First Fruits of Research with Young Blood Plasma

A recurrent theme on this page is the idea that human aging is driven by a combination of proteins circulating in the blood.  Blood is not just red cells and white cells; there is the blood plasma which contains thousands of dissolved proteins (and RNAs), signal molecules which regulate all aspects of metabolism, on time scales ranging from minutes to decades.  As we get older, the mix of these protein signals changes in ways that are relatively subtle, with less of some proteins and more of others.  It has been pretty well established that the mix of proteins is characteristic of your age.  My bet is that the mix of proteins actually determines your age, in the sense that changing the  blood plasma of an old person to that of a young person will, to a significant degree, transform the metabolism toward a younger state.

The promise of this work came to prominence in parabiosis experiments with mice, beginning about 2005 out of Stanford.  Old mice were surgically paired with young mice, so their circulation was tied together.  The old mice become younger and the young mice became older.  In the intervening years, we have learned that blood plasma (no cells) from young animals has a rejuvenating effect on old animals.

But giving old people frequent transfusions from young donors sounds like an experimental procedure for aging tycoons, not a practical plan for population-wide life extension.  Alternatively, to reproduce the full suite proteins in young blood artificially is a daunting task.  Are all the proteins necessary for rejuvenation, or, perhaps, might the same success can be achieved with just a small number of proteins?   Some would be added, others effectively subtracted from the blood by blocking their receptors with an inhibitor.

So the race is on to find candidates for proteins in the blood that could be part of this small subset, a handful of proteins that might, if we’re lucky, stand in for the thousands whose concentrations change with age.  The Stanford students from 2005 have graduated and now have labs of their own at Berkeley and Harvard  In the last few years, Mike and Irina Conboy of Berkeley identified oxytocin as a key protein, and Amy Wagers at Harvard identified GDF11, both proteins that we lose with age, and concentrations might be beefed up for rejuvenation.  Oxytocin is holding up; there is controversy about GDF11.

But more effective than adding “youth factors” to old blood may be removal of pro-aging factors.  This was the preliminary finding put out by the Conboys a few months ago.  Right around this time, from the lab of Tony Wyss-Coray at Stanford, came the first report of anti-aging benefits from blocking a circulating protein.  VCAM-1 is a protein that increases with age, but has not previously been identified as a bad actor of primary import.  The “CA” in the middle of VCAM stands for cell adhesion, an essential cell function which in itself is not good or bad.  Cells stick together for many reasons.  But VCAM-1 has been loosely linked in the past to cardiovascular disease and to arthritis.

Hanadie Yousef, a post-doc at Wyss-Coray’s Stanford lab, presented preliminary results at a Neuroscience meeting in November, indicating that

  • VCAM-1 increases by only about 30% in blood of the elderly, but this is enough to make a difference.
  • Higher levels of inflammation and lower nerve growth in brains of older mice were linked to VCAM-1
  • An antibody that binds to VCAM-1 and pulls it out of circulation was successfully used to prevent these effects.  Inflammation and nerve growth were both restored to levels typical of young mice.

Of course the findings are preliminary, and yet unpublished [Yousef abstract].  No anti-aging has been demonstrated in normal, living mice, but the benefit of intravenous antibody injections has been demonstrated in mice that are served up artificially with too much VCAM-1, and the molecular mechanism has been validated in cell cultures.

I find it promising that the research is being done on brain function.  The central timekeeper that coordinates change in blood chemistry through a lifetime has not yet been identified, but neuroendocrine regions of the brain are a promising place to look for it.  Human clocks are built on feedback loops, and if evolution’s engineering immitates human arts, then we might look for an epigenetic aging clock based on secretions from the brain that feed back to act indirectly on the brain.

Other blood proteins that increase with age, and which presumably could be targets for antibody therapies include the pro-inflammatory signals NFkB and TGF-ß, also the reproductive hormones LH and FSH.

I believe that the work of these three groups is the best prospect we have for powerful human anti-aging interventions in the medium term.  In the short term, I think that senolytic agents will be the Next Big Thing.  In the long term, we will learn how to reprogram our epigenetics.  For the next decade or two, keep an eye on ciculating blood signals

Three previous posts with background on this subject:

How does the body’s hormonal signaling change with age?
Signal molecules in the blood: what do we have too much as we age?
Signal molecules in the blood: what do we lose with age?

64 thoughts on “First Fruits of Research with Young Blood Plasma

  1. Josh your posts are truly appreciated for timely updates on topics of interest peppered with your own insight on the developments. On the above post I agree fully – the secret lies in the circulating signals and when we upstream: in the genetic instructions that decided which signal proteins to dial up and which to dial down. Identifying these signals is progress from all the earlier research of trying to solve the symptoms of aging. But ultimate cure may come from epigenetic reprogramming. But agree with you this is interesting progress for the interim stage.

  2. Very good Josh this is the same conclusion I have reached and wrote about recently on LEAF. It is more about what you remove than what you add, the dilution effect was obvious to me after I talked to Irina and Michael 2 years ago.

  3. Also Josh CD38 Protein in SASP is another one of these factors and you only have to look at Sinclairs work to see how inflammation and rising levels of CD38 correspond with loss of NAD+

    CD38 destroys NAD and when it is inhibited by Quercetin or Apigenin both common supplements NAD levels return.

    To me everything points at inflammaging and immunosenescence as the root for altered intercellular communication.

  4. If a purported anti-aging treatment doesn’t extend the life span of wild-type heterogeneous mice; it is a hoax. Time for anti-aging medicine to move beyond junk science and snake oil medicine. Rapamycin, metformin, angiotensin II blockers, caloric restriction, physical activity are real anti-aging medicine based on medical facts and scientific research.

  5. When I first published about heterochronic plasma exchange (HPE) it was to describe how different groups found both positive and negative regulators of aging. As oxytocin and BMP11 were positive regulators, so CCL11 was a negative regulator that accumulated in the cerebrospinal fluid and impaired cognition and neurogenesis and suggested that both the removal of age-related, pro-aging molecules and the provision of youth-related anti-aging molecules or conditions would be solved by plasma exchange. This could be made into a solution particularly if this plasma can be stored, but more importantly, it would be a proof-of-concept that would change human history.
    Also I think you are limiting yourself to imagine that it might be blood borne proteins that are the only actors in aging.

  6. Let’s not forget the HUGE decline in some other “good” hormones with age like melatonin, DHEA, pregnenolone, progesterone

    And keep in mind that monkeys undergoing caloric restriction which increases life span had much increased levels of melatonin and DHEA.

    As far as trying to stimulate the Yamanaka factors which actually reversed aging recently in recent experiment, I found that if you inhibit the CD47 protein with some sort of morpholine antisense- it boosts the levels of Yamanka factors!

    • Hi Jeff… Most of my family members have a copy of your Vitamin D3 book… Thanks.

      Do you have a study reference link for the CD47 hypothesis? Thanks

      • Hi Desert Wizard

        Glad you liked the D3 book >>200,000+ copies now sold, hey everyone else-if you hacvent read ti you are missing out on some crazy new stuff! Just go to amazon books type in vitamin d and the book will pop up as #1 by far compared to all the other vit d books…

        Anway havent done much research yet on cd47 inhibition activates Yamanaka factors but here is one study that is a good start>>

        Altmetric: 18Views: 11,468Citations: 33More detail
        Article | OPEN

        Thrombospondin-1 Signaling through CD47 Inhibits Self-renewal by Regulating c-Myc and Other Stem Cell Transcription Factors
        Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein, Chengyu Liu, Abdel G. Elkahloun, Michael L. Pendrak, Alina Nicolae, Satya P. Singh, Zuqin Nie, David Levens, Jeffrey S. Isenberg & David D. Roberts
        Scientific Reports 3, Article number: 1673 (2013)
        Download Citation
        Cell signallingOncogenesSelf-renewalStem-cell research
        11 February 2013
        02 April 2013
        Published online:
        17 April 2013
        Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors.

        CD47 is a signaling receptor for the secreted matricellular protein thrombospondin-1 and the counter-receptor for signal-regulatory protein-α (SIRPα), which on phagocytic cells recognizes CD47

        Le t me and or Josh know what you find out!!! thanks Jeff

  7. January 24, 2017

    Josh M Said: January 23, 2017:
    It has been pretty well established that the mix of proteins is characteristic of your age.

    Avi/Beat Aging Collaborative Discussion & Question: Yes, protein in the circulating blood is certainly is being search using the new tools of Proteomics by leading labs in USA & elsewhere, not so much for “Anti-Aging” but more so to find ways to find therapeutics for diseases, far more so. Of course, “Anti-Aging” and “Diseases” are linked as proven, statistically and medically. Proteomic “Search” are now yielding potential target enzymes & proteins for intervention for such diseases as Alzheimer, Perkinson’s, Stroke, and more !. But if we want to look at this “Proteomics” search from “Aging perspective” we have got to link “enzymes or proteins” in the blood or specialized cells, near the CNS in the brain, find a way to connect what we know about Telemere Shortning to these circulating proteins. Any thoughts on how and where to look based on last 5 years of discovery ?

  8. Removal/reduction of VCAM-1 sounds like an ongoing process.

    In this blog you’ve mentioned feedback loops, and it definitely seems like the body would have many of them, particularly with regard to an evolutionarily important phenotype like aging (ex:circadian clocks).

    I wonder if there would be a way to produce anti-bodies in the gut, or pre-antibodies (a-la Niagen) but with engineered bacteria we could take as a pro-biotic. That would give us 24/7 protection, and the hurdles would be much lower than attempting to edit our own genome.

    • Hi, Donovan –
      Yes, engineering bacteria to produce specific proteins is at this point a mature technology. We know how to do it. And modifying the genomes of living humans is still difficult and risky.
      The former can get proteins into the gut, but they still face barriers of absorption through the intestine wall and into the bloodstream. The latter can get proteins into the cell directly.
      – Josh

  9. Another angle could be creation of chimeras from like mouse and naked mole rat blastocyst. I dont know if it is possible or not, there have been successful attempts on living mouse – rat chimeras. I wonder what lifespan those chimeras would have.

    • Hi,

      Along your line of thinking, would’nt it be interesting if it were possible to create a developmental chimera in which in the hypothalamus or the entire brain was mole rat derived while the rest of the animal was rat derived. It seems to me that this kind of binary experiment would let us know if a primary aging clock is located in the brain?

      • Hi there,

        From Personal communicantions with Dr. Morley os St Louis U-He told me about an experiment he did with Donner C. Denckla-now deceased . Where they bought hypophysiectomized (Spelling??) rats (whcih means their pituitaries were removed)
        and they supplemented them with most of the hormones they knew that were vital like cortisol,etc…but did not give them any GH. And the rats lived a crazy extreme long time p;ast the normal maximum life span. This one experiment was never published, I think Denckla died during it and his widow woudl not give up the data or permission.
        My thought on this , assuming it is all correct, is they might not have given them LH and FSH so this might have been the cause of life extension as opposed to GH deficiency.
        Although the Ames dwarf mice bred to be low in GH are small and live a long time>>so who knows??

        • Hi Jeff,

          Yes, I remember reading about his work back in the 80’s or 90’s, he was ahead of his time.

          Another thought would be to create short/long lived chimeras where the immune system was from say the naked mole rat in a short lived rodent? It seems to me that, if feasible, these kind of studies could answer a lot of questions. This idea would not preclude the role of the brain considering the strong neuro-immune links.

  10. Great post Josh. I’ve recently been thinking and acting around this topic. I’ll share in a few comments.

    First, about a practical way to dilute Old Blood factors –>> Donate whole blood or platelets/plasma at a Red Cross Blood Donation Center.
    “Blood” has 4 major components. Red Blood Cells, White Blood Cells, Platelets, and Plasma. A Red Cross “Whole Blood” donation is a donation of all 4 components and this type of donation can be made every 8 weeks.

    Old Blood Factors circulate in the Plasma. Plasma is mostly water, along with many other things, including old blood factors. There are commercial locations across the US that will pay for plasma donations. Apparently, plasma donations can be made 2 times a week. Despite the creepy feeling, I was seriously thinking about trying it until a couple weeks ago.

    I made my first RC whole blood donation about 4 weeks ago. Then I got a call 2 weeks ago from the RC telling me there is a platelet shortage right now and asking me to donate platelets. My question to the caller: Can I give Plasma along with the Platelets at the same time? The answer: Yes, that’s the way it’s done. Platelets are derived from the bone marrow and live 5 to 9 days (per Wikipedia). I’ll quickly replace what I donate. A Red Cross Platelets/Plasma Donation can be made every two weeks.

    I won’t be getting young blood, but I will be diluting old blood factors.I do my first platelet donation next week I can report back on the experience if that would be interesting.

    Old blood factors can be diluted “at the periphery” of these biological entities we call bodies (i.e., via a needle blood draw), but that’s not the only way they can be diluted. Old blood factors can also be diluted via a mechanism controlled “at the center” via specific neuronal receptors in the brain.

    Pinging those receptors is as important a way to dilute circulatory aging factors as taking a needle in the arm. And the studies showing increased survival odds via the receptor pinging mechanism far outnumber the studies that manipulate the blood directly.

    I’ll post about this second approach, including study links demonstrating its relevance to blood aging factors, in my next comment.

    Steve Buss

    • January 27, 2017

      RE: Steve Buss (HighDesertWizard) 01/27/2017 Comment
      On “First Fruits of Research with Young Blood Plasma ” Topic

      Old blood factors can be diluted “at the periphery” of these biological entities we call bodies (i.e., via a needle blood draw), but that’s not the only way they can be diluted. Old blood factors can also be diluted via a mechanism controlled “at the center” via specific neuronal receptors in the brain.
      Avi/Beat Aging Collaborative Conversation & Question:

      First of all , this is a valuable experience about RC blood donation. I would like to request more clearly in the context of therapeutic value, what is meant by “Specific neuronal receptors in the brain”. in thie context of receiving the Platelets by someone who apparently needs these “platlets” and the “old blood factors”. Wh
      What Therpeutic Benefits to the receiver now? How can the therapeutic benefits strengthened in future via “enhanced value Platelets” with old and new blood factors ?

    • Yes, there is epidemiological evidence to suggest that people who give blood live longer, and there is theory to make it plausible.

      Giving the red cells is potentially therapeutic as well, since most of us have more iron than is good for us.

      • I love the blog. Thanks for taking the time to share your thoughts and research.

        Most males may have surplus Iron in their blood, but most females in their reproductive years do not.

        The lab ranges for Ferretin and other markers are very wide. (Limited) Studies show fatigue reduction in non-anemic patients who undergo iron infusion.

        I had to learn a lot about this due to family member with extreme fatigue. As well, I then found lots of ancedotal evidence ferritin should never fall below 30, and ideally 80. Not a problem for most men, but it is for many women with heavy peroids.

        And in our case all this proved to be true.

  11. My daughter was once on an antibody treatment — infliximab (Remicade), which binds TNF-alpha — to treat an inflammation-related disorder. We got her off it using natural substances like vitamin D and curcumin.

    Last we talked to the doctor, the adult dosage was costing as much as $100K a year, in part due to high profit margin, cost of litigation due to adverse reactions, and the body creating antibodies to the foreign antibodies.

    So I have the view that if an anti-aging treatment involves big pharma and the medical industry, we might as well forget about it. We would be kept alive as serfs.

    • Bill my firm is going into clinical trials to significantly slow down rate of deterioration caused by aging using natural or naturally occurring agents. The problem is even if we are successful it would be very challenging to get any IP protection. Will have to be happy with the satisfaction and the benefits which is not that bad after all. Will keep you posted through Josh’s site. I hope you had success with using curcumin? It should be used either with a lipid in nano form or with black pepper extract to ensure effective bioavailability. There are other natural interventions against inflammation.

      • The curcumin works well. My wife and I take it too, and I notice less tendency toward inflammation issues. We are using the Thorne Research Meriva brand. Thorne has patented the sustained release aspect of it. So there are ways to protect IP..

        • Yes I just checked the brand”s product the phospholipids should help improve absorption. And yes we too are trying to discover novel methodology , conjugates etc and hope we can win patents. But whether we can defend them especially with minor variation by bigger companies we will find out. All the best

      • Hi Akshay… What’s the name of your company and/or what is the url for it? I’m very interested in what you’re doing.

        About 10 years ago, I accidentally cured myself of Carpal Tunnel Syndrome using very large doses of Boswellia [AKBA] (using 5-Loxin).


        • Hi HighDesertWizard,
          Thank you for your interest – we are under the radar so no url yet but I do have a blog where I tried to make an exhaustive compendium of natural therapies against cancer called Atomic Bliss
          Our approach is to identify the main villains that sneak out in large numbers due to fall in the efficiency of repair mechanisms and discover natural or naturally ocurring in vivo agents that either upregulate the repair mechanism or neutralize the villains on a holistic basis. As everything is interrelated, assuming every deterioration we mitigate is a pole, if we raise sufficient poles we hope to lift the entire collapsing tent back up. We are excited because just for discovering a synthetic molecule that cleans senescent cells Unity bio was handed $116 million by the likes of Jeff Bezos. Just one of our natural interventions upregulates/activates autophagy itself which is much safer than just removing senescent cells. Also the key is to meter the intervention as it should mimic the peak youthful levels not more and not less. Indiscriminate interventions using synthetics can end up causing harm (side effects). In this case for example some amount of senescent cells are needed for healing. Plus we also upregulate UPS a process that has not been given equal importance as autophagy in anti aging. Only when both work in sync the appropriate recycling of cells and proteins will occur. We are developing proprietary tools to meter and measure the interventions.
          If you are a scientist and wish to collaborate you can write to me at atomicblissventures at gmail dot com

  12. The question on the table from my last comment is this…
    Do humans have an innate mechanism, directed by a specific set of receptors in the brain, that, when appropriately agonized, diminishes the expression of Old Blood Factors in the circulation?

    I believe the answer to that question is Yes based on science that cannot at this point be falsified.
    — A sketch of a few argument points supporting that belief, along with 1 study link (of many) per argument point, appears below. What is the argument?
    — There is an innate mechanism in humans, directed/controlled by receptors in the brain that can reduce the most often mentioned Old Age Blood Factors, TGF-B1, B2M, and, now, VCAM-1.
    — I won’t describe the mechanism in this comment but will provide links that describe it in my next comment. In Josh’s recent blog post about Chinese Medicine, I provided links to study evidence demonstrating that Acupuncture that provides benefit works through the same receptor types (Muscarinic-Acetylcholine Receptors and a7 Nicotinic-Acetylcholine Receptors) and Vagus Nerve Fibers.

    Old Blood Factors are coincidently related to disease severity in Rheumatoid Arthritis
    — TGF-B1 is implicated in Rheumatoid Arthritis @
    — B2M is implicated in Rheumatoid Arthritis @
    — VCAM-1 is implicated in Rheumatoid Arthritis @

    Vagus Nerve Stimulation attenuates disease severity in Rheumatoid Arthritis @
    Autonomic Dysfunction precedes RA Development @
    Chronic Vagus Stimulation Improves VCAM-1 level @
    Increased Heart Rate Variability (associated with increased Ach) increases survival odds in Humans @

  13. Hi Josh,

    Here is possibly another perspective on the evolutionary significance of VCAM-1

    Selfish, Virally Derived Genes and Aging

    It seems plausible to me that genes that are derived from viruses such as elements of the vertebrate immune system, even those originating deep in the evolutionary past will be selected for based on their ability to recognize (in some fashion) that the host cell is dying. In this event it seems reasonable that these genes will attempt to initiate processes that will lead to their expression as phage particle so that they can escape the dying cell. This process should occur even if they no longer have a complete and intact genetic apparatus with which to implement and complete the process successfully as many genes “decay” very slowly in evolutionary time. If correct, this could explain why we see such unusual patterns of exaggerated gene expression is aged tissues. One way to examine this potentiality is to compare expression rates in aging cells of genes that do not have viral origin with those that do.

    If this idea is correct, then these aberrant gene expression patterns that are characteristic of aging are not causes of aging as some recent theories propose such as the Transposon Theory of Aging suggest. Rather they are a response to a more fundamental aging process that is already proceeding in the cell. Considering that VCAM-1 proteins are immunoglobulins and as a result have a viral origin, their over expression in aging animals may not be a foundational cause of aging in vertebrates but simply be an expression of the action of selfish genes to an already aging environment.

    • I agree with your premise: factors may not be the cause of aging and curtailing them may impair some of their functions which may be needed. Look at the experience of Amy Wagers with GDF-11. Aging may be caused by a more fundamental recycling code embedded in all living things – plants and animals.

      • Seems to me that the important question is whether some Young Factor is Fundamentally Causal or Not. The Young Factors Evidence is slim I think.

        The Adler/Chang 2007 study entitled “Motif module map reveals enforcement of aging by continual NF-κB activity” *, showed that NF-kB expression was The Significant Independent Variable that decreases the odds of Survival. And that’s consistent with a raft of studies showing increased odds of Survival via NF-kB Inhibition.

        Compressed Links…

        • The question is what causes or triggers NF-kB expression. Which epigenetic marks lead to its expression and when. Separately does its inhibition have any unwanted side effects which would need to be studied in the long term. I wonder whether inhibition of one factor or a few factors would be sufficient to stall the overall deterioration caused by aging. Although it remains an intriguing prospect further investigation.

  14. Made progress on the 3rd of 3 interventions I believe we can do now to dilute Old Age Factors in blood. I made a Platelet donation yesterday at a Red Cross location. I’m speculating that a Platelet donation is better than a Whole Blood donation because Platelet donations can be made more frequently (24 times a year).

    It was a great experience. Learned a good deal about how I might do the process better. For my weight, my total blood volume is likely between 6.5 and 7.0 liters. I was told the plasma I rid myself of was about 600 ml. Links to post-draw pics below. The small yellowish and red plastic package contents are platelets and red blood cells. The larger yellowish contents is the drawn plasma. @ and

    Learned that papaya enzyme, Vitamin K2, and Folate increase platelet count.

    As important, I now have an anecdotal report on how well the 1st of the 3 methods works from my own experience.

    About 7/8 months ago, after 4 years of research and posting about it at Longecity, I began taking non-prescription substances to Trigger the Cholinergic Anti-Inflammatory Pathway Mechanism I harangue people (especially Josh and Steve Hill) to take seriously and write about. 🙂 (I posted links showing that this mechanism impacted Old Blood Factors in an up thread comment.)

    Well, I got blood test results back last week, before my RC blood draw, and the results were better than I could have imagined…

    — ESR = 0 (yes, zero)
    — hsCRP = < 0.20
    — Lp(a) = 16.0 mg/dL

    ESR and hsCRP are roughly and positively correlated with B2M and VCAM-1. And I just recently learned that ESR blood tests can be purchased at the Life Extension Foundation for draws at Labcorp so diagnostic progress can be monitored. Current LEF price? $ 22.43 a draw… 🙂

    That last value for Lp(a) confirms that the ESR and hsCRP are not strange anomalies. Background…

    I have CAD and my Lp(a) value has always been high (75 mg/dL to 85 mg/dL) and very problematic. (The reference range is 0 to 30.) Lp(a) has been called the "widow-maker" LDL. 20 years ago, I began doing health science research precisely because the conventional wisdom then was that Lp(a) could not be lowered by diet, exercise, or any known substance. Talk to a cardiologist. Many/most? still believe it cannot easily be lowered.

    The key to understanding why this Lp(a) value is important confirmation… Lp(a) is an "acute phase reactant". A high value, in those with a genetic disposition for Lp(a) expression, means that the Immune System is too "at the ready" to trigger too many inflammatory cytokines. In a 2015 study, IL-6 blockade was shown to profoundly reduce Lp(a) expression.

    And from a 1998 study @

    "In summary, we have identified a calcium-dependent interaction of Lp(a) with HCAEC capable of inducing potent surface expression of VCAM-1 and E-selectin that does not appear to involve any of the known potential Lp(a) binding sites."

    Here's an informal way to describe this 3 fold approach to diluting Old Age Blood Factors…

    1 – Hit 'em High (by pinging receptors in the brain to reduce inflammation in the circulation)
    2 – Hit 'em Low (by establishing a healthy microbiome… Both B2M and VCAM-1 increase when the gut expresses Uremic Toxins)
    3 – Drain the Swamp (by making a Red Cross Blood Donation that includes Plasma)

    A benefit of this approach… It can be done Now!

    Steve Buss

  15. Hot off the press… It begins… The mapping of specific Acupuncture Points to Neuronal Muscarinic-Acetylcholine Receptors in the Brain for triggering activation of the Cholinergic Anti-Infallamtory Pathway (CAP)…

    I need to revise my 3 fold strategy for diluting Aging Blood Factors…

    1 – Hit ’em High (in the brain by pharmacologics or in the hand with a needle)
    2 – Hit ’em Low (via diet and/or probiotics)
    3 – Drain the Swamp (via a Red Cross blood donation)

    Kevin Tracey, in a February 2017 study, provides yet another innovative diagram. Like others he’s published. It depicts organs, cells, neurotransmitters, etc., all in the same diagram.

    The diagrammatic innovation this time is the appearance of a hand to illustrate the location of the “Hegu” acupuncture point at which one might ping brain Muscarinic-Acetylcholine Receptors (mAchRs) to stimulate the Vagus Nerve to agonize a7 Subunit Nicotinic-Acetylcholine Receptors (a7nAchRs) in the Spleen.

    Believe me, I get it… How convoluted and strange is this mechanism? But this artful design for inflammation inhibition was done by none other than the renown artist, Mother Nature. And Josh Mitteldorf once said, in a great talk at a SENS conference… “we’re not smarter than Evolution”. So, I guess accepting and understanding this design might be part of the mission for Longevity Science Enthusiasts.

    Here’s a link to the diagram… @

    Here’s a link to the study abstrat @

    Full PDF available at you know where…

    Why is this important?

    Because the CAP is a lot about inhibiting NF-kB Inflammatory Cytokine Transcription in Splenic Macrophages… And doing that results in profound increases in Survival Probability Odds… That’s “the beef”, right?

    Survival Probability Odds Curves here @

    Hmm… What might we call this mechanism?

    How about this? The Splenic Macrophage Inflammation Limitation Explanation of Longevity…

    It’s The SMILE of Longevity…

    HDW (aka, Steve Buss)

    • A Response to Adrian’s Reference on New Scientist
      News & Technology
      22 March 2017
      Old blood can be made young again and it might fight ageing

      Discussion: osteopontin surprising in rejuvenation of aged is certainly cause for optimism at this early stage of clinical. While Hartmut Geiger at the University of Ulm in Germany is focusing on developing a medical intervention from his discovery, much unknown remains about permanency of the effect of Osteopontin. For example, it would be wonderful, if a bright young clinical scientist would take on the challenge of examining the effect of Oseopontin on a well known marker such as Telemeres. Does this effect lengthens or shortens Telemeres ? Or no effect ? who will step forward to answer this question ?

        • We are doing large pre-clinical study divided into 3 protocols: 1. Heterochronic involves young plasma, young whole blood and young exosomes. 2. A proprietary cocktail of natural and endogenous molecules and compounds to upregulate major repair pathways. 3. Combination of the above.
          Earliest we can expect to submit for publication would be in March/April.
          P One are you from research?

          • So what you describe is not the plasmapheresis approach. What the Conboy’s are proposing is that something in old blood ages the animal, and plasmapheresis is an attempt to take down levels of all of the immunoproteins, on the hope that one or more of those (still to be identified) proteins is what is causing aging.

            The Conboys already did a plasma exchange experiment, and old blood hurt the young animals more than young blood helped the old animals. That result suggests that something in the old blood needs to be removed or diluted.

            I am not a researcher. I am watching the plasmapheresis experiments with great interest because the FDA approvals already in place for plasmapheresis suggest to me a way that this could become a widespread treatment rapidly, once efficacy is shown.

            Later, once specific proteins are identified in old blood, this would change to an immunoadsorption approach, which would carry far fewer side effects because no exchange fluids from human donors would be required. Only specific proteins in aged blood would be removed.

          • Our young plasma experiments involve plasmapheresis. Heterochronic – young to old – it can involve other media. Our CTO communicates with Michael Conboy – Michael thinks highly of him. Hope you have seen Alkahest results. So far results in animals have been mixed in all the published studies. Finding factors in plasma too has not shown replicable success so far – to note is GDF11 by Amy Wagers.

          • If the study involves going from young to old, then by definition it is not a test of the latest Conboy hypothesis. The latest Conboy hypothesis is that there is something in old blood that needs to be removed, and the proposal is to use plasmapheresis – without any young animals – to do that removal.

            Conboy predicted Alkahest would fail, and conceptually the Alkahest approach is not in line with the Conboy’s latest proposal.

            GDF11 is an example of an attempt to find a miracle protein in young blood that would make old animals young, which again is something that is the opposite of what the Conboys are suggesting might be happening.

            I just want to see the Conboy’s latest idea get a real test.

          • The problem with that theory is they have been doing plasmapheresis on humans under FDA approval for decades now. There are studies showing all of the side effects in more than 10K procedures done. So plasmapheresis on its own seems more safe than not.

          • The plasmapheresis procedure being conducted from decades approved by FDA works like a donation of plasma which then is infused into patient. Whereas here we are talking about removing one or more factors identified as cause of aging in old blood completely or a high percentage above 90% to stop it’s detrimental action in aging humans. Just using plasmapheresis to implement this but different from plasmapheresis done to donate plasma.

          • Hi Akshay, P One,

            Did you ever read this?

            ‘Protein profiling reveals consequences of lifestyle choices on predicted biological aging’.

            Surprisingly the largest benefit came from drinking coffee and this jives well with the hypothesis it is inflammatory factors in the blood causing the issues, supported by papers such as the this coming out of Stanford;

            ‘Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states’.

            If I had to speculate, I’d say the body is trying to ramp up stem cells (unsuccessfully) and this is why inflammation rises so much in the elderly, and this is part of what is causing the harm to young subjects who take old blood. Just my opinion.

          • Mark yes inflammation is a common thread amongst most of the fabric of age related diseases but inflammation is a result of other upstream dysfunctions. We can look forward to new therapeutics which resolve and normalize inflammation. It would be quite exciting to see it’s over all impact on aging.

          • Yes Mark will surely – share good or bad. You seem to have acquired very good knowledge on aging. If you have any ideas that won’t take too much funding to test then may be we could try. Alan, Harold, Paul, Josh all are putting their knowledge to some translational excercise. I thought you too deserve to do that at some point. If anyone of us succeeds it benefits everyone.

          • Thanks Akshay, I’ll give it some thought. I have built my understanding based on reading a large number of papers on aging as a hobby, I don’t actually do the work like you do, although often I wish I did.

            What seems instructive to me at present is that when a young person has an injury you get senescent cells and a spike in inflammation, particularly IL-6, which spurs regeneration, and then inflammation is resolved fairly quickly. In the old inflammation seems to be higher generally, but unable to respond to a chronic need. You see a similar thing with the anti-oxidant response pathway – always turned on (unlike the young), but unable to respond to a immediate need. One thing I am certain of, resolving inflammation will not be enough, we’ll need to somehow restore youthful gene expression too, whether this is through telomeres or new/restored stem cells, etc.

          • BTW I too am not a academic or a scientist by profession – like you a passionate researcher. I raised funding to translate some compelling aging science and ideas to see if it can lead to therapies that can prevent suffering of age related maladies. Gerald de Haan Scientific Director, Group Leader of the Laboratory of Ageing Biology and Stem Cells at European Research Institute of Biology of Ageing discovered in one of their studies that over expression of telomerase in stem cells of mice did not lead to increase in their lifespan. I am with you on reversing epigenetic marks related to aging. An individual example: administration of a cardiac glycoside Proscillaridin A reversed the age related silencing of Tumor Suppressor Genes. As you know even the young constantly have cancer causing mutations every day but one of the potent mechanisms to suppress that is TSG. As we age they seem to be progressively silences due to methylation if their promoter. Due to Proscillaridin A now we know that this epigenetic change caused by aging can be reversed and thereby bringing back up our protection against cancer.

          • That is a fascinating find Akshay. Maybe if you suppressed Cancer for mice and then helped their stem cells with telomerase they would then show the benefits (given most die of cancer)? But I expect stem cells are affected by epigenetic changes independent of telomere length that render them less useful as stem cells.

          • I’m sure you have an amazing story Akshay how you got into this field. And you raised the money too! Pretty damn impressive.

  16. Certainly high inflammation is a marker for many diseases of aging, but aging is much more than just this. A marker for aging is a whole set of immunosenescent changes such as the fall in naive CD8 T cells, which increases the CD4:CD8 ratio. If you ask most 60-year-old persons with very low inflammation markers if they feel like they did when they were 30, I am sure you will get a long list of denials.

    What the Conboys are doing holds out a promise of developing a therapy within 10 years that will make 60-year-old people feel decades younger. Maybe you won’t feel 30, but the 60-year-old might feel like they did at 45. The Conboys are trying isolate one or more proteins that are potentially primary causes of the aging process at a chemical level and remove those from the body.

    It’s a very big idea. It deserves funding and a very thorough examination.

    • I totally agree that aging is more than just inflammation and that this is because there are upstream causes of this elevated inflammation – but as I indicated above, I believe this is because the body is using higher inflammation to try and spur rejuvenation via stem cell differentiation. We had a whole discussion on this under the ‘Varieties of Aging in Nature’ post and it looks likely from the papers we reviewed that Stem Cells are becoming less able to proliferate as we age (possibly due to epigenetic drift into somatic cells), and this combined with somatic exhaustion (short telomeres) causes the problems you see. So yes, an older person who has stopped the rise in inflammation will still not feel young because they still can’t rejuvenate their tissues via stem cells (or not very much), but at least they will not be dying so quickly via inflammation. For stem cell rejuvenation you’d need some other sort of signals – and that sounds like something that would be found in young blood, but not in old – or perhaps blocked in old persons. So not sure whether the Conboy’s proposal would be able to find that or not.

      • I will agree that an older person with low inflammation is at least not rapidly bringing on diseases associated with high inflammation.

        That said, I know too many people over 50 who have virtually zero measurable inflammation, who feel their aging quite profoundly. So inflammation is not a likely cause of aging. It is a symptom of it, in some subset of aging individuals.

        The Conboys are suggesting that stem cells in older people work well but are being blocked by *something*. Their plasmapheresis experiment is trying to prove that by removing most immunoproteins you remove that “something” and thereby renew stem cell activity. It will be up to additional studies to find what those “somethings” actually are.

        • I am not sure that everyone over 50 without abnormal inflammatory factors feels their age profoundly.

          I think most people over 50 begin aging rapidly, but only because they engage in, either none, or very few, known measures to slow the aging process.

          Very few people exercise regularly, take nutrients or drugs, now believed to slow aging, or eat a proper diet.

          I am amazed at how people abuse their bodies.

          • Heather, how did you translate “I know too many people over 50 who have virtually zero measurable inflammation, who feel their aging quite profoundly” to “everyone”? I did not say everyone or imply it. There are always outliers.

            Exercise is extremely helpful when aging, but I think these are not practices that slow the aging process. These are practices to improve your health profile as you age.

            There are no practices that increase maximum human lifespan. You can increase the median age at which animals die, but you do this by improving their health and not by slowing the aging process.

            That said, most of the health practices people follow – except for exercise and eating vegetables and fruits – do very little. People want to desperately believe they can make themselves age slower, but the research doesn’t support 95% of the pill-popping that goes on.

Leave a Reply

Your email address will not be published. Required fields are marked *