Young Plasma Exchange (TPE)
Therapeutic plasma exchange using plasma from young healthy donors (ages 18-25) to rejuvenate biological markers and potentially reverse aspects of aging
Bottom Line
Young Plasma Exchange is one of the most cutting-edge longevity interventions available. The May 2025 Buck Institute clinical trial showed a 2.6-year reduction in biological age using multi-omic biomarkers, the first placebo-controlled human trial to demonstrate this effect.
Ben Greenfield calls it "probably the biggest game-changer I've ever experienced for feeling like I've wound back the clock to eighteen years old." However, it's expensive, only available at specialized clinics (primarily in Texas), and long-term effects remain unknown.
Promising early science, dramatic anecdotal reports, but still experimental. For those with resources seeking cutting-edge longevity interventions, this is worth considering. For most people, stick with proven interventions first.
Science
Mechanisms:
- Dilution of pro-aging factors: Removes accumulated inflammatory proteins, damaged immunoglobulins, and pro-aging factors from circulation
- Introduction of young plasma factors: Young plasma contains growth factors, peptides, exosomes, and regenerative components
- Immune system reset: May help recalibrate immune function
- Epigenetic changes: Multi-omic analysis shows changes in epigenome, proteome, metabolome, and glycome
Key Research:
- Fuentealba et al. (2025) in Aging Cell: First randomized placebo-controlled trial
- 44 adults over 50 years old
- Bi-weekly TPE + IVIG: 2.61 year biological age reduction
- TPE alone: 1.32 year reduction
- Measured using 36 epigenetic clocks
- Improvements in balance and strength
- Safety profile: 0.42% mild allergic reaction rate (1 in 240 procedures)
What Was Measured:
- Epigenetic clocks (DNA methylation patterns)
- Proteome changes
- Metabolome shifts
- Glycome modifications
- Immune system markers
- Physical measures (balance, strength)
Earlier Animal Research:
- Parabiosis studies (connecting circulatory systems of young and old mice) showed rejuvenation effects
- Young blood factors improved cognitive function, muscle repair, and organ function in aged animals
Limitations:
- Small sample size (44 participants)
- Long-term effects unknown
- Optimal frequency and duration unclear
- Mechanism not fully understood
- May be dilution effect rather than young factors specifically
Supporting Studies
6 peer-reviewed studies
View all studies & compare research →Practical Protocol
Standard Protocol (Austin Regenerative Therapy):
Day 1:
- Remove ~1 liter of old plasma
- Replace with IV vitamins and saline
Day 2:
- Remove second liter of plasma
- Infuse 2 liters of Young Fresh Frozen Plasma (yFFP)
- Plasma from healthy donors aged 18-25
Buck Institute Trial Protocol:
- Bi-weekly TPE with or without IVIG
- Or monthly TPE
- Duration: Several months
Procedure Details:
- Takes several hours per session
- IV access required
- Performed at specialized clinics
- Requires medical supervision
Optional Add-Ons (at some clinics):
- IVIG (intravenous immunoglobulin) - enhanced results in trial
- Targeted joint injections with young plasma
- Stem cell combinations
- Exosome infusions
Post-Procedure:
- Most resume normal activity same day
- Some report immediate energy boost
- Monitor for allergic reactions
- Follow-up testing at 3-6 months recommended
Risks & Side Effects
Known Risks:
- Allergic reactions: 0.42% rate (mild, in Buck trial)
- Infection risk: Standard IV procedure risks
- Transfusion reactions: Possible with any blood product
- Citrate toxicity: Can occur during plasmapheresis
- Hypotension: Temporary blood pressure drop possible
Potential Concerns:
- Unknown long-term effects: Procedure too new
- Immune system impact: Unclear long-term immune effects
- Disease transmission: Extremely low risk with screened donors
- Regulatory status: Not FDA-approved for anti-aging
Contraindications:
- Active infections
- Bleeding disorders
- Severe cardiovascular disease
- Allergy to blood products
- Pregnancy
- Immunocompromised states (relative)
Legal Status:
- Available in Texas and some other states
- Regulatory landscape varies
- Not covered by insurance for longevity purposes
Risk Level: Moderate (experimental procedure, limited long-term data)
Who It's For
Ideal Candidates:
- Those with significant resources for cutting-edge longevity
- People who have optimized foundational interventions first
- Individuals over 50 seeking biological age reversal
- Those comfortable with experimental procedures
- People who can travel to specialized clinics
May Benefit:
- Those with accelerated biological aging
- Individuals with high inflammatory markers
- People seeking performance/recovery enhancement
- Longevity-focused biohackers
Should Skip:
- Those seeking proven, affordable interventions
- People who haven't optimized basics (sleep, exercise, nutrition)
- Anyone with contraindications listed above
- Those uncomfortable with experimental procedures
- People who can't afford the cost
Prerequisites:
Should have already optimized: sleep, exercise, nutrition, stress management, and basic supplements before considering advanced interventions like this.
How to Track Results
What to Measure:
Before/After Testing:
- Biological age testing (epigenetic clocks)
- TruDiagnostic
- Elysium Index
- GrimAge, PhenoAge clocks
- Comprehensive blood panel
- Inflammatory markers (CRP, IL-6)
- Metabolic markers
Subjective Measures:
- Energy levels
- Cognitive clarity
- Skin appearance
- Recovery from exercise
- Sleep quality
Physical Measures:
- Grip strength
- Balance tests
- Body composition
Timeline:
- Immediate: Some report same-day energy boost
- 1-4 weeks: Subjective improvements
- 3-6 months: Biological age testing recommended
Signs It's Working:
- Improved energy and vitality
- Better cognitive function
- Enhanced recovery
- Reduced biological age on testing
- Improved inflammatory markers
Top Products
Clinics Offering Young Plasma Exchange:
Austin Regenerative Therapy (Texas) - Ben Greenfield's choice - Young Plasma™ protocol - austinregen.com
Circulate Health
- FDA-cleared TPE system
- Connected to Buck Institute research
- Available at 20+ functional health clinics
NextHealth
- Multiple locations
- Various regenerative protocols
Testing:
- TruDiagnostic - Epigenetic age testing
- Elysium Health Index - Biological age
Note: Always verify clinic credentials and doctor qualifications. This is a medical procedure requiring proper oversight.
Cost Breakdown
Estimated Costs:
| Treatment | Approximate Cost |
|---|---|
| Single TPE session | $3,000-5,000 |
| Full protocol (2-day) | $10,000-15,000 |
| With add-ons (stem cells, etc.) | $15,000-25,000+ |
| Repeat treatments | Additional cost each time |
Additional Costs:
- Travel to Texas/specialized clinic
- Pre/post testing ($500-2,000)
- Accommodation during treatment
- Follow-up visits
Insurance:
- Not covered for longevity/anti-aging
- May be covered for specific medical conditions (rare)
Cost-Per-Benefit:
Very high cost. Consider only after optimizing free/low-cost interventions (sleep, exercise, nutrition, cold exposure, sauna, etc.).
Podcasts
#036 Judith Campisi, Ph.D. on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging
Dr. Judith Campisi discusses cellular senescence, its role in aging, and potential therapeutic...
The Surprising Science Of Injecting Young Blood, Salmon Sperm & Stem Cells Into Your Face (And Other Places) With Dr. Khanh Nguyen
Ben Greenfield visits Dr. Khanh Nguyen at Austin Regenerative Therapy for three days of advanced...
What it takes to be “Young Forever!” | Mark Hyman : 1385
Mark Hyman joins The Human Upgrade to discuss what it takes to be “young forever!” | mark hyman...
TPE... The Future of Longevity | EP 137
Dr. John Leakey and Dr. Payman Danielpour discuss therapeutic plasma exchange (TPE) as a...
Discussed in Podcasts
25 curated moments from top health podcasts. Click any timestamp to play.
Bryan Johnson's shift from young blood to plasma exchange
Dr. Norman Swan explains how saline controls produced the same rejuvenation as young blood, revealing that TPE works by diluting toxic senescent cell substances rather than adding youthful factors. Johnson moved from his son's plasma to total plasma exchange.
"when they gave, well, it's not so much a placebo, a control substance, which was saline, still an infusion, you got the same effect. And it turns out what's going on here is probably a dilution of the toxic substances from senescent cells."
Homeostasis fights back against longevity interventions
Dr. Swan warns that the body's homeostatic mechanisms may oppose chronic high-dose interventions, potentially negating initial benefits as the body pushes back to maintain its equilibrium.
"if you take these supplements, it's likely that what happens is that the body reacts to them. So if you take rapomycin and you shift that TOR pathway, the body recognizes that as abnormal and opposes it and pushes back."
Critical take on n-of-1 biohacking experiments
Dr. Swan provides a measured scientific critique of Bryan Johnson's approach, noting that doing dozens of interventions simultaneously without controls makes it impossible to identify what actually works.
"He's not doing it in any kind of scientific way, really."
Therapeutic plasma exchange showed clear benefits in 500 Alzheimer's patients
Dr. Wyss-Coray describes a study where therapeutic plasma exchange — removing old plasma and replacing it with albumin containing other factors — showed clear significant benefits in 500 patients with Alzheimer's disease. Companies now offer this treatment commercially.
"where they first removed their plasma, this is called therapeutic plasma exchange. And then infused them back with a major blood component, this albumane, which also contains other factors. And they saw clear significant benefits. And this was in 500 patients."
Multiple pro-youthful proteins identified — GDF11, clusterin, and IGF1 in young blood
The lab has identified several specific proteins in young blood that drive rejuvenation, including GDF11, IGF1, and clusterin (also called apolipoprotein J). Recombinant synthetic clusterin injected into mice mimicked some of the rejuvenating effects of young blood, suggesting future targeted therapies.
"GDF11 is one of them that has been described"
TPE explained as an oil change for the body
The hosts explain that TPE filters the liquid component of blood (plasma), removing senescent cells, inflammatory cytokines, and toxic protein complexes that accumulate with age.
"filtering or in a very simple way to give you an oil change okay filtering the liquid component of your blood which is called plasma which really holds a lot of the senescent cells or the dying cells or the inflammatory cells in the body that cause disease"
Cumulative toxin clearance across multiple TPE sessions
The doctors outline how repeated TPE sessions progressively clear more toxins, from 75% after the first round to 98-99% after four rounds spaced three to four months apart.
"The idea is the first time you undergo TPE, it will clear about 75% of all those toxins and things that we talked about. The second round would get you up to 85% of the toxins. The third round would get you to 95% of the toxins, and then the fourth would give you closer to 98, 99%."
TPE for Alzheimer's, long COVID, and autoimmune conditions
The hosts discuss emerging research showing TPE can reduce or eliminate long COVID symptoms by clearing immune complexes stuck in plasma, alongside its established use for autoimmune disorders.
"there are a few scientific articles that say by doing therapeutic plasma exchange, that the symptoms of long COVID either go away or decrease significantly. Now, it's just common sense, right? We're taking all of these immune complexes that are stuck in your body,"
Biohackers endorsing TPE as superior to supplements
The doctors note that prominent biohackers like Dave Asprey consider TPE the best longevity intervention, superior to taking hundreds of supplements, because results are visually verifiable through cloudy versus clear plasma.
"they all believe in TPE to another level. They've all done it. They say this is probably the best way to do it without having to take 500 different pills and supplements and all this other stuff. This works because you actually see it with your own eyes."
Young Plasma Exchange Discussion
I think the other question though is, you know, cells also build up kind of these aggregates and other, you know, nasty kind of by-projects and accumulate what happens to them.
"People are doing this in the early 20th century. Basically, you can take two mice and connect their circulatory systems."
ASFA evidence categories for apheresis treatment
Dr. Miller explains the four-tier ASFA evidence classification system for apheresis, from Category 1 (mainstay treatment) to Category 4 (contraindicated), providing a framework for understanding which conditions have the strongest evidence.
"category one means that apheresis is the mainstay of treatment. It is really the only treatment. It's the best treatment for the disease. Category two means that it's used in conjunction with something else like medication. And it's definitely a part of the treatment plan."
AMBAR trial results for Alzheimer's disease
Dr. Miller describes the landmark AMBAR trial results showing 70% of moderate Alzheimer's patients halted disease progression with TPE, compared to near-universal decline in the placebo group, with many treated patients actually improving.
"About 70% of the treated patients didn't show any decline at all."
Who to Follow
Researchers:
- Eric Verdin, MD - CEO of Buck Institute, Circulate Health co-founder
- David Furman, PhD - Buck Institute researcher, multi-omics expert
Practitioners:
- Ben Greenfield - Prominent advocate, personal experience
- Darshan Shah, MD - NextHealth founder
Clinics:
- Austin Regenerative Therapy (Dr. Khanh Nguyen)
- Circulate Health network
Synergies & Conflicts
Pairs Well With:
- Sauna - Heat shock proteins, detox
- Cold exposure - Hormesis
- Time-restricted eating - Autophagy
- Stem cell therapies (often combined at clinics)
- NAD+ IV infusions
Optimize First:
Before considering TPE, ensure these are optimized: - Sleep quality - Exercise routine (Zone 2 + strength) - Nutrition - Stress management - Basic supplements (D, omega-3, etc.)
Post-Treatment Support:
- Anti-inflammatory diet
- Adequate protein for recovery
- Continued exercise
- Sleep optimization
Testing Stack:
- Biological age test before/after
- Comprehensive blood panel
- Inflammatory markers
What People Say
Ben Greenfield's Experience:
Ben Greenfield received young plasma exchange at Austin Regenerative Therapy and reported: - Immediate improvement in energy and vitality - Weight went from 185 to 202 lbs (muscle, no fat gain) - Dramatically improved skin appearance - "Biggest game-changer I've ever experienced" - Named it one of his Top 10 Biohacks of 2025
Clinical Trial Results:
Community Feedback:
Caveats: