(Blood-Plasma-wiki) - (Last Revision Date: 06/27/2024)
◉ Preface
Sherlock Holmes famously stated, “There’s nothing more deceptive than an obvious fact.” This seems particularly relevant when considering the potential of young plasma to rejuvenate older individuals.
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[2018] A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV- A cohort study
To illustrate the point, consider the prevalence of age-related diseases between a group of twenty-year-olds and a group of seventy-year-olds, as depicted in the graphic on the right. This graphic presents the overall disease counts stratified by age from a large dataset. The stark disparity is evident and becomes an "obvious fact" to even the most casual observer. What defines the biological difference between these age groups? It is the signaling milieu contained within the plasma, which indicates and directs the biological age of these two distinct demographic groups.
Recent research underscores the important role of plasma in regulating aging through its rich composition of proteins, growth factors, and signaling molecules. Studies such as heterochronic parabiosis, where the circulatory systems of young and old mice are joined, demonstrate that young plasma can reverse signs of aging and enhance cognitive functions in older mice, while older plasma appears to accelerate aging in younger counterparts. Key components like GDF11, Klotho, and exosomes have been pinpointed as vital anti-aging agents within young blood, shown to boost muscle regeneration and neurogenesis. Human clinical trials further expand on these findings, indicating that young plasma can effectively rejuvenate aged tissues by transmitting youthful signals across all biological systems, potentially revitalizing various organs and tissues. This highlights not only the complex interplay of these signaling molecules in aging but also their significant potential in age-regression therapies. [22]
Resetting the signaling environment controlling the aging protocols set point will not turn an old-individual into a young one; instead, it will regress their biological age to a point that is relatively younger. Research has demonstrated that by diluting the signaling signature in an old individual’s plasma and reintroducing young signals; healthspan (the period of life with an absance of disease), lifespan and quality of life can all be positively impacted. This includes ameraliation and prevention of diseases associated with aging (see graphic below), improved: energy, sleep, memory/cognition, muscle/tissue regeneration, cardio/vascular and sensory functions.
To truly appreciate the complexity of aging and the challenge of reversing it, we must recognize that the biological systems within our bodies operate through a finely tuned orchestration of multiple signals and interactions. This system does not operate merely at a molecular/chemical level but integrates quantum physics, chemical interactions, and electrical signaling. This multifactorial process influences thousands of molecular pathways that then each impose a level of influence on all of the others. This understanding casts a shadow over strategies that rely solely on single-molecule interventions inittially identified and isolated in young plasma to regress aging.
The biological complexity of our systems can be likened to the intricate networks within a computer, which rely on a vast array of transistors and circuits to function. Just as upgrading a single type of transistor would not significantly boost a computer's overall performance, introducing a single molecule from plasma is unlikely to produce lasting or systemic benefits in the biological "computer," that controls aging.
The potential for effective age-regression likely lies in a more holistic approach that respects and utilizes the full spectrum of biological signals inherent in young plasma.
Although this website details many research programs that are attempting to effectively reverse aging, at this point in time, only one is available. Plasma was approved by the FDA for human use in 1938. Rescources to access this safe and effective aging intervention are descrived below.
◉ Introduction
“The hallmark of aging is the decline of regenerative properties in most tissues, partially attributed to impaired function of stem and progenitor cells. In the long history of parabiosis experiments, (conjoining circulatory systems of two animals, one old and one young, detailed below) it was elegantly shown that factors derived from the young systemic environment are able to activate molecular signaling pathways in hepatic, muscle or neural stem cells of the old parabiont leading to increased tissue regeneration.” [9]
Additional studies have demonstrated that the benefits derived from parabiosis were in fact from the plasma of the younger paired animal. [6][25] Plasma, the liquid component of blood that contains water, salts, enzymes, antibodies, and other proteins, has played a crucial role in medical treatments since its first therapeutic use on the battlefields of World War I. This early use demonstrated plasma's vital role in treating shock and blood loss among soldiers. Recognized for its life-saving properties, the U.S. Food and Drug Administration (FDA) approved plasma as a therapeutic product in 1938, enabling its broader use in treating conditions like clotting deficiencies, immune disorders, some genetic deficiencies. This list of therapeutic indications now includes aging. In the words of David Sinclair of Harvard Medical “When you effectively treat aging, the diseases of aging disappear, because aging causes those diseases.”
Young Plasma, normally provided and referred to as young Fresh Frozen Plasma (yFFP), contains all the age signaling molecules, (chronokines) required to shift the epigenetic and biological set point of an older individual to that of a younger one.
Young plasma holds many advantages that no other age-regressive treatment currently in research or clinical development can claim: 1) It’s safe, having been administered to hundreds of thousands of individuals; 2) As the following sections on this page demonstrate from historical, scientific, and clinical perspectives, young fresh frozen plasma (yFFP) is an effective age regression modality capable of increasing healthspan and lifespan; and finally 3) It's FDA-approved and available now.
A non-profit dedicated to promoting the benefits of yFFP; Golden Gift has mounted an excellent website at YoungPlasmaStudy.Com. The website is an informative resource produced by Dian Ginsberg MD who’s videos you can view below.
This webpage provides an introduction and scientific rational for utilizing young plasma as an available therapeutic that is capable of disease prevention, ameraliationa and extending life. It is divided into the following section:
1) Introduction by the lead scientist of Alkahest, a biotech wholly owned by the Spanish giant Grifols, the third largest plasma processing company in the world.
2) Regulatory Control of Aging by Plasma
The Scientific Rational and Mechanism of Action of Young Plasma and its interface with the Chrono-Epigenetic Regulation System (CERS).
3) History of Heterochronic parabiosis and the discovery of aging plasticity.
4) Human Clinical results of yFFP in a wide number of indications including aging.
5) First person experiences with Young Plasma.
6) Videos
7) References.
8) Definitions of Terms Utilized on this Page
9) Companies Developing Plasma or Plasma Derived Therapies
◉ By watching these two videos you will get a quick and comprehensive understand of the benefits of young plasma.
1) TED Talk: Therapeutic Potential of Young Plasma
This engaging 13-minute TED Talk from 2015, delivered by Tony Wyss-Coray, offers a clear and accessible introduction to the therapeutic potential of young plasma. His foundational insights not only enhance your understanding, but also solidify the credibility of the age regression concepts further explored on this page. Since this presentation, extensive research has continued to support the age-regressive benefits identified, with no studies contradicting these findings. The growing volume of research and clinical results consistently highlight the promise of young plasma therapy.
2) Dr Ginsberg’s Presentation at RADDfest
Dr Ginsberg provides a physicians huministic perspective of the safety and effeacy of Young Plasma. If you want a quick, comprehensive overview from a great educator, watch this video.
◉ Regulatory Control of Aging by Plasma
Chrono-Epigenetic Regulation System (CERS)
Building on Wyss-Coray’s introduction, the next few sections provide a deeper examination of the psychological and biological processes that enable young plasma to rejuvenate older organisms, extending healthspan and lifespan.
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The Chrono-Epigenetic Regulation System depicted above and described below provides a simplified overview that encapsulates several critical aspects of the complex and dynamic regulatory processes governing human physiological and aging control. The aging process is fundamentally encoded in the epigenetic state of our cells and is intricately communicated across the body through hormones and other signaling molecules in the blood. Notably, many of these molecules double as transcription factors, providing a feedback mechanism that can influence the epigenetic states of cells far and wide. This dynamic interaction presents a compelling basis for optimism: by fostering a youthful milieu in the bloodstream, we can potentially achieve enduring rejuvenation. This is not just a theory—it's a promising gateway to turning back the biological clock that is being validated in multiple laboratories throughout the world.
CERS exists in three didtinct layers controlling development, immunity, and aging. These layers consists of:
(1) Chronokines Layer: Positioned as the uppermost layer, chronokines function as both sensory and command systems. These molecules, expressed by cells, are crucial in signaling the age state of an organism and often serve additional core functions beyond age signaling. This layer acts as an interface, orchestrating responses based on the organism's internal and external environmental cues;
(2) Epigenetic Layer: Directed by the chronokine signals, this middle layer modulates gene expression through epigenetic modifications such as methylation. By adding or removing methyl groups, it controls access to the underlying genetic material, effectively turning genes on or off in response to chronological (Layer 1) signaling;
(3) DNA Layer: The fundamental layer consists of DNA, which contains the genetic blueprint of the organism. While it remains static in its sequence, its expression is dynamically regulated by the above layers, particularly the (2) epigenetic modifications directed by (1) chronokine activity.
◉ Interaction and feedback between the chronokines layers
The interaction between the these layers can be considers an integral and sensitive feedback loop (see graphic above) that are pivotal in the regulation of physiological processes, particularly in how an organism ages and responds to environmental factors.
From Chronokines to Epigenetics: Chronokines, as signaling molecules, monitor and respond to both external environmental factors and the internal biological state of the organism. When these molecules identify changes, such as those related to aging or circadian rhythms, they initiate signaling cascades that influence the epigenetic layer. This involves the regulation of gene expression through epigenetic mechanisms such as methylation.
Epigenetic Modifications and Feedback: The epigenetic layer modifies the DNA structure without altering the nucleotide sequence. By adding or removing methyl groups, it can expose or conceal specific genes from the cellular machinery, thus enabling or repressing their transcription. This modification is a direct response to the signals received from the chronokines layer.
Feedback to Chronokines: The changes in gene expression resulting from epigenetic modifications can subsequently influence the production and activity of chronokines themselves, creating a feedback loop. For example, if certain genes that influence the synthesis of chronokines are activated or repressed, it can alter the production and release of these molecules, thereby adjusting the organism's response to its environment and aging processes.
◉ Effect of Young Plasma on CERS
The infusion of young plasma into the Chrono-Epigenetic Regulation System (CERS) of an aged organism showcases a sophisticated approach to mitigating aging effects. This process effectively interconnects and remodels the chronological, epigenetic, and genetic layers, allowing the organism to adapt to changes and maintain homeostasis. The dynamic flow of information between molecular/cellular signaling and epigenetic/genetic control mechanisms ensures a responsive regulatory system. Moreover, these interactions redirect the production of new chronokines, creating a feedback loop that not only adapts but also redefines the organism's homeostatic state to reflect a younger biological age. Young plasma stands out as the sole treatment modality capable of comprehensively and effectively rejuvenating each layer in the CERS, promoting systemic health and vitality by steering the organism towards a healthier, more youthful state.
It is important to recognize that a single drug or biological molecule, can't comprehensively reset cellular chrono-epigenetic regulatory systems (CERS) any more than replacing a spark plug can rejuvenate an entire car. True rejuvenation requires re-introducing comprehensive systemic signals, like those found in young plasma, to fully reset the system and return CERS and the organism it resides within to a younger biological age.
◉ The Rational for Young Plasma as an Anti-Aging Intervention
A large number of age regressive treatment modalities are currently in development. Most hold the promise of partial rejuvenation, defined by the reduction of epigenetic clocks, improved physical/biometric outcomes and increased healthspan and lifespans. None of these promising modalities are currently available with the exception of one; Young Plasma.
Young plasma is the source from which many therapeutic modalities are being derived, with each modality essentially acting as a derivative containing a single signaling source. A large subset of the treatments currently in development are individually isolated plasma fractions, as indicated in table-1 below. This fact emphasizes the complexity and compound nature of signals required to effectively regress the aging process. Young plasma contains all of the thousands of signaling molecules, proteins, lipids, growth factors, hormones, and exosomes previously identified as having youthful or anti-aging properties, underscoring the necessity of a broad and multifaceted approach to manipulate cellular chrono-epigenetic regulation systems (CERS) for effective rejuvenation.
Tony Wyss-Coray’s group previously identified 529 proteins that had been reported by multiple studies derived from 4263 healthy individuals with an age range of 18–95 years. These proteins changed their expression level with age in human plasma [ XX2 ] . A literature search revealed that at least 64 of these 529 proteins are capable of regulating life span in an animal models. They also determined that: 75.84% (361) of all proteins associated with aging (529 total targeted proteins) increased expression with age while only 24.16% (115) are associated with a decreased expression. Wyss-Coray has referred to these age signaling molecules as Chronokines. Chrono indicating time and kines indicating signaling.
Importantely young plasma is rich in multiple youthful chronokines signaling molecules—proteins, lipids, growth factors, hormones, and exosomes—all recognized for their anti-aging properties. This rich composition has shown promising therapeutic potential when administered to older individuals, significantly reducing markers of biological and epigenetic aging while enhancing cognitive function and tissue repair. Grifols, one of several giant plasma processing companies, leverages these insights through it wholly own biotech subsidiary; Alkahest. Alkahest development focus is on isolating and developing sterilized plasma fractions (individual molecules isolated from plasma) that target aging and disease. For the reasons previously described the therapeutic benefit from these single molecules is unlikely to create the long term, systemic aging benefits of young plasma.
The interaction between the youthful and aging chronokines represents a complex but never less, numerical war: each youthful signal works to cancel or neutralize the effects of “old” aging signals. As the CERS introduction to this page indicates, it is not this direct, but the analogy still holds. This dynamic can be likened to a battle between two armies: the detrimental aging signals from old plasma, like an advancing force of decline, can be counteracted by the youthful signals from young plasma, which marshal forces of regeneration and repair to reclaim lost ground in the ongoing war against aging. The location of the front line as measured by epigenetic and proteomic clocks plays a critical role in determining the overall health and aging trajectory of an organism. As you age, aging signaling chronokines increase. This makes diluting the plasma a partial, but incomplete interventional strategy. Increasing the youthful signaling chronokines by infusing young plasma provides younger, healthier troops to enter this battle leading to providing numerical superiority on the battlefield of these warring chronokines.
The table of signaling molecules provided below is a very small, generic list of a very large inventory of age controlling signaling agents found within plasma. For a detailed proteomic inventory see references: [13] and The 2023 Report on the Human Proteome from the HUPO Human Proteome Project. The Human Proteome Project Organization maintains a website that provides the results of research designed to identify all of the proteins involved in development, diseases, immunity and aging. They have also produced the excellent introductory video (embedded above) describing proteomics.
Table-1
Partial Inventory of the Molecular and Signaling Components of Human Plasma
1. Proteins:
- Albumin: Maintains oncotic pressure and transports substances.
- Globulins: Includes immunoglobulins, transport proteins, and clotting factors.
- Fibrinogen: Essential for blood clotting.
2. Electrolytes:
- Sodium (Na+), Potassium (K+), Chloride (Cl-), Calcium (Ca2+), Magnesium (Mg2+): Regulate osmotic balance and nerve/muscle function.
3. Nutrients:
- Glucose: Primary energy source.
- Amino Acids: Building blocks of proteins.
- Lipids: Including cholesterol and triglycerides.
4. Hormones:
- Insulin, Glucagon, Cortisol, Thyroid Hormones, Sex Specific Hormones: Regulate metabolism, growth, and reproduction.
5. Growth Factors:
- Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF), Transforming Growth Factor-Beta (TGF-β), Insulin-like Growth Factors (IGFs), Vascular Endothelial Growth Factor (VEGF): Regulate cell growth, proliferation, differentiation, and survival.
6. Waste Products:
- Urea, Creatinine, Bilirubin: Byproducts of metabolism, excreted by kidneys/liver.
7. Gases:
- Oxygen (O2), Carbon Dioxide (CO2), Nitric Oxide (NO): Transported and exchanged in blood, with nitric oxide playing a key role in vasodilation and cardiovascular regulation.
8. Extracellular Vesicles:
- Exosomes, Microvesicles: Membrane-bound vesicles released by cells, containing various biomolecules such as proteins, lipids, and nucleic acids. Exosomes play roles in intercellular communication, immune regulation, and disease pathogenesis.
9. Other Components:
- Enzymes and Coenzymes: Catalyze biochemical reactions.
- Cytokines: Regulatory proteins involved in immune responses.
- Vitamins and Minerals: Essential micronutrients.
10. Water 90% by volume
For a much more complete overview of the proteome of human plasma see:
Additional, therapeutic age-regressive modalities exist and they include dilution utilizing therapeutic plasma exchange (TPE). Some dilution naturally occurs as a consequence of infusing young plasma and TPE can be an additive process when combine with young plasma. If as indicated in the Wyss-Cory paper above, three times as many age associated/controlling components of the proteome increase (75%) as aging progresses and (25%) decrease, it would be a reasonable conclusion that a protocol incorporating a 50% dilution of all plasma proteins, would result in a net positive impact on aging and correspondingly disease. [23] It would appear obvious that modulating the increasing signals to a lower level and increasing the declining signals to a higher percentage would be an effective interventional stratgie. One study by the Conboys demonstrated the benefits of this type of intervention. [11]
Reprogramming induced rejuvenation utilizes transcription factors to alter the epigenetic landscape and may be the most effective age regressive therapeutic in development, but it is still in development and not likely to become clinically or commercially available for 3 to 5 years.
Exosomes derived from young animals like pigs, are in developed by Harold Katcher and others, also appear to be highly effective at reducing epigenetic clocks. Exosomes are a single type of Extracellular vesicles (EVs), found in plasma and as such are also another component of yFFP. One note about exosomes is they are expressed by multiple cell types throughout the body and as their sources are diverse so are the signaling molecules and mRNA’s that get encapsulated in the bi-lipid envelopes.
◉ History of Heterochronic parabiosis and the discovery of aging plasticity
From Myth to Modern Science:
Discovering the Rejuvenating Power of Young Blood
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Throughout history, the quest for immortality has been a persistent theme in human culture, often intertwined with the mystical allure of young blood. Ancient civilizations (circa 3000 BCE - 476 CE) revered blood, especially from the young, for its supposed life-giving properties. This concept found its way into various cultures and epochs, most notably through the enduring legends of vampires. From ancient times to the present, these tales depicted immortality achieved through blood consumption, reflecting humanity's deep-seated fascination with and fear of mortality.
During the Medieval and Renaissance periods (circa 476 - 17th century), this fascination took a more practical turn. Alchemists and early physicians speculated on the restorative properties of blood, a pursuit that mirrored the broader search for the elixir of life. Although steeped in mysticism and often lacking empirical evidence, these early explorations hinted at a profound truth that modern science is only now beginning to uncover.
In an ironic twist of fate, contemporary scientific research has started to validate what these ancient myths and practices have long suggested. Studies in parabiosis, particularly involving the circulatory systems of young and old mice, have revealed that factors present in young blood can indeed rejuvenate older organisms. This groundbreaking research suggests that certain elements in young blood , primarily exosomes at this juncture, have the potential to reverse or slow down some aspects of the aging process.
This convergence of myth and science is a remarkable testament to the intuitive understanding of our ancestors. It underscores a fascinating aspect of human knowledge: myths, often dismissed as mere fabrications, can unexpectedly contain kernels of valid scientific truth. In the case of the rejuvenating power of young blood, a concept once shrouded in legend and mystique, we find a striking example of how ancient beliefs and modern scientific discoveries can align, revealing insights that have been both fostered and discounted for centuries.
Parabiosis: The first Clues to Aging Plasticity
Humanity's enduring quest to conquer diseases, slow or reverse aging, and evade death has led to significant scientific breakthroughs. A notable milestone was achieved over a century ago with the introduction of heterochronic parabiosis, a novel technique that combines the vascular systems of young and old animals. (see illustration on right).
The first recorded experiment of parabiosis dates back to 1864 by the French physiologist Paul Bert. Bert's doctoral thesis, in which he described the concept of combining the vascular systems of two animals: titled "Sur la Greffe Animale." In this thesis, Bert detailed his experiments on albino rats, where he sutured the skin of two rats at their flanks and observed that intravenously administered fluids passed from the circulation of one animal into the bloodstream of its attached partner. [1]
Source: [2014] A Revival of Parabiosis in Biomedical Research
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A pioneering parabiosis study by Clive McCay at Cornell University in 1957 [2], joined the circulatory systems of young and old rats, providing early evidence of the rejuvenating potential of young blood, observed through improvements in cartilage health and other age-related conditions in older rats. In 1972, Ludwig and Elashoff, at the University of California studied the lifespans of old, young rat pairs. Older partners conjoined to young rats lived for four to five months longer than controls, suggesting for the first time that the circulation of young blood might affect longevity.[3] This provided the first documented study resulting in the extension of life in an old animal as a result of exposure to a young animals blood.
In 2005, researchers Irena Conboy and Thomas Rando reinvigorated interest in parabiosis, exploring in greater depth the molecular and cellular mechanisms through which young blood might rejuvenate older organisms and its potential implications for human aging and age-related diseases.[4] This ignited a quest to identify exactly what the signaling molecules were within the blood that imparted the age regression benefits.
Heterochronic parabiosis has been instrumental in uncovering many of the secrets of aging. It disclosed the potential of young mammals' plasma, which contains age signaling molecules. Youthful signals are referred to here a Type 1 Chronokine Profiles (T1CP). Aged or old signals are identified as Type 2 Chronokine Profiles (T2CP). The levels of each age-defining molecule present in the plasma of younger organisms, capable of imparting anti-aging effects when introduced in sufficient quantities into older animals, essentially represent a youthful biochemical signature that defines and aligns the cells of the older organism to the same approximate age as the donor.
Parabiotic studies are continuing to demonstrate multiple benefits of pairing young and old animals, particularly overloading the system with youthful, T1CP signals, overridingand/or suppressing T2CP aging signals. [13] These benefits include enhanced muscle and tissue regeneration, mirroring younger counterparts, marked by epigenetic clock alterations. Cognitive functions, including memory and learning, improve, while signs of cardiac aging, such as heart hypertrophy, are reduced. Liver function is notably better, and stem cell revitalization occurs, aiding in tissue maintenance and repair. There's a significant reduction in age-related biomarkers, suggesting a systemic reversal of aging, including dramatic reductions in multiple epigenetic clocks. Additionally, age-related diseases, including degenerative conditions, show signs of alleviation or resolution. Finally, an increase in lifespan has been observed in older animals, attributed to the rejuvenating effects of young blood.
As we indicated, these studies are continuing today with the most recent one [Biological Age Reduction and Lifespan Extension Upon Youthful Circulation Exposure; Zang et al., 2023] demonstrating that the two most effective age-regression targets: epigenetic and transcriptome remodeling, are both modulated in a positive way resulting in the extension of lifespan and health'span.
Another important insight was again accomplished by the Conboy’s when they demonstrated that simply diluting the plasma of older (T2CP) animals with sterile saline provided significant benefits in multiple tissue types, improved memory and cognition and reduced inflammation. This suggests that a mere reduction in the T2CP signals is sufficient to improve the health of an individual. An approved medical procedure, therapeutic plasma exchange or plasmapheresis is currently available to achieve this type of plasma dilution. A large human clinical trial is currently being conducted by Dobri D. Kiprov, MD HP (ASCP) In collaboration with Irena Conboy’s group to determine the impact on aging and disease from the dilution of the plasma by plasmapheresis.[16]
In 2020 it was determined by Harold Katcher [19] that fractions within the plasma as opposed to the blood cells contained the molecular signaling agents responsible for these biological, age signaling benefits. Although identified in his first patent [31], it was not until a 2023 publication that the active molecules imparting age regressive benefits were definitively identified as a specific subtype of extracellular vesicles; exosomes.[36].
◉ Human Clinical results of yFFP in a wide number of indications including aging
This section also include recent and relevant research for each disease indication.
( This section is constantely being updated )
By Disease Indication:
Young plasma transfusion has been explored in various clinical contexts, primarily targeting age-related diseases.
Review Articles of Young Plasma in addressing Age-related diseases
[2023] Aging and age-related diseases with a focus on therapeutic potentials of young blood/plasma
Aging is accompanied by alterations in the body with time-related to decline of physiological integrity and functionality process, responsible for increasing diseases and vulnerability to death. Several ages associated with biomarkers were observed in red blood cells, and consequently plasma proteins have a critical rejuvenating role in the aging process and age-related disorders. Advanced age is a risk factor for a broad spectrum of diseases and disorders such as cardiovascular diseases, musculoskeletal disorders and liver, chronic kidney disease, neurodegenerative diseases, and cancer because of loss of regenerative capacity, correlated to reduced systemic factors and raise of pro-inflammatory cytokines. Most studies have shown that systemic factors in young blood/plasma can strongly protect against age-related diseases in various tissues by restoring autophagy, increasing neurogenesis, and reducing oxidative stress, inflammation, and apoptosis. Here, we focus on the current advances in using young plasma or blood to combat aging and age-related diseases and summarize the experimental and clinical evidence supporting this approach. Based on reports, young plasma or blood is new a therapeutic approach to aging and age-associated diseases.
[2019] Blood-Based Therapies to Combat Aging
An emerging approach takes advantage of molecules circulating in the blood to limit or reverse aspects of aging in various organs throughout the body. Efforts are underway to translate these findings into novel therapeutics that harness the activity of youth-associated molecules present within blood. Here, we discuss the current state of blood-based approaches in this arena. Despite the apparent ease with which blood products might conceivably be applied as treatment paradigms, we propose that challenges nonetheless exist, which may be overcome with mechanistic studies that identify common pathways for targeted therapeutics.
Arthritis (Degenerative )(Knee pain)
Alzheimer’s Disease (AD)
Alkahest, a biotechnology company, conducted several clinical trials using plasma fractions from young donors to treat Alzheimer's disease. Early phase trials suggested some improvements in biomarkers and cognitive function, but results were preliminary and required further validation.
A small trial at Stanford University explored the safety and feasibility of administering young plasma to patients with mild to moderate Alzheimer's disease. Initial results indicated some improvement in functional ability, but the trial was small and lacked a control group, limiting the conclusiveness of the findings.
Antidotially one individual had a dramatica recovery of long term memory.
Results: Young plasma treatment improved short-term memory in the novel object recognition test and enhanced the spatial learning and memory in Morris water maze test and reversal Morris water maze test. Biochemical studies revealed that young plasma treatment reduced both tau and Aβ pathologies, as well as neuroinflammation in the mouse brain. However, we did not detect any significant changes in levels of synaptic proteins or the dentate gyrus neurogenesis in the mouse brain after the treatment with young plasma. Conclusions: These data indicate that young blood plasma not only ameliorates tau and Aβ pathologies but also enhances the cognitive function in 3×Tg-AD mice. These findings suggest that transfusion with young blood plasma could be a potentially effective treatment for AD.
[2016] Preclinical assessment of young blood plasma for Alzheimer disease
Chronic Kidney Disease (CKD)
Diabetes (Blood glucose levels) - meds eliminated or cut in half
Eczema
Energy Levels
Erectile Dysfunction
Graves' (Autoimmune ) - ophthalmic disease and -
Multiple Sclerosis
[51] Young Blood Plasma Multiple Sclerosis Study One-Month Results Show Dramatic Improvements in Critical…
Ocular (Eyesight improvement documented from 20/40 to 20/20)
Ostioperosis
[2023] Aging and age-related diseases with a focus on therapeutic potentials of young blood/plasma
[2015] Exposure to a Youthful Circulation Rejuvenates Bone Repair through Modulation of β-Catenin. Nat Commun 6:1–10
Parkinson’s Disease
[2020] Safety of Plasma Infusions in Parkinson’s Disease
Young fresh frozen plasma was safe, fea- sible, and well tolerated in people with PD, without seri- ous adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson’s Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended.
Parker JE, Martinez A, Deutsch GK, Prabhakar V, Lising M, Kapphahn KI, Anidi CM, Neuville R, Coburn M, Shah N and Bronte-Stewart HM. Safety of Plasma Infusions in Parkinson's Disease. Movement disorders: official journal of the Movement Disorder Society. 2020;35:1905-1913.
Pain
Lower spine/back pain
Peripheral Neuropathy
Torn rotator cuff Pain,
Sleep
Scaropienia (muscle pathology)
Truma (Recovery from Tramatic Injuries, Surgery or Illness)
Some studies have explored the use of young plasma for recovery enhancement post-surgery or in critical illness contexts. However, these studies often lacked robust design and did not conclusively establish efficacy.
Summary of Anecdotal Reports and Early-Stage Human Studies:
1. Alkahest Clinical Trials:
- Context: Alkahest, a biotech company co-founded by Tony Wyss-Coray, a pioneer in young blood research, has conducted several clinical trials exploring the effects of young plasma on various conditions, including Alzheimer’s disease.
- Report: In early clinical trials, there were anecdotal reports of mild cognitive improvements in elderly participants with Alzheimer's disease after receiving young plasma infusions.
- Reference: Wyss-Coray and colleagues published initial findings suggesting that plasma-derived proteins from young individuals could have therapeutic effects in Alzheimer's patients.
- Source: Montagne et al. (2020). "The spectrum of systemic factors that can reverse cognitive decline in aging." Nature Neuroscience, 23, 1093-1100. [Nature Neuroscience](https://www.nature.com/articles/s41593-020-0635-4)
2. Ambrosia’s Plasma Transfusion Study:
- Context: Ambrosia, a controversial company led by Jesse Karmazin, conducted a study offering young plasma transfusions to older adults for a fee, aimed at rejuvenation and improving health.
- Report: Participants reported subjective improvements in physical and cognitive functions. However, these reports are anecdotal and have not been backed by robust scientific data.
- Outcome: The study was criticized for lacking rigorous scientific controls and is not widely accepted in the medical community.
- Source: "First results from Ambrosia, the controversial young blood transfusion trial," MIT Technology Review. [MIT Technology Review](https://www.technologyreview.com/2017/01/10/154210/first-results-from-ambrosia-the-controversial-young-blood-transfusion-trial/)
3. Stanford University Study:
- Context: A small-scale study by Stanford University investigated the effects of young plasma on mild to moderate Alzheimer's patients.
- Report: There were anecdotal reports of slight improvements in cognitive abilities and daily living activities in some participants, but these were preliminary findings.
- Reference: The study was a precursor to more controlled trials and highlighted the potential for young plasma but also the need for further research.
- Source: "Plasma from young people shows rejuvenating effects on the brains of elderly Alzheimer’s patients," New Scientist. [New Scientist](https://www.newscientist.com/article/2152625-young-blood-infusion-gives-alzheimers-patients-a-reboot/)
4. Kip McGrath’s Personal Experience:
- Context: Kip McGrath, an Australian entrepreneur, has reported personal benefits from receiving young plasma transfusions.
- Report: McGrath described feeling more energetic and experiencing improved cognitive function after the treatments.
- Source: "Kip McGrath and his controversial young blood therapy," The Sydney Morning Herald. [Sydney Morning Herald](https://www.smh.com.au/national/kip-mcgrath-and-his-controversial-young-blood-therapy-20190301-p511jc.html)
5. Age-Related Muscle Weakness and Fatigue:
- Context: Some older individuals who have received young plasma infusions report feeling more vital and experiencing less muscle weakness and fatigue.
- Report: These anecdotal reports suggest potential benefits in overall energy levels and physical capabilities, though these claims are often subjective.
- Source: The reports are mostly gathered from testimonials and personal accounts rather than structured scientific studies.
- Reference: Some information can be found in lifestyle and health blogs discussing the personal experiences of individuals undergoing young plasma treatments.
Summary of Anecdotal Reports:
While these reports suggest potential benefits, they are anecdotal and lack the rigorous validation required to be considered scientifically credible. The placebo effect and subjective improvements cannot be ruled out. Further clinical trials with stringent controls and larger sample sizes are necessary to substantiate these claims and determine the efficacy and safety of young plasma treatments.
• Considerations for Credibility:
1. Placebo Effect: Many anecdotal reports might be influenced by the placebo effect, where participants believe they are experiencing benefits due to the treatment.
2. Lack of Controls: Many of these reports lack the controls and scientific rigor needed to draw definitive conclusions.
3. Regulatory and Ethical Concerns: The use of young plasma for anti-aging purposes raises ethical and regulatory questions, especially concerning the source and safety of the plasma.
• Conclusion:
Anecdotal evidence provides a preliminary glimpse into the potential benefits of young plasma, but it is crucial to approach these reports with caution. More robust and controlled studies are needed to verify the efficacy and safety of young plasma infusions for various age-related conditions.
For reliable and up-to-date information, monitoring ongoing clinical trials and peer-reviewed studies is essential. This approach ensures that any conclusions drawn are based on sound scientific evidence.
• References:
1. Montagne, A., et al. (2020). "The spectrum of systemic factors that can reverse cognitive decline in aging." Nature Neuroscience, 23, 1093-1100. [Nature Neuroscience](https://www.nature.com/articles/s41593-020-0635-4)
2. "First results from Ambrosia, the controversial young blood transfusion trial," MIT Technology Review. [MIT Technology Review](https://www.technologyreview.com/2017/01/10/154210/first-results-from-ambrosia-the-controversial-young-blood-transfusion-trial/)
3. "Plasma from young people shows rejuvenating effects on the brains of elderly Alzheimer’s patients," New Scientist. [New Scientist](https://www.newscientist.com/article/2152625-young-blood-infusion-gives-alzheimers-patients-a-reboot/)
4. "Kip McGrath and his controversial young blood therapy," The Sydney Morning Herald. [Sydney Morning Herald](https://www.smh.com.au/national/kip-mcgrath-and-his-controversial-young-blood-therapy-20190301-p511jc.html)
◉ First person experiences with Young Plasma
"I've long suspected that I had received young fresh frozen plasma in my infusions, as the difference was noticeable. Thanks again for including me in your study—I haven't felt that good in many years. I appreciate it and will follow your progress!" 2019
◉ Physicians Incorporating Young Plasma in their Practices:
◉ Plasma source and practitioners using yFFP in their practices.
Young plasma is available through providers that obtain plasma from Spectrum Plasma, a Texas based blood bank that has developed a state of the art blood banking facility. This plasma is sourced from young individuals between the ages of 18 and 24. The plasma sourced from Specturm has undergone the most rigerious testing of any plasma derived from any blood bank in the world.
❖ Bellaire suburb of Houston
• Dian Ginsberg MD FACOG ABAARM / The Ginstitute of Functional Medicine
Fellowship Metabolic Medical Institute/A4M
Advisor Functional Medicine University
Website: https://www.dianginsbergmd.com/
Email: dianginsberg.md@gmail.com
Dr Ginsberg is currentely in Fourth Place on the Rejuvenation Olympics leader board. Click their logo on the right for more information and complete listings.
Dr. Ginsberg’s most recent interview with the Podcaster Nopara73
❖ Arlington suburb of Dallas
• Jeffrey Gladden, MD, FACC / Gladden Longevity
Website: https://www.gladdenlongevity.com
Email: gladdenj@gladdenlongevity.com
• Physician Not Identified on site / Resurgence Wellness
Website: https://resurgencewellness.com
Email: chrischappell@resurgencewellness.com
❖ Austin
• Ddaniel Stickler MD / Apeiron Zoh
Website: https://apeironzoh.com
Email: drstickler@apeironcenter.com
• Khanh Nguyen, M.D. / Anti-Aging & Regenerative Medicine
Website: https://austinregen.com
Email: austinregen67@gmail.com
• No Primary Care Practitioner Identified / Everspan
Website: https://everspanlife.com
Email: drjulie@everspanlife.com
❖ San Antonio
• Dr. Derek Guillory / Root Causes
Website: https://rootcauses.com
Email: dg@rootcauses.com
Website: http://www.littlealsace.com/?page_id=10
Email: laucc.neel@gmail.com
❖ Houston
• Stanley C. Jones M.D. / Regenerative Health & Wellness
Website: https://stanleycjonesmd.com
Email: stanley.jones@yahoo.com
• Dr. Langley and Dr. Gallegosa / Thrive Medical Clinic
Thomas Casey founder of Specturm Plasma and Dr. Phillip Gallegos, founder of Thrive Medicine, Houston Texas
◉ Young Plasma Videos
◉ References
Literature Excerpts (Indented Text) Demonstrating the
Therapeutic and Age Regressive Potential of Young Plasma
[1][1864] [Bert P. De la greffe animale
[2][1957] Parabiosis Between Old and Young Rats
[3][1972] Mortality in Syngeneic Rat Parabionts of Different Chronological Age
[4][2005] Rejuvenation of aged progenitor cells by exposure to a young systemic environment
[5][2010] Platelets Contribute to Allograft Rejection Through Glutamate Receptor Signaling
[6][2014] Aged Mice Repeatedly Injected with Plasma from Young Mice: A Survival Study
[8][2015] Can we reverse the ageing process by putting young blood into older people?
{An excellent article detailing the early researchers that were instrumental is exposing the potential of young plasma.}
[9][2017] The Fountain of Youth: A tale of parabiosis, stem cells, and rejuvenation
[12][2019] Exosomes: biogenesis, biologic function and clinical potential
[13][2019] Undulating changes in human plasma proteome profiles across the lifespan
[14][2019] On the length, weight and GC content of the human genome
[15][2019] Looking to Young Blood to Treat the Diseases of Aging
[16][2019] Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage
[17] [2019] Undulating Changes in Human Plasma Proteome Profiles Across the Llifespan
[18][2020] Plasma dilution improves cognition and attenuates neuroinflammation in old mice
[19][2020] Reversing age- dual species measurement of epigenetic age with a single clock
[20][2020] Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin
[22][2020] Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?
[24][2021] Prospects for assessing the biological and immunological age of a person by blood factors
[25][2021] Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects
[26][2021] Diverse plasma membrane protrusions act as platforms for extracellular vesicle shedding
[27][2021] Friends and foes: Extracellular vesicles in aging and rejuvenation (Introduction)
[28][2021] The aging systemic milieu negatively regulates neurogenesis and cognitive function
[29][2022] Old plasma dilution reduces human biological age - a clinical study
[30] [2022] Circulating plasma factors involved in rejuvenation
[31][2022] Anti-Aging Composition Use Thereof US 2022/0233587 A1
[33][2023] Finding a fountain of youth in the blood
[34][2023] Multi-omic rejuvenation and lifespan extension on exposure to youthful circulation
[35][2023] Mechanism of mesenchymal stem cells and exosomes in the treatment of age-related diseases
[36][2023] Reversal of biological age in multiple rat organs by young porcine plasma fraction
[38][2023] Endothelial cells release microvesicles that harbor multivesicular bodies
[39][2023] Young plasma transfer recovers decreased sperm counts and restores epigenetics in aged testis
This article contains an excellent overview of the benefits seen in animal models thus far.
Early studies investigating the effect of systemic factors in blood plasma on aging and lifespan showed positive effects of young plasma on quality of life in aged animals (Kennedy et al., 2014). For instance, in an injury model, it has been stated that there are significant differences between the regeneration levels of skeletal muscle in an elderly indi- vidual receiving young blood plasma compared to an elderly individual not receiving plasma (Conboy et al., 2005). In another study, it was reported that age-related reductions in pancreatic beta cell proliferation returned to youthful levels only 2–3 weeks after sharing young plasma, and improvements in renal aging parameters were observed in elderly individuals whose young plasma was shared (Huang et al., 2018). In a study conducted to improve the age-related brain dysfunction, it has been observed that young blood plasma affected the increasing adult neurogenesis and enhanced hippocampal synaptic plasticity in cogni- tional levels and also has curative effect (Villeda et al., 2014). In liver damage due to age-related impaired autophagy, it has been suggested that application of young plasma moderately reduces liver damage by restoring the dysfunctional autophagy process in aged rats; therefore, young plasma has a beneficial property in ameliorating aging-related organ damage (Liu et al., 2018). Many studies similar to the above have shown the healing properties of youth plasma in different tissues/ organs by certain cellular processes/paths in favour of healthy aging but it is not known how the epigenetic mechanisms are affected by these transfers. It is very important point because aging causes abnormality in epigenetic mechanisms which end up with epigenetic disorders.
Research shows that young blood can rejuvenate old individuals by transferring cells, vesicles, and molecules that restore function and organ integrity. A study involving old female rats compared those receiving young rat plasma injections (Group T) with untreated controls (Group C). The treated group showed no deaths between ages 26 and 30 months, whereas control group mortality began at 26 months. Blood DNA methylation (DNAm) analyses indicated that DNAm age increased rapidly in youth, stabilized after 27 months, and remained consistently lower in treated rats than in controls until their natural death. Treated and control groups exhibited distinct DNA methylation profiles. Promoter methylation analysis revealed enrichment in gene ontology terms associated with insulin-like factors and immune-related cytokines and chemokines. The findings suggest that young plasma therapy is a promising noninvasive strategy for epigenetic rejuvenation and health enhancement in the elderly.
[41][2024] Clinical applications of stem cell-derived exosomes
Recent research into heterochronic parabiosis has shown significant rejuvenating effects of young blood on old tissues, but the precise mechanisms are not fully understood. This study illustrates that small extracellular vesicles (sEVs) from young mice plasma can reverse aging effects at molecular, mitochondrial, cellular, and physiological levels. Intravenous injections of these sEVs into aged mice extended their lifespan, reduced signs of aging, and improved function in various tissues. Proteomic analysis of treated tissues revealed major alterations in protein expressions linked to metabolic processes. Mechanistically, young sEVs were found to enhance PGC-1α expression, both in vitro and in vivo, via their microRNA content. This upregulation of PGC-1α improved mitochondrial functions and addressed mitochondrial deficits, thus countering age-related degeneration and dysfunction in aged tissues. The study underscores the potential of young sEVs to rejuvenate aged cells by enhancing mitochondrial energy metabolism.
There is increasing evidence that young plasma can have restorative effects in aging, especially noted in the brains of old rats and in age-related diseases. Studies have shown that human cord plasma can enhance synaptic plasticity and cognition in aged mice, potentially through a factor called tissue inhibitor of metalloproteinases 2. Furthermore, administration of plasma proteins in old rats has been linked to a significant reversal of epigenetic age. In a recent study, it was demonstrated for the first time that continuous treatment of old rats with young rat plasma not only moderately rejuvenates them epigenetically but also extends their lifespan and improves their physical appearance, such as smoother fur. This effect is possibly mediated by the IGF-1/IIS system and cytokine and chemokine networks. This suggests that young plasma therapy might be a natural and minimally invasive way to promote epigenetic rejuvenation and overall health improvement. Summary by ChatGPT.
[44][2024] Aging and age-related diseases with a focus on therapeutic potentials of young blood/plasma
[45] https://www.age-regression.com/rir
[46] Personal Communications
Definitions of Terms Utilized on this Page
Age gap
The difference between a biological age measurement and the expectation of that measurement for a given chronological age.
Heterochronic parabiosis
An experimental paradigm where the circulatory systems of a young and old animal are surgically joined together.
Biological age
The level of biological functioning of an organism, organ or cell as assessed in comparison to an expected level of function for a given chronological age.
CERS
The Chrono-Epigenetic Regulation System (CERS) Interface between environmental, biological and psychological control system of development, immunity and aging. The three layers involved are Chronokines, epigenetic and genetic layers. Combine they form a complex and dynamic regulatory processes governing human physiological and aging control.
Chronological age
The amount of time an organism has been alive for, typically measured in years for humans and tracked by birthdays.
Partial epigenetic reprogramming
Delivery of factors that can de-differentiate cells into induced pluripotent stem cells, typically short term, to de-age the epigenetic state of cells.
Proteomics
Proteomics, the large-scale study of the proteins, focuses on the systematic identification, quantification, and analysis of all proteins in a biological sample. It aims to understand the structure, function, and interactions of the entire protein complement of a cell line, tissue, or organism under specific conditions. Employing technologies like mass spectrometry, protein microarrays, and bioinformatics, proteomics analyzes protein expression, structure, post-translational modifications, and interactions. This field is crucial for understanding biological processes, diseases, and in the development of new therapies and diagnostics.
In human plasma, there are approximately 10,000 to 15,000 proteins and small molecules that can be detected with current technologies. This diverse range includes proteins, peptides, lipids, metabolites, and other biologically active compounds. The dynamic range of these protein concentrations is vast, making it a challenge to detect and quantify especially those present at low levels.
• Companies Developing Plasma or Plasma Derived Therapies
Alkahest: This company, now a subsidiary of Grifols, focuses on developing plasma formulations by pooling blood from young donors and selectively removing unwanted immune molecules. Alkahest’s research has primarily targeted neurological conditions like Alzheimer's and Parkinson's disease, exploring the cognitive benefits of plasma-derived productsThe company was co-founded in 2014 by Tony Wyss-Coray, a neurologist at Stanford University, after he published papers showing that the rejuvenating effect of parabiosis extended to the mouse brain. (Smithsonian Magazine).
[2020] Safety and tolerability of GRF6019 in mild‐to‐moderate Alzheimer's disease dementia
GRF6019 is a highly specialized plasma fraction developed by Alkahest in partnership with Grifols, designed for the treatment of neurodegenerative diseases like Alzheimer's. This therapy emerges from research indicating that certain components of plasma could potentially reverse aspects of aging in the brain due to their regenerative and anti-inflammatory properties.
The preparation of GRF6019 involves selecting approximately 400 proteins from plasma, with a focus on removing clotting factors and immunoglobulins to enhance safety and tolerability. This process ensures that the treatment does not require matching donor and recipient blood types, simplifying its administration. GRF6019 targets the enhancement of cognition, reduction of inflammation, and restoration of neurogenesis.
Clinical trials of GRF6019 have shown promising results in terms of safety and efficacy. It has completed Phase 2 trials for mild to moderate Alzheimer’s disease, with studies indicating that it was well-tolerated and participants showed stable or negligible decline in cognitive and functional measures over six months. The treatment is also being evaluated in patients with severe Alzheimer's, focusing on its safety, tolerability, and potential effects on patients' mental states and daily activities (AlzForum) (Alkahest) (Alzheimer's News Today).
For more detailed information, you can refer to Alkahest's updates on their clinical trials and therapeutic developments on their official website [Alkahest](https://www.alkahest.com/pipeline/akst-grf6019/).
Young blood cocktail stops Alzheimer's decline, early clinical trial reports
CSL Behring / CSL Plasma: This company is a major player in the global blood plasma products market, holding the largest market share in 2021. CSL Behring operates numerous plasma collection centers worldwide and focuses on innovative biotherapeutic products【7†source
Elevian: Elevian is developing treatments based on a specific blood-borne protein, GDF11, which has shown promise in preclinical studies to restore youthful characteristics in various tissues. The company is preparing to test its lab-grown version of GDF11 in human trials, aiming to treat age-related diseases like stroke【8†source】It was co-founded in 2018 by Amy Wagers, who was on the Stanford parabiosis revival team and is now a professor of stem-cell and regenerative biology at Harvard University.
Grifols: Based in Spain, Grifols is significant in the bioscience sector, providing plasma-based protein therapies. The company runs numerous plasma collection centers and focuses on expanding its plasma collection capacity through facility expansions and acquisitions (BCC Research Blog).
Takeda: Another leading company, Takeda specializes in plasma-derived therapies, particularly for rare diseases, operating over 200 plasma collection centers globally (BCC Research Blog).
Spectrum Plasma: is a company that focuses on plasma collection and emphasizes contributing positively to the community by producing health-improving products. They adopt a fresh approach to how individuals can donate plasma and whole blood, providing immediate rewards to donors in the form of Tango gift cards. Their operations are based in multiple locations across the United States including California, Texas, and Nevada (Spectrum Plasma) (Corporation Wiki).
• BLOGS:
Longevity on Reddit
(search for “Young Plasma”)
https://www.reddit.com/r/longevity/
Aging Matters; Aging Matters: Out With the Old Blood
Molecules in the Blood that Signal Self-Destruction
How Young Blood Differs from Old
• NOTES / FUTURE RESEARCH
[2022] Molecular hallmarks of heterochronic parabiosis at single-cell resolution
[2020] Circulating plasma factors involved in rejuvenation
[2018] Plasma proteomic signature of age in healthy humans
[2021] Proteomics and Epidemiological Models of Human Aging
[2021] Proteomics in aging research- A roadmap to clinical, translational research
◉ The Next Page in the Young Plasma Series:
An article outlining the potential benefits of young plasma on the wellbing of those those donating as well as recieving young plasma, and on the healcare infastructure of the US and the World.
Click on the title below to go to Tom Casey’s insightful article: