapamycin, and their role now and in the future of anti aging.

Mannick’s Early Career and Motivation

Dr. Mannick came from a family where many relatives were doctors. She learned the value of hard work and helping others.

She thought about law and politics, but she saw that it was hard to pass new laws. By becoming a doctor, she felt she could help people more directly.

She worked at a lab and saw friends leave for private companies. They told her about new treatments that could be developed. She joined a large biotech firm at age 50.

What is mTOR and why It Regulates Aging?

mTOR is an evolutionarily conserved protein found in yeast, flies, worms, and mice. It helps cells respond to food intake by recognizing nutrients in the cell, switching on when animals eat and switching off during fasting.

Researchers have observed that blocking mTOR—either through genetic methods or by using the drug Rapamycin—extends the lifespan in these species. This effect appears alongside better health, which suggests that mTOR helps control the aging process. It is considered as “probably the best validated mechanism regulating lifespan”.

Different labs, doing research in a few different organisms on mTOR, have shown again whether genetically or with a single therapeutic called rapamycin, repeat this finding that not only is life span extended but these organisms live healthier and longer.

mTOR is unique with an enormous body of evidence. There isn’t any other molecule or protein that is giving the same results over and over again in different species.

It’s a big opportunity for modern medicine to figure out how can we use mTOR Inhibitors to help extend the human lifespan.

Because mTOR is so similar across different living things, and humans haven’t diverged genetically that much from these other species, there is a big opportunity for modern medicine to figure out how can we use mTOR Inhibitors to help extend the human lifespan and longevity. By finding ways to limit mTOR activity in safe ways, scientists hope to help people stay healthier as they grow older.

Rapamycin: A Drug That Targets mTOR

Rapamycin was a natural product found in the soil on Easter Island. Rapamycin was first found to block fungal growth, so it was initially tested as an anti-fungal drug.

Scientists then realized it also blocks the T cells which are critical immune cells. In organ transplant patients, the body stops rejecting transplanted organs, when T cells are blocked. Rapamycin became an immunosuppressive treatment for transplant patients.

Rapamycin, blocking (inhibiting) T Cells were also found to affect cancer proliferate (spread).

When mTOR is blocked, the body can not build blocks to grow. Instead, protective pathways are activated, and excess garbage molecules like cancer cells or fungus are broken down. As organisms (and mammals alike) age, mTOR does not shut off anymore as it used to; therefore, garbage molecules accumulate in cells, creating a loop in aging. Rapamycin regulates mTOR, and this loop is overridden by breaking down excess cells.

The Most Explored Organism for Rapamycin is Humans

The strongest data with Rapamycin is yeast flies and mice and recently there is a new study generating data in aging dogs as well. These are the clinical model organisms for Rapamycin’s impact on longevity.

In practice, the most studied model organism is not a model organism, rather it’s humans. Rapamycin is approved and has been used in thousands of transplant patients and thousands of cancer patients.

mTOR inhibitors are being used in clinical trials in almost 2000 older adults. So “more humans now have been treated than probably the sum of all the mice that have been treated”, Dr. Mannick claims.

Dr Mannick part a role in finding the missing opportunities in anti-aging during her career in Novartis. She chosed to work on aging, with mTOR inhibitors in human trials. With a relatively quick clinical trial time frame, they saw that older adults had better response to flu vaccines with low doses of mTOR inhibitors.

After noticing at the end of the trial is the people who are getting the M2 Inhibitors were having fewer respiratory tract infections than the people who were getting placebo; Dr. Mannick started a second study and found out that people getting mTOR Inhibitors were having fewer all-cause infections, compared to people on placebo. Older adults that are treated with low doses of mTOR inhibitors developed better antiviral immunity.

Why mTOR Matters for Healthy Aging

Nutrient sensing: mTOR turns up when you eat and turns down when you stop eating. With age, mTOR can stay “on” more than it should.

Cell cleanup: When mTOR is lower, processes that clear out waste in cells may work better. This is good for older cells.

Strong support: Different labs have tested mTOR blockers in many species. Each time, animals have lived longer. That makes this research very hopeful for people.

Caution and Looking Ahead

There is no clinical data on who should be taking Rapamycin, at what age, in what dose, for what duration, what it helps, and what it does not help. Clinical studies take 10 to 15 years to get to such confidence.

Seeing the progress now, Rapamycin may be used for respiratory system infections in the coming 5 years for elderly. Adding clinical trials for other aging organs like heart, or tissues like muscles and for cognitive functions on the later years, Rapamycin may be considered as an anti aging drug.

Conclusion

Dr. Joan Mannick’s work shows that mTOR may be a promising path toward better health in later years. Careful testing is needed, but her findings suggest that blocking mTOR could help the body defend itself against infections and possibly slow other effects of aging. For now, common-sense habits like exercise and balanced eating remain the best steps for supporting longer and healthier lives.