Research has demonstrated that replacing aged plasma with albumin solution rejuvenates tissues, activates stem cells, and measurably reduces biological age — by up to 2.6 years in a randomized controlled trial.
The foundational insight came from parabiosis research — experiments in which the circulatory systems of old and young mice were surgically connected. Researchers at UC Berkeley found that old mice sharing blood with young mice showed reversal of age-related decline across multiple organ systems, including muscle, liver, brain, and bone.
But the young mice aged. This finding was critical: it demonstrated that aging is not simply the loss of youthful factors. It is driven by the accumulation of harmful factors in old blood.
In 2020, the same UC Berkeley team, led by Irina and Michael Conboy, demonstrated that simply diluting old blood plasma — replacing it with saline and albumin, with no young blood components whatsoever — produced the same rejuvenating effects in mice. Muscle repair improved, liver fibrosis decreased, neuroinflammation declined, and neurogenesis increased.
The implication was striking: aging may be driven not by what the body lacks, but by what it has accumulated. And therapeutic plasma exchange — a procedure that has been performed clinically for over 50 years — is precisely the intervention that removes these accumulated factors.
Working with Dr. Dobri Kiprov at Global Apheresis, the Berkeley researchers brought this insight to humans. In a clinical study published in GeroScience, Kim et al. showed that multiple rounds of therapeutic plasma exchange produced a global shift toward a younger systemic proteome. The study identified 10 novel protein biomarkers of biological age and demonstrated that TPE:
Kim D, Kiprov DD, Luellen C, et al. “Old plasma dilution reduces human biological age: a clinical study.” GeroScience. 2022;44(6):2701–2720.
In 2025, a randomized placebo-controlled trial published in Aging Cell provided the most rigorous evidence to date for TPE as a longevity intervention. The study, a collaboration between the Buck Institute for Research on Aging and Dr. Kiprov, used multi-omics analysis to measure the biological effects of plasma exchange across multiple molecular systems.
The trial enrolled 42 healthy adults over the age of 50, randomized to TPE regimens or placebo. Intensive regimens consisted of TPE with or without IVIG administered in three cycles — each cycle comprising two treatments in one week followed by a three-week break, totaling six procedures over approximately three months. A separate arm received monthly TPE for six months.
Intensive TPE with IVIG demonstrated up to 2.61 years of biological age reduction as measured across 35–36 validated epigenetic clocks.
Rejuvenation was observed across the epigenome, proteome, metabolome, glycome, and immune cell populations — a synchronized shift toward younger biological states.
TPE was safe and well-tolerated across all treatment arms, with only two adverse events requiring discontinuation in the entire trial.
This trial is significant because it measured biological age reduction using a comprehensive multi-omics approach — not a single biomarker, but coordinated changes across 35–36 epigenetic clocks, the proteome, metabolome, glycome, and immune cell composition. The consistency of rejuvenation across these independent biological systems strengthens the evidence that TPE produces genuine physiological change, not an artifact of any single measurement.
Fuentealba M, Kiprov D, Schneider K, et al. “Multi-omics analysis reveals biomarkers that contribute to biological age rejuvenation in response to single-blinded randomized placebo-controlled therapeutic plasma exchange.” Aging Cell. 2025;(8):e70103.
Senescent cells release the senescence-associated secretory phenotype (SASP) — inflammatory molecules that circulate in plasma and drive inflammation, tissue damage, and further senescence in neighboring cells. TPE physically removes these circulating SASP factors from the blood.
Chronic low-grade inflammation — sometimes called “inflammaging” — is driven by elevated IL-6, TNF-α, IL-1β, and other pro-inflammatory cytokines. TPE removes these mediators and replaces them with albumin, which itself has well-documented anti-inflammatory and antioxidant properties.
Aged plasma carries inhibitory signals that suppress tissue repair and regeneration. Removing these signals reawakens regenerative pathways. Kim et al. (2022) demonstrated that TPE restored pro-regenerative regulators to youthful levels.
Plasma contains thousands of regulatory proteins that coordinate cellular function throughout the body. With age, this proteome becomes progressively dysregulated. TPE resets the circulating proteome, producing what Kim et al. described as a global shift toward a younger systemic proteome.
Persistent organic pollutants, heavy metals, and endocrine-disrupting compounds accumulate in plasma over a lifetime and may contribute to oxidative stress and DNA damage. TPE physically removes these compounds. Fuentealba et al. (2025) documented coordinated molecular rejuvenation across multiple biological systems following plasma exchange.
Fuentealba et al. (2025) showed that TPE produces measurable epigenetic changes reflected across 35–36 biological age clocks — with intensive regimens demonstrating up to 2.61 years of biological age reduction as measured by validated epigenetic algorithms.
Proactive, health-conscious individuals who are already investing in their long-term health and want to address aging at the molecular level. There is no minimum age requirement, though published research has focused on adults over 50.
Longevity protocols are not one-size-fits-all. Our physicians design treatment plans based on your health profile, goals, and baseline biomarkers. Most patients begin with an initial intensive series followed by periodic maintenance — quarterly, bi-annually, or as determined by response. Flexible scheduling is available for patients traveling to our clinic.
Biological age and relevant biomarkers are tracked at baseline and over time, allowing our physicians to measure treatment response and adjust protocols accordingly. This is data-driven medicine, not guesswork.
TPE addresses the circulating environment — one component of a comprehensive longevity program. It works alongside exercise, nutrition, sleep optimization, and targeted supplementation. Our physicians can discuss how TPE integrates with your broader health strategy.
Schedule a free discovery call with our physicians to discuss your longevity goals and whether therapeutic plasma exchange is the right addition to your health strategy.
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