- \n
- The principal treatment consists in 6 plasma transfusions scheduled over 4 weeks.<\/span><\/li>\n
- Extensive testing is planned, including telomere age<\/a> and methylation age<\/a> in addition to a full battery of standard blood tests like lipids and inflammation markers.<\/span><\/li>\n
- The program is self-funded by research subjects, with projected cost ~ $50,000 per participant.<\/span><\/li>\n
- In each transfusion procedure, red and white blood cells will be separated and cycled back into the subject. \u00a0Blood plasma with dissolved blood chemicals will be removed. \u00a0It will be replaced not by full plasma from a donor but by albumin and gamma globulin only.<\/span><\/li>\n<\/ul>\n
\n\u201cRescue Elders\u201d project of LEF <\/b><\/p>\n
Last year, <\/span>Life Extension Foundation<\/span><\/a> announced a new and ambitious program of human experimentation at the edge of medical science, sponsoring high-risk trials to prospect for anti-aging breakthroughs in the near term. \u00a0(The project\u2019s name, <\/span>Society for the Rescue of our Elders<\/span><\/a>, was taken from an 18th Century group in Amsterdam, Society for Recovery of Drowned Persons, that was formed after the efficacy of artificial respiration was first discovered.) \u00a0Their first project was a clinical trial of rapamycin, now ongoing. \u00a0This present program of plasma transfusions is their second project.<\/span><\/p>\n
<\/p>\n
Target: Epigenetics<\/b><\/p>\n
It\u2019s my belief that the body\u2019s primary aging clock is epigenetic. \u00a0That is to say, different combinations of genes are expressed at different times in life, and in old age the constellation of genes that is turned on causes inflammation, auto-immunity, and a preponderance of anabolism over catabolism. \u00a0The master\u2019s tools are deployed in old age to <\/span>dismantle the master\u2019s house<\/span><\/a>.<\/span><\/p>\n
As a general concept, I think this is the best working hypothesis we have. \u00a0But if it is correct, it doesn\u2019t offer an immediate key to rejuvenating the body. \u00a0The problem is that epigenetics is enormously complicated. \u00a0(The genetic code, in contrast, is as simple as it can be\u2014a code of correspondence between triples of nucleic bases in the DNA with the 20 amino acids that are linked together, then folded to form proteins.)<\/span><\/p>\n
Methylation of chromosomes is the best-known and first-discovered mechnism by which genes are turned on and off. \u00a0In addition to methylation, there are dozens of other epigenetic markers and signals that are applied directly to DNA or indirectly to the histone spools, beads of protein that around which DNA is coiled.<\/span><\/p>\n
Different genes are turned on in different parts of the body. \u00a0This is the primary way that the body differentiates one kind of cell from another\u2014they all have the same genes, but different combinations of genes are turned on in a nerve cell or a muscle cell or a skin cell. \u00a0Overlayed on these differences from one cell type to another, genes are turned on and off with age. This effect is reliable and consistent enough that Steve Horvath was able to construct a <\/span>methylation clock<\/span><\/a> based on 353 methylation sites that change consistently with age across all cell types in the body.<\/span><\/p>\n
The connection to blood signals was supplied by research from <\/span>Stanford<\/span><\/a>, <\/span>Berkeley<\/span><\/a> and <\/span>Harvard<\/span><\/a>, in which blood from a young mouse is introduced into an old mouse, and is shown to rejuvenate its tissues, stimulate new growth, and promote healing. \u00a0With a small conceptual leap, I imagine that there is a <\/span>self-regulating epigenetic clock<\/span><\/a> distributed through the body. \u00a0On the one hand, epigenetic markers in each cell give each cell its characteristic age. \u00a0On the other hand, these same cells are sending signals though the blood (transcription factors) that are continually updating the epigenetic program and keeping it in sync throughout the body. \u00a0The hope is that (even if we don\u2019t understand in detail how the epigenetics is programmed) the substitution of a young blood environment for an older blood environment will reprogram epigenetics in the distributed cells, and after a few cycles it will be self-sustaining. \u00a0That is, once the cells are reprogrammed to be younger, they will themselves send signals into the blood that maintain the younger state.<\/span><\/p>\n
![](\"https:\/\/fuentedelaeternajuventud.files.wordpress.com\/2014\/06\/parabiosis.jpg\")
<\/p>\nCriticism of the protocol<\/b><\/p>\n
Here is a <\/span>description of the proposed YBI protocol<\/span><\/a>. \u00a0Six times over a period of 4-6 weeks, patients will be hooked up to a plasmapheresis machine. \u00a0Whole blood is removed from one arm, and a mixture is returned to a vein in the other arm. \u00a0The mixture that is returned will include all the patient\u2019s own red and white blood cells. \u00a0But the blood plasma, clear liquid with all the dissolved signal molecules, will be removed. \u00a0The plasma will not be replaced by blood plasma from a younger patient, as in a standard plasma transfusion. \u00a0Instead, the return side will contain only albumin and gamma globulin. \u00a0These are the hydrostatic and immune components of the plasma (antibodies). \u00a0The theory is that auto-immune aspects of aging will be addressed in this way…but the antibodies are generated continually by white blood cells, so that the treatment will not last long. \u00a0Hence the rationale for frequent repetitions of the treatment, less than a week between treatments.<\/span><\/p>\n
![](\"https:\/\/www.partnersinwellnessinc.com\/wp-content\/uploads\/2017\/08\/Patient_MCS_2.jpg\")
<\/p>\nMy principal fear is that the planned YBI protocol may be able to do only half the job. \u00a0My conjecture is that it is the signal molecules that actually maintain the epigenetic program. \u00a0The proposed protocol will remove the bad ones, and that\u2019s half the job. \u00a0It may be that there are transcription factors from young blood that are deficient in the old and need to be replenished. \u00a0Full plasma transfusions from young donors would do both, fully replacing the blood environment of an old person with the blood environment of a young person. \u00a0But it is expensive and requires many donors for each patient. \u00a0It is to control expense that YBI has chosen to do do the removal, but not replacement of blood signal molecules.<\/span><\/p>\n
Just last year, Tony Wyss-Coray headed a <\/span>Stanford trial<\/span><\/a> for AD, through a for-profit spinoff called <\/span>Alkahest<\/span><\/a>. \u00a0Alzheimer\u2019s patients were given four doses of young blood plasma. \u00a0But the dose was small, a total of 1.5 liters of plasma, and the bad actors weren\u2019t being removed. \u00a0Results were disappointing, but perhaps this is because the procedure was not bold enough.<\/span><\/p>\n
<\/p>\n
Promising Precedent<\/b><\/p>\n
Beginning in 1924, a Soviet Bolshevik named <\/span>Alexander Bogdanov<\/span><\/a> experimented on himself, receiving a series of 10 blood transfusions from younger donors. \u00a0He was 51 years old at the start of the experiment, and contemporaries report that he appeared physically ten years younger in the course of the procedures. \u00a0He self-reported prodigious health benefits and return of youthful vigor. \u00a0The experiment ended tragically in 1928, when he received blood from a student who had been infected with malaria, and died of the infection. \u00a0<\/span>
![](\"https:\/\/steemitimages.com\/0x0\/http:\/\/savepic.ru\/11979889.jpg\")
<\/span><\/a><\/p>\nHarold Katcher has been thinking about the rejuvenation potential of plasma transfusions for a long while, and <\/span>here is the protocol<\/span><\/a> he suggested five years ago. \u00a0He does not speculate about what schedule would be ideal, and he cautions us that extensive experimentation with mice and even in cell cultures would be useful before beginning human trials.<\/span><\/b><\/p>\n
Unpromising Precedent<\/b><\/p>\n
Two years ago, I spoke via skype with Jesse Karmazin (Stanford University and <\/span>Ambrosia<\/span><\/a>). \u00a0He told me that as a med student he had done an analysis of historic data from transfusions performed at Stanford University Hospital, and found that those who had received blood from young donors had better outcomes and better long-term survival rates than those whose blood had come from older donors. \u00a0I was very interested in this claim, and asked him for the data that supported it. \u00a0He told me it could not be released for reasons of patient privacy. \u00a0I never did get to see that data, and he never published his analysis.<\/span><\/p>\n
Last year, a <\/span>published study<\/span><\/a> claimed the opposite: \u00a0that in a large database of Swedish and Danish patients transfused between 1995 and 2012, they were unable to detect any survival difference between those who received blood from young donors and a matched group of patients whose transfused blood came froun old donors.<\/span><\/p>\n
<\/p>\n
Questions<\/b><\/p>\n
Ideally we would like to learn many details from a trial of HPE (heterochronic plasma exchange). \u00a0Fundamentally, we would test the basic question whether circulating factors in the blood are indeed able to reprogram the epigenetics of cells throughout the body, and whether this will have a salubrious effect on vitality, appearance, metabolism and the immune system. \u00a0A well-designed trial might also teach us more<\/span><\/p>\n
- \n
- Which chemical components (proteins and RNAs) are most important to be removed<\/a> from the blood of older people?<\/span><\/li>\n
- Which chemical components (proteins and RNAs) from young donors are most effective to be added<\/a> back?<\/span><\/li>\n
- How long does the young plasma profile remain in the bloodstream before the body\u2019s old cells take over and drag the proportions back down to where they were? \u00a0(At this point, the next infusion would be appropriate.)<\/span><\/li>\n
- How many transfusions are required before the body\u2019s cells are reprogrammed, and the young plasma profile becomes self-sustaining?<\/span><\/li>\n<\/ul>\n
Transfusions from young donors are a good place to start, but obviously not a practical solution for rejuvenating large numbers of people in the long term. \u00a0But if we can learn which chemical constituents need to be removed and which need to be added, it is possible that a core handful of such factors might be discovered. \u00a0Those that need to be added can be manufactured in bulk by vats of genetically modified <\/span>E coli<\/span><\/i>. \u00a0Those that need to be removed can be targeted with antibodies and removed in a simplified blood filtering procedure. \u00a0This is a promising research path\u2014perhaps the most promising that is visible from where we are now. \u00a0But we\u2019ll never know if it can work until we do an expensive and time-consuming series of experiments.<\/span><\/p>\n
How many transcription factors need to be regulated in order to the job?\u00a0 <\/strong>This is the biggest unknown.\u00a0 When I spoke with Irina Conboy<\/a> four years ago, she was optimistic that the number may be less than ten, but\u00a0last year, she was less optimistic.\u00a0 I take heart from the fact that just four Yamanaka factors<\/a> can turn a differentiated cell into a zero-age stem cell.<\/p>\n
<\/p>\n
Toward the future<\/b><\/p>\n
Plasma transfusions are a safe, approved medical procedure, <\/span>used for decades<\/span><\/a> as treatment for (especially) <\/span>auto-immune diseases<\/span><\/a>. \u00a0No FDA approval would be needed for a clinical trial, using transfusions \u201coff-label\u201d to test rejuvenation potential. \u00a0However this is not a project likely to be picked up by venture capitalists looking to make a quick buck. \u00a0The first reason is that the process will be expensive and time-consuming, with a great deal of trial and error. \u00a0The second reason is that when it is all over, everyone will know what are the best schedules and procedures, and the most important transcription factors in our blood\u2014but it is doubtful that this will be patentable intellectual property, or that the investors would be able to maintain a trade secret. \u00a0What we need is a substantial public investment or a middle-aged billionaire angel investor who is thinking clearly about his own destiny a decade or two down the road.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"
- Which chemical components (proteins and RNAs) from young donors are most effective to be added<\/a> back?<\/span><\/li>\n
- Extensive testing is planned, including telomere age<\/a> and methylation age<\/a> in addition to a full battery of standard blood tests like lipids and inflammation markers.<\/span><\/li>\n