{"id":802,"date":"2019-02-05T17:23:41","date_gmt":"2019-02-05T17:23:41","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=802"},"modified":"2019-02-05T17:25:49","modified_gmt":"2019-02-05T17:25:49","slug":"rumors-of-age-reversal-the-plasma-fraction-cure","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2019\/02\/05\/rumors-of-age-reversal-the-plasma-fraction-cure\/","title":{"rendered":"Rumors of Age Reversal: The Plasma Fraction Cure"},"content":{"rendered":"

I say \u201crumors\u201d because there is no publication and results from just 6 rats, all of which were sacrificed for the sake of tissue biopsies. \u00a0Worse, we have no announcement of what the active agent(s) were that rejuvenated the rats, so discussion of mechanisms will have to wait. I\u2019m writing this largely from personal and scientific trust, while recognizing that even the most careful and honest scientists can deceive themselves. \u00a0\u201cYou are the easiest person to fool,\u201d Feynman warned us.<\/span><\/p>\n

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. \u00a0I\u2019ve 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. \u00a0Harold 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. \u00a0His 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. \u00a0He 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.<\/span><\/p>\n

The heretical idea that unites Harold\u2019s thinking and mine is this: \u00a0Aging 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. \u00a0This implies that aging isn\u2019t 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.\u00a0 The natural place to look for this communication of the age state<\/a> of the body is through <\/span>signal molecules in the blood<\/span><\/a>.<\/span><\/p>\n

\"\"<\/p>\n

Thus our hypothesis, Harold\u2019s and mine, is that even an old body remembers how to be young, if only it gets the message in the appropriate biochemical language. \u00a0If 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<\/a>, but they took a leap into the 21st century beginning in the Stanford laboratory of <\/span>Irv Weissman<\/span><\/a>. \u00a0His students spread out to Berkeley and Harvard, and the successors to these programs are studying the rejuvenation potential of various blood plasma components. \u00a0(It\u2019s not the red blood cells or the white blood cells. It\u2019s not any cells at all, but the proteins and RNAs and short peptides that are dissolved in the blood\u2019s clear liquid background, called plasma.) \u00a0Some 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 (<\/span>Ambrosia<\/span><\/a> and <\/span>Alkahest<\/span><\/a>) 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. \u00a0<\/span><\/p>\n

Harold doesn\u2019t have the funding or the university infrastructure that these people have, but by his report he has leapfrogged their research. \u00a0He 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\u2019re not all running like vampires after 20-something men and women, bidding up the price of their blood.<\/span><\/p>\n

His experimental results are preliminary, but impressive. \u00a0On the one hand, there are big questions that remain; on the other hand, I\u2019ve never seen success like this from any other intervention. \u00a0(The possible exception is the Mayo Clinic\u2019s 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.)<\/span><\/p>\n

So, what were the results that we find so impressive? \u00a0I\u2019ve linked to his own <\/span>chart of results<\/span><\/a>, and I\u2019ve asked Harold to tell us in his own words.<\/span><\/p>\n

To tell you the truth, when I first was invited by my partner, Akshay Sanghvi<\/a>\u00a0to conduct research at a laboratory in Mumbai (India, formerly \u2018Bombay\u2019) I had a very definite idea of what I wanted to do. \u00a0I wanted to transfer the plasma of a young rat, to replace the plasma of an old rat, which <\/span>I have called Heterochronic Plasma Exchange<\/span><\/a> (HPE). \u00a0This idea was originally based on heterochronic parabiosis, which apparently resulted in rejuvenation at the cellular level in mice, but without \u00a0the bizarre and cruel aspects of sewing two animals together; and yet, it should have more profound effects as 100% of the old animal\u2019s 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. \u00a0\u00a0If it is assumed that there are \u2018pro-aging\u2019 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 \u2018young\u2019 plasma. The greater concentration of youthful factors and the absence aging factors should push the cells and, eventually, the body to youthfulness. \u00a0<\/span><\/p>\n

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. <\/span><\/p>\n

Our first pass was to try a combination of known herbal supplements that are known to bind with the targets we\u2019d identified. \u00a0We 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. \u00a0We 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.<\/span><\/p>\n

We have addressed several different problems: <\/span><\/p>\n

    \n
  1. Identification and purification of youth-inducing factors and a process for their large-scale production<\/b>. Our processes are scalable from microliters to metric tonnes<\/span><\/li>\n
  2. Raw material supply<\/b>: we have gone beyond the need to obtain blood from young people, our sources are virtually limitless<\/span><\/li>\n
  3. Removal of the effects of \u2018pro-aging-factors\u2019.<\/b> \u00a0We have discovered a way to do that, one hidden in plain sight.<\/span><\/li>\n<\/ol>\n

    Here are <\/span>our results<\/span><\/a>. \u00a0Notice the striking and simultaneous occurrence of increases in mental speed and physical strength coupled with lower inflammatory markers and blood glucose levels. \u00a0Also 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. <\/span><\/p>\n

    Clearly, our next steps are <\/span><\/p>\n