WHAT IS THE RAPAMYCIN/SENOLYTICS ANTI-AGING PROGRAM?
This is a program that looks at the efficacy of FDA-approved drugs as well as non-FDA approved therapies that are believed to have anti-aging effects. Specifically, we will focus on:
- The medication Rapamycin
- The “Senolytics” Dasatinib and Quercetin (“D+Q”)
- The coenzyme NAD+ which helps our cells make energy
- Stem Cell and Exosome therapies
All of these are explained further below. We will be tracking the efficacy of these interventions by testing your DNA methylation patterns. This, too, is explained further below.
PEOPLE HAVE BEEN TOUTING “ANTI-AGING” THERAPIES FOR DECADES. HOW IS THIS PROGRAM DIFFERENT?
As melodramatic as it sounds, we are actually at a turning point in human history. Until May 2020, no accurate testing method was commercially available to determine whether “anti-aging” interventions were effective. Many such tests have been proposed over the years (such as Telomere length, or algorithms of various blood markers), but there was no scientific consensus that any of those tests could be reliably used for anti-aging research. That has changed: there is now a commercially available test that can tell us whether a given intervention is slowing the aging process. It is a sophisticated measurement of DNA methylation, based off of Steve Horvath’s “methylation clock,” which was first proposed in 2014 and revised in 2018. Read more about the methylation clock here and here. Read more about the new DNA methylation test, TruAge, here.
I’VE HEARD OF A TEST CALLED MYDNAGE, ISN’T THAT THE SAME THING?
MyDNAge is based on the earliest (2014) version of Steve Horvath’s methylation clock. However, the algorithms have been significantly expanded and improved since then. MyDNAge was never accepted within the scientific community as a research tool. TruAge is much more accurate.
WHAT IS RAPAMYCIN?
Rapamycin, also called sirolimus, is an FDA-approved prescription medication that has been used since 1999 to prevent organ rejection in people getting kidney transplants. It is also used as a coating in stents that go into people’s coronary arteries, and in 2015 it was also approved as the first medication to treat a rare lung disease called lymphangioleiomyomatosis.
However, the reason we are interested in it is: when used in very low doses, Rapamycin is also the only known compound that reliably increases the lifespan of every type of living creature it has been tested on: yeast, worms, flies, and mice. Rapamycin has also been tested in older dogs and improved their heart function after just a few weeks. Currently, a five-year anti-aging study is underway using rapamycin for dogs, called the Dog Aging Project. Many biohackers, early-adopters, and scientists are interested in learning whether Rapamycin can slow the aging process in healthy humans as well.
WHAT DOES RAPAMYCIN DO?
Surprisingly, all known species have a receptor for rapamycin in our cells. That receptor, conserved across two billion years of evolution, has been named the molecular Target of Rapamycin, or mTOR. Rapamycin has only one action: it binds to TOR and thereby lowers TOR activity. TOR controls the aging process within our cells. Therefore, rapamycin may be able to slow the aging process.
WHAT ARE “SENOLYTICS”?
“Senescence” is the process of deteriorating with age. “Cell senescence” refers to when a cell stops dividing and starts secreting messengers that increase inflammation. Although senescent cells exist in relatively small numbers in all of our organs, they are associated with multiple diseases of aging and are emerging as useful therapeutic targets for age‐related diseases, including cardiovascular disease, pulmonary fibrosis, neurodegeneration, and osteoporosis. In other words: getting rid of senescent cells has become a new therapy that has gotten a lot of attention recently. Medications or supplements that get rid of senescent cells are called “Senolytics.” The ones we are using are the ones being studied most closely: the medication Dasatinib and the supplement Quercetin (“D+Q” for short). Many mouse studies have been done on this combination, and in 2019 two human studies were published using D+Q for senolytic therapy. Both studies were carried out in the United States, one by the Mayo Clinic. Both studies reported positive results. Some researchers are also looking at Fisetin instead of Quercetin and we may use that as well for some patients.
You can read more about the studies on Dasatinib and Quercetin here and here.
ARE THERE ANY STUDIES ON HUMANS?
Rapamycin has been an FDA-approved drug since 1999, so multiple controlled studies have been carried out and many thousands of patients have received it. However, it is very challenging to study medications in humans, specifically for anti-aging. One problem is: humans live a very long time. (That’s why the Dog Aging Project was started: to speed things up. The hope is that in five years, using dogs, they can learn more about the aging process than we could learn in 25 years using humans.) Currently, no studies have been completed on any medication or supplement specifically to study whether it is “anti-aging” in humans. While there is great interest in the diabetes drug Metformin and whether it can slow aging, it will be many years before any human studies specifically for anti-aging are complete. There are small, controlled human clinical trials getting under way in 2021 to determine whether Rapamycin, D+Q, Stem Cells/ Exosomes, and NAD+ have anti-aging effects. (These are the same medications this program is using). Those studies will be run by the Better Humans Project. Also, in 2019 two human studies were done using the senolytics Dasatinib and Quercetin, and those studies were tangentially about anti-aging. (They were short-term studies to see if some markers of aging improved.) Both of those studies had very encouraging results; see “What Are Senolytics” (above).
WHAT ABOUT METFORMIN? ISN’T THAT BEING STUDIED AS AN ANTI-AGING DRUG?
The reason people are interested in the effects of the diabetes drug Metformin on aging is, metformin indirectly inhibits mTOR. (Rapamycin has a much more direct and more powerful effect on mTOR.) While there is great interest in whether Metformin can slow aging, it will be many years before any human studies specifically for anti-aging are complete. Instead, researchers look at whether Metformin will lower cancer risk or lower heart disease, and based on those results they try to infer whether it is slowing the aging process.
A second problem with anti-aging studies in humans is: until recently, there has been no consensus as to how to measure results. It is only within the last couple of years that some consensus is forming around the use of DNA methylation testing to track the aging process…and only as of May 2020 is such testing available to the public! So, we are in many ways at the dawn of a new era, in which we can actually validate or refute whether a given therapy is truly “anti-aging” or not.
You can read more about Epigenetics in this Discover Magazine article. Read more about biological age (also called Epigenetic age) here.
IS DR. TRUTT RUNNING A FUNDED RESEARCH STUDY?
No, you would be paying for all of your own medications and visits. The results may or may not be published. The main information you will gain is whether these interventions are effective in you.
Of note, there will be some small, controlled human clinical trials getting under way in 2021 to determine whether Rapamycin, D+Q, Stem Cells/ Exosomes, and NAD+ (i.e. the same medications this program is using) have anti-aging effects. Those studies will be run by the Better Humans Project.
WHO IS THIS ANTI-AGING PROGRAM FOR?
People between the age of 45 and 90 who are looking to lower their risk of age-related diseases. People who enroll in this program should be comfortable using medications or supplements that are not yet proven to be effective for anti-aging in humans.
WHO IS NOT RIGHT FOR THIS PROTOCOL?
- This is not an appropriate protocol for women who are still hoping to get pregnant.
- If you are beyond age 90, current theory is that Rapamycin will no longer be helpful. However, Dasatinib+Quercetin (“D+Q”), Elamipretide, Stem Cells and NAD+ may still be helpful in people over the age of 90.
- I’m allergic to Erythromycin. Can I take Rapamycin? Probably. The two do not necessarily cross-react. However, depending on the severity of your allergy to erythromycin, we might proceed with caution.
WHAT IS THE TREATMENT PROCESS?
The basic protocol is as follows:
- Perform the TruAge DNA methylation test to determine your epigenetic age at the start. We will do this in our office. It is a simple blood test.
- Use D+Q three days a week for two weeks; then use Rapamycin one day a week for six months. Repeat.
- For some patients, NAD+ iontophoresis patches or the peptides may be included in their protocol
- After at least four months have passed, re-check the DNA methylation test to determine the protocol’s effect on aging.
WHAT RESULTS CAN I EXPECT?
We hope that, no matter your age, your DNA methylation patterns will show that we are slowing the aging process. However, we won’t know until we try!
As far as what you can feel or see: This will be highly variable, depending on your age and medical issues.
Rapamycin is not a “weight loss drug,” but it does make it easier to lose the weight that gradually accumulates with age. One fairly consistent effect of Rapamycin is an improvement in waist-to-hip ratio in those who need help with that.
We also expect to see an improvement in insulin levels and a decrease in non-alcoholic fatty liver (NAFLD).
Many of the treatments we are using have animal or human studies showing improvement in Osteoarthritis, Heart Disease, or Alzheimer’s risk, so any of those benefits are possible– but we won’t know until we try.
As for anecdotal reports: We have had anecdotal reports from our patients taking Rapamycin of a decrease in the amount of grey hair– and we hope that is a repeatable result, but we will need more patients to determine that. Many of our patients have reported improved healing and more energy and a sense of well-being after using stem cells.