by Patrick Cox
April 29, 2018

Last week, I wrote the first part of this series to differentiate induced tissue regeneration (iTR) and geroprotectors. In a nutshell, it is the difference between rejuvenation and regeneration.

To recap, ITR is an approach to regenerative medicine based on the theory—and quite a bit of evidence—that our cells can perform an embryonic reboot.

Normally, when cells are damaged or wear out, they make their own replacements by copying themselves. Like a repeatedly duplicated photocopy, cells degrade with each additional reproduction.

ITR therapy would cause cells to access their original embryonic blueprint. Drawing on their original DNA instructions, they would create perfect, youthful cells instead of copying themselves. This is true regeneration, reversing the effects of injury and aging.

Few have predicted such a breakthrough except science-fiction writers and some long-forgotten scientists of the late 19th and early 20thcenturies. Even science-fiction writers tended to envision the arrival of radical regenerative medicine in the far distant future, well beyond the 21st century.

This may be because the societal, cultural, economic, and political consequences of age reversal would be so profound, it is difficult to imagine such a change. All disruptive medical revolutions, from germ theory to basic nutritional science, were initially vilified and doubted. True regenerative medicine is even harder to process.

So let’s examine a less radical concept: geroprotectors.


Geroprotection: Extending Healthspans for the Greater Good

Gero is the Greek root meaning age, and the term geroprotection reflects the goal of most biogerontologists, which is to protect people from the worst aspects of aging.

Since we’re reviewing the basic terminology, let me explain the term biogerontology.

In the past, the study of aging was generally divided into gerontology and geriatrics. Gerontologists study the physical effects of aging while geriatrics is the practice of caring for the aged. Biogerontology describes the subset of gerontologists who study the molecular mechanisms associated with biological aging.

Generally, the goal of biogerontology is not age reversal, which is rejected by many mainstream scientists. I’m convinced that this is primarily because they are still trying to convince policymakers and the public that aging can be slowed via geroprotection.

After decades of educational and scientific effort, scientists are finally beginning to get their core message across, and many fear that the concept of radical regenerative medicine will muddy the waters and set back their cause.

Their cause is to implement technologies and policies to extend healthspans while keeping the final stages of life when health deteriorates as brief as possible.

The following graphic comes from a longer discussion of this topic published in the journal The Physiological Society, titled, “Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity.”


Morbidity is the state of having a disease. The graph above illustrates morbidity compression,  that means reducing the end-of-life period spent in ill health and prolonging the time spent healthy and vibrant. Or, to put it another way, extending healthspans.

This is an important distinction. Polls have shown that most people don’t want life extension  because they assume it would simply tack additional years onto the end of their lives, when they are already frail and sick.

The goal of biogerontologists, however, is to keep us healthy and robust longer, and reduce the amount of time spent ailing and suffering at the end of our lives. The benefits would not only be personal—they would extend to personal and national finances because healthcare is our single largest expense.

Fortunately, there are a number of compounds that can accomplish that end. Called geroprotectors, they don’t involve age reversal. Rather, they fix underlying systems that break down as we grow older, accelerating aging and creating the conditions that lead to disease.


Rejuvenation Through Rapamycin

The most studied geroprotector is rapamycin. It’s been known for decades that animals given rapamycin, an antifungal compound produced by bacteria found on Easter Island, have lower rates of disease and longer lifespans.

This led to the discovery of the mTOR gene pathway. (mTOR is the acronym for mammalian target of rapamycin). For an idea of how much research has involved mTOR, search for the term using Google Scholar.

Geroprotection isn’t regenerative medicine. Regenerative medicine would turn back the clock of cellular aging by regrowing telomeres. Geroprotectors, on the other hand, can induce rejuvenation without resetting the telomere clock. This, I think, is the source of the confusion.

Rejuvenation, as opposed to regeneration, is the return to a healthier state. You might be healthier, stronger, and even look younger if some condition that has been dragging you down is resolved. It would also slow down telomere loss, extending both healthspans and lifespans.

We’ve seen this in animals and humans given rapamycin, which is an approved immunosuppressant used to prevent organ transplant rejection. Rapamycin works by reducing the activation of T cells and B cells involved in immune reactions against foreign substances.

Why would reducing immune reaction make one healthier? The reason is that the immune system is one of many biological systems that develop problems as we age.


Inflammation is the word used to describe an immune response, and it is now generally accepted that “Human aging is characterized by a chronic, low-grade inflammation, and this phenomenon has been termed as ‘inflammaging’.

That sentence is from a paper cowritten by the scientist most responsible for developing this theory of accelerated aging: Claudio Franceschi.

Inflammaging probably has two components. One is that our cells change over many replications and may look like injured cells to the immune system. Another part of the problem is that the immune system itself may be misfiring, finding false positives of injury or invasion.

The implication of Franceschi’s work is that we could reduce inappropriate immune responses to slow aging and reduce disease rates. Scientifically, this has been validated to a significant degree through animal tests with rapamycin. However, until recently, it was assumed that people would have to start taking rapamycin and other geroprotectors at a younger age to increase healthspans.

Fortunately, this has been shown to be false. Older animals given rapamycin experience a calming of inflammaging, which lowers stress on cells and leads to healthier tissues and apparent rejuvenation. While the animals’ cellular clocks aren’t turned back, their improved health and function makes them appear and behave as if they had been regenerated.

In fact, animals that were dosed when they were already old demonstrated most of the same benefits as animals given the compound starting at middle age. Of course, the impact on older animals, while slightly less, is much more dramatic. Most of us, after all, would like to have more youthful lives.

I’ve seen this process occur in people. One of the most obvious effects is restoration of some gray hair to its original color. Skin tone improves, as do other markers of age.


Japan’s Equivalent of Rapamycin

I recently had lunch with a relative whom I hadn’t seen since he had a kidney transplant about five years ago. Despite having had major surgery, which normally ages people, his skin and hair were noticeably improved.

He takes the immunosuppressant fujimycin, which, like rapamycin, is an anti-fungal compound produced by soil bacteria. It’s found in Japan and named after Mount Fuji.

I did a quick search to see if I could find scientists studying fujimycin for anti-aging impacts. I found nothing, but a lot of Japanese studies are unfortunately not translated into English, so that research may be taking place.

If you read the literature, you will also find out that fujimycin, like rapamycin, can cause side effects that mimic type 2 diabetes. We know why rapamycin sometimes produces those effects, and several companies are currently working on modifying the molecule to reduce that risk.

I don’t take rapamycin, by the way. I say this because I often get email from people asking me where I get mine. I know that some people do take the drug, often cycling to prevent T2D-like symptoms, but I know nothing about dosages, etcetera. That would require a well-informed doctor, which I’m not.


Geroprotectors You Can Use Right Now

I’m much more interested in the over-the-counter supplements that demonstrate similar impacts. The best-known, nicotinamide riboside, seems to have reached a kind of scientific tipping point, with mainstream physicians using and recommending it.

NR seems to have its biggest impact on the metabolic system, which develops problems with age, as do the neurological, endocrine, and circulatory systems. Of course, all of these systems are interconnected in ways that aren’t well understood, though we are getting tantalizing glimpses at the way repairing one system can have unexpected benefits. For example, a recent study showed that increasing blood circulation through Viagra can have powerful anti-cancer effects.

There are over-the-counter geroprotectors that address malfunctioning systems. The over-the-counter compound that has had the biggest palpable impact on my own health is vitamin D. Vitamin D is not actually a nutrient but a hormone that regulates other hormones and nutrients.


I’ve experienced noticeable improvements, especially in my workouts, from increasing consumption of nitrate-rich vegetables as well. I’ve also recently written about coffee, which truly qualifies as a superfood. As is often the case with powerful biochemical compounds, the trick with all three of these substances is getting the right dosage.

I suppose I should make a list for those of you who have been asking for it. I’ve hesitated, however, because this area of science is changing daily, so I would almost certainly have to issue constant revisions. Frankly, I’m much more interested in several drugs now moving through clinical trials for age-related diseases.

The companies behind these drugs know that they have the potential to be revolutionary geroprotectors, but they don’t want to attract the attention of skeptics or regulators. Nor do they want to scare off investors afraid of anti-aging medicine.

The good news, though, is that every day brings us closer to a true medical revolution. That revolution will be a combination of regenerative and geroprotective medicine, and we’re still learning what it will look like. Almost nobody, by the way, knows how quickly it’s coming.


— The Difference Between Anti-Aging and True Regenerative Medicine, Part 2: Geroprotection originally appeared at Mauldin Economics.