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Is Rapamycin the Fountain of Youth?

I’ve always been interested in genetics. The body’s use of our genetic code to regulate every bodily process is fascinating. So, I’m naturally fascinated by the concept that our genes and/or the pathways that rule all of our cell function can be altered for our benefit. The million-dollar question in anti-aging research is: Can we target aging biology in humans with a drug or substance?

I believe the answer is, yes. That is where mTOR comes into play, as regulating mTOR has shown the most promise in the ability to modulate aging. mTOR (mammalian target of rapamycin) is an evolutionarily conserved protein, meaning it is seen in all species (worms, mice, yeast, dogs, humans) and seems to function the same across those species. mTOR regulates how our body responds to nutrients.

To simplify it, when you eat, mTOR is turned “on” and when you fast, mTOR is turned “off”. When mTOR is “on”, it turns on a domino of pathways that lead to cell replication—it tells your body to create building blocks for growth. When mTOR is “off”, alternate pathways are upregulated. One pathway that gets upregulated, is autophagy.

Autophagy has become a buzzword in the anti-aging world, largely due to intermittent fasting research. Many benefits of intermittent fasting are due to an increase in cell autophagy. Autophagy is regulated cell death. Essentially, you can think of it as your body’s recycling system. When the autophagy pathway is upregulated, your body identifies cells that are unhealthy or too old to function appropriately, and it destroys those cells. The pieces of those cells go into lysosomes (do you remember those from 7th grade science?). Lysosomes are the recycling plants of the cell. We’ll talk more about intermittent fasting in another post, but you get the idea: Autophagy (regulated cell death) is a good thing.

As we age, mTOR gets hyperactive in certain body tissues and it can actually stop responding to fasting. It essentially just stays in the “on” position. (This has been shown in mice) This means, there is no time for the protective pathways (like autophagy) to be active. There is no definitive age when this happens. It seems to vary. Some studies have found that it’s in over 65-year-old people, and others have found it largely occurs closer to age 75. The discrepancy is likely because it won’t be the same for every person. If someone has exercised and eaten a plant-rich diet and slept really well, their cells and cellular pathways are likely better preserved than those who rarely got a full night’s sleep, regularly ate processed foods and never increased their heart rates.

Why is mTOR all the rage in anti-aging? Rapamycin.

Rapamycin is the newest longevity/healthspan darling drug. Its origin story is an interesting one. It was discovered in the soil on Easter Island. It was originally found to inhibit fungal replication, so was first used as an anti-fungal drug. But it was also found to inhibit the replication of T-cells (cells important in the function of the immune system). Decreasing T-cell function is paramount for transplant patients—if T-cells aren’t inhibited, the transplant patient’s immune system will attack the newly-transplanted organ. Rapamycin was also found to inhibit growth in cancer cells, and so several derivatives of it have been used in chemotherapy.

It was shown that Rapamycin inhibits cell growth by turning mTOR to “off”. And while higher doses of Rapamycin inhibit the immune system, lower doses of mTOR inhibitors have been found to actually improve immunity. Essentially every trial using low dose mTOR inhibitors has shown improved anti-viral immunity in people over 75-years-old. What’s more, Rapamycin has actually been shown to increase lifespan significantly in flies and mice and early studies are showing the same effect in dogs. These results aren’t just exciting, they’re ground-breaking. No substance has ever been shown to increase lifespan in a mammal and the results be repeatable in multiple labs. We’re used to hearing of more obscure studies that other labs have not been able to replicate, such as the case with Resveratrol. Also, while mice results can be impressive, dogs are much closer to resembling humans biologically.

So, should you go out and start taking Rapamycin to live better forever? Maybe not just yet, though some are taking rapamycin at low doses hoping to replicate the life-extension and potential age-reversal in cells and organs. As of now, we have no studies showing a safe and effective low dose in healthy adults. On the flip side, there is long-term data on it's safety in transplant patients. It’s important to consider at what age an mTOR inhibitor could be used safely to prolong life and slow down cellular aging since mTOR is involved in growth.

Further, just because something works in a mouse doesn’t necessarily mean it will work in a human. We have cured cancers and Alzheimer’s in mice but are far from achieving that in humans. However, it is encouraging that Rapamycin’s target (mTOR) appears to work the same in each species, which is often not the case with other drug targets. And, as mentioned above, several trials have already shown mTOR inhibitors to improve immunity in those over 75.

There is a lot to be excited about, as the next 5-10 years will likely reveal much more about Rapamycin’s (and other mTOR inhibitors') effects on the various organs of the body. If it can be shown to not only improve immunity, but to improve other organ system function (such as heart, brain, kidneys) then it could truly be the proverbial fountain of youth, and might be in the medicine cabinets of all those looking to push the limits of human healthspan.


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