I say “rumors” because there is no publication and results from just 6 rats, all of which were sacrificed for the sake of tissue biopsies. Worse, we have no announcement of what the active agent(s) were that rejuvenated the rats, so discussion of mechanisms will have to wait. I’m writing this largely from personal and scientific trust, while recognizing that even the most careful and honest scientists can deceive themselves. “You are the easiest person to fool,” Feynman warned us.
Some of you may recognize the name of Dr Harold Katcher, who is one of the most prolific and best-informed among many well-informed readers commenting on this blog. I’ve known Harold for about 10 years. We came together because we have the same idea about what aging is. The difference is that I have only the evolutionary reasoning, the logical shell. Harold also has the background in biochemistry to fill in the details. Filling in the details is what he has been doing, and this week he convinced me that he has the most promising age-reversal intervention yet devised. His treatment protocol is in preliminary stages of testing, and because the ideas that he and I share are out of the mainstream, it has not been easy for him to get funding. Now that he has preliminary results, perhaps that is about to change. He is committed to bypassing the standard channel of Big Pharma, proceeding on his own with appropriate partners to assure that the the technology gets to a wide public at affordable prices–but it is early to think in these terms.
The heretical idea that unites Harold’s thinking and mine is this: Aging is controlled through evolutionarily conserved mechanisms. Some of the same genes and proteins that control the rate of aging in yeast cells serve the same function in mammals, which may live a thousand times longer than yeast. This implies that aging isn’t just random damage to individual cells; rather it is tightly regulated at the systemic level. Maybe there is a central clock, or maybe there is a consensus that is reached body-wide. But in any case, there is communication, assuring that different parts of the body keep to a common schedule. The natural place to look for this communication of the age state of the body is through signal molecules in the blood.
Thus our hypothesis, Harold’s and mine, is that even an old body remembers how to be young, if only it gets the message in the appropriate biochemical language. If an old mouse were to have the blood of a young mouse coursing through its veins, the old mouse would become a young mouse. Parabiosis experiments, sewing together mice of different ages so that they share a common blood supply, originated in the 19th century, but they took a leap into the 21st century beginning in the Stanford laboratory of Irv Weissman. His students spread out to Berkeley and Harvard, and the successors to these programs are studying the rejuvenation potential of various blood plasma components. (It’s not the red blood cells or the white blood cells. It’s not any cells at all, but the proteins and RNAs and short peptides that are dissolved in the blood’s clear liquid background, called plasma.) Some of the best-known people working on this idea are Mike and Irina Conboy at Berkeley, Amy Wagers at Harvard, Tony Wyss-Coray at Stanford. Two companies (Ambrosia and Alkahest) have begun selling transfusions of young blood to wealthy old folks, brave or desperate enough to experiment on themselves with untried technology, and to pay for the privilege.
Harold doesn’t have the funding or the university infrastructure that these people have, but by his report he has leapfrogged their research. He claims to have isolated the crucial molecules in young blood plasma, and that it is feasible in the not-too-distant future to synthesize them, so we’re not all running like vampires after 20-something men and women, bidding up the price of their blood.
His experimental results are preliminary, but impressive. On the one hand, there are big questions that remain; on the other hand, I’ve never seen success like this from any other intervention. (The possible exception is the Mayo Clinic’s work with senolytics, extending the lives of older mice; but the two approaches are so very different and what we know about the two is so different that there is no basis for saying one is more successful or more promising than the other.)
So, what were the results that we find so impressive? I’ve linked to his own chart of results, and I’ve asked Harold to tell us in his own words.
To tell you the truth, when I first was invited by my partner, Akshay Sanghvi to conduct research at a laboratory in Mumbai (India, formerly ‘Bombay’) I had a very definite idea of what I wanted to do. I wanted to transfer the plasma of a young rat, to replace the plasma of an old rat, which I have called Heterochronic Plasma Exchange (HPE). This idea was originally based on heterochronic parabiosis, which apparently resulted in rejuvenation at the cellular level in mice, but without the bizarre and cruel aspects of sewing two animals together; and yet, it should have more profound effects as 100% of the old animal’s blood could be replaced–while in heterochronic parabiosis, a young rat is half the weight of an old rat, so that the combined plasma circulation in the parabiots is considerably less than 50% young plasma. If it is assumed that there are ‘pro-aging’ factors in the blood plasma of old animals, those factors would remain. By using HPE however, sufficient rounds of plasma replacement should leave the old animal with nearly pure ‘young’ plasma. The greater concentration of youthful factors and the absence aging factors should push the cells and, eventually, the body to youthfulness.
Although transfusion technologies for humans are mature and quite safe, transfusing small animals requires state-of-the-art lab techniques. Try as we might, we could not perform plasma exchange in rats. Time was growing short (I was on a two-month visa) so what to do? I made the decision to completely change my approach: yes I believed HPE would work, but I decided to leap ahead, to see if we could make the process of HPE into a marketable product.
Our first pass was to try a combination of known herbal supplements that are known to bind with the targets we’d identified. We gave them to rats, and at first nothing seemed to be happening. But after two months (about 4 years in human terms) the rats showed signs of rejuvenation. We were encouraged. Rather than continue with the herbs, though, we formulated the elixir that we report on here. This is our first iteration, with dosage and timing determined theoretically, yet to be optimized in the lab.
We have addressed several different problems:
- Identification and purification of youth-inducing factors and a process for their large-scale production. Our processes are scalable from microliters to metric tonnes
- Raw material supply: we have gone beyond the need to obtain blood from young people, our sources are virtually limitless
- Removal of the effects of ‘pro-aging-factors’. We have discovered a way to do that, one hidden in plain sight.
Here are our results. Notice the striking and simultaneous occurrence of increases in mental speed and physical strength coupled with lower inflammatory markers and blood glucose levels. Also encouraging is that these changes began days after the IV treatment, and the markers that were improved but not quite down to youthful levels continued to improve right up until the day of their sacrifice. It would appear that the changes induced are permanent, but it will take additional experimentation to confirm this.
Clearly, our next steps are
- repeating and extending our rat results to include molecular and epigenetic signs of aging (Steve Horvath is developing a methylation clock for rats).
- extending results to dogs (in collaboration with Dr Greg Fahy)
- Looking for other molecular changes, including telomere length and various mitochondrial parameters
- and, of course trying the elixir in humans.
I am looking ahead to envision an elixir that brings you back to apparent youth in a week and a day with no side effects. Time will tell, but I feel that the results we have at this point justify optimism.
— Harold Katcher
I’m full of questions, but Harold tells me these will have to wait until intellectual property is secured.
- For some interventions, the body is made stronger and levels of tissue growth repair are restored to youthful states, but there is a cost in elevated cancer risk. This is something that will take time to determine, and perhaps working with mice would be better, since they have higher cancer rates than rats.
- I would guess that a fully youthful phenotype will require restoration of the thymus, which shrinks severely with age both in rats and humans. The current report doesn’t mention thymic regrowth.
- What would rejuvenation look like in humans? Physical strength and mental acuity are a great start. Would my eye lenses soften to youthful levels? Would I grow new discs between my vertebrae (and regain the 2″ I’ve lost in the last decade)? How about teeth and hair?
- I’ve read that many blood factors are transient, with a half-life of seconds to minutes. I can imagine long-term effects from epigenetic reprogramming through blood factors, but I’m surprised this could happen without a continuous IV feed.
- And, of course, I’m curious about the content of the elixir. Thousands of different compounds have been isolated from blood plasma, and hundreds that differ between young and old. I think of the Conboys as leaders in this field, and when I spoke to them less than two years ago, they had been unable to identify a small subset of key factors that would induce changes in the rest. Harold has said, “these factors are ‘bio-similar’ to factors already present in the blood, they work by natural means…”
The bottom line
I respect Harold’s caution in protecting his discovery out of the reach of Big Pharma. On the other hand, so many questions are not being addressed because his resources are limited. This is indeed a very promising start, and let’s hope that the appropriate connections come along so that further experiments can proceed without delay.