Therapeutic plasma exchange with intravenous immunoglobulin (TPE-IVIG)

infusion · 2024–present

category:infusion

delivery:Therapeutic plasma exchange is a standard apheresis procedure performed in a clinical setting: the patient's blood is processed through an apheresis machine that separates plasma from cellular components; plasma is removed and discarded; the cellular components are returned to the patient along with replacement fluid (typically albumin in saline). The Circulate protocol described in the *Aging Cell* trial added intravenous immunoglobulin (IVIG) at the end of the TPE session in the relevant arm. The trial used biweekly sessions in two arms (TPE alone, TPE+IVIG), monthly sessions in a third arm (TPE alone), and saline-only sham in the placebo arm, for six sessions total over approximately three months. Each session takes several hours and is performed in a clinical apheresis setting by trained personnel.

price tier:top_only

era:2024–present

current status:current

regulatory:off_label

SHORT PITCH (AS SOLD)

Therapeutic plasma exchange combined with intravenous immunoglobulin, marketed as reducing biological age by 2.6 years on average as measured by a panel of 35 epigenetic clocks.

THE ACTUAL EVIDENCE

One single-blind randomized placebo-controlled trial, N=42, published in *Aging Cell* (May 2025), with a disclosed conflict of interest (the investigators are members of the commercializing company Circulate, Inc.; the paper states it received no specific funding): biweekly TPE+IVIG showed a 2.61-year average reduction in biological age across the 35-clock panel (FDR=6.22e-05); monthly TPE alone showed 1.32 years (FDR=2.42e-02); placebo showed age acceleration. The primary outcome is a surrogate endpoint (epigenetic age) not validated as a causal mediator of mortality at the individual level. No hard-endpoint (mortality, disease incidence, functional capacity) data. Two adverse events required discontinuation across all treatment arms; the procedure was generally well-tolerated in the trial population. Independent replication by groups unaffiliated with the sponsor has not been published.

PRACTITIONERS

Buck Institute for Research on Aging / Circulate Health

INGREDIENTS

CASES

tpe-ivig-2024-present

CLAIMS

Biweekly therapeutic plasma exchange combined with intravenous immunoglobulin produces an average 2.61-year reduction in biological age as measured across a panel of 35 epigenetic clocks in a healthy adult population over 50. unreplicated
The TPE-IVIG protocol reverses biological aging in healthy adult recipients, producing measurable rejuvenation across multiple molecular domains including immune (-9.7 years), inflammatory (-7.1 years), and other Systems Age clocks. unreplicated
Monthly therapeutic plasma exchange without IVIG produces an average 1.32-year reduction in biological age across a panel of 35 epigenetic clocks and extends healthspan in healthy adult recipients over 50. unreplicated

SOURCES

NOTES

Therapeutic plasma exchange with intravenous immunoglobulin (TPE-IVIG) is a private clinical service offered by Circulate Health on the basis of the May 2025 Aging Cell trial conducted at the Buck Institute. The intervention is the latest installment in the lineage of biological-substance-transfer rejuvenation that runs from Brown-Séquard (1889) through Voronoff (1920) to Niehans (1931). The trial methodology is substantially more rigorous than the historical precedents (randomized, placebo-controlled, single-blind, with multi-omics outcome measurement) but inherits the same structural conditions: a disclosed conflict of interest in which the investigators are members of the commercializing company, surrogate-endpoint primary outcomes, small sample, short follow-up, and absence of independent replication. The protocol is currently being marketed at the top of the elite longevity-medicine market.