Parabiosis: Young Blood and Old Bodies

In 1864, French physiologist Paul Bert stitched two rats together.

Not metaphorically. He surgically joined them so they shared a circulatory system—blood flowing from one animal into the other and back. He called it parabiosis, from the Greek for "living beside."

Bert was interested in physiology, not aging. But his technique would eventually reveal something profound: old animals connected to young animals become younger. Their organs rejuvenate. Their brains function better. Their lifespan extends.

The obvious question: what's in young blood that old blood lacks? And can we bottle it?

The Heterochronic Experiments

The key experiments came in the 2000s, from labs at Stanford and Harvard.

Heterochronic parabiosis means joining animals of different ages—an old mouse to a young mouse. Their circulatory systems merge. Blood factors, hormones, cells, everything in the bloodstream gets shared.

What happens to the old mouse?

The results were startling: - Muscle regeneration improved - Liver function enhanced - Neurogenesis (birth of new neurons) increased in the hippocampus - Cognitive performance improved - Heart function got better - Bone healing accelerated

The old mouse didn't become young. But it became biologically younger on multiple measures. Tissues that had declined with age showed partial reversal.

What about the young mouse? This is the disturbing part. The young mouse showed the opposite effects. Exposure to old blood impaired regeneration, reduced neurogenesis, and accelerated some markers of aging.

Young blood helps old bodies. Old blood harms young bodies.

The Search for the Magic Factor

The obvious next step: figure out what's different between young and old blood, and give old animals the good stuff without needing to surgically attach them to teenagers.

This search has identified several candidates.

GDF11 (Growth Differentiation Factor 11): In 2014, Amy Wagers' lab at Harvard reported that GDF11 declined with age and that supplementing it could reverse cardiac hypertrophy in old mice. This made headlines. Subsequent studies have been more mixed—some labs couldn't replicate the findings, and there's debate about whether GDF11 actually declines with age or whether the original assays were confounded.

TIMP2 (Tissue Inhibitor of Metalloproteinases 2): Identified in 2017 by Tony Wyss-Coray's lab at Stanford, TIMP2 is enriched in human umbilical cord blood and can improve hippocampal function in old mice when administered alone.

Klotho: A protein that declines with age and, when supplemented, improves cognitive function in mice. It's being explored for neurological applications.

Oxytocin: The "bonding hormone" declines with age and may contribute to muscle regeneration deficits in old animals.

The picture that's emerging is complex. There isn't one magic factor. Young blood contains a cocktail of proteins, metabolites, and other molecules that together create a rejuvenating milieu. Old blood contains factors that actively promote aging.

Rejuvenation may require both adding the good and removing the bad.

Plasma Exchange

If the benefit comes from blood factors rather than cells, maybe you don't need young blood at all. Maybe you just need to dilute the old blood.

In 2020, Irina Conboy's lab at Berkeley tested this with neutral blood exchange—replacing half of an old mouse's plasma with saline plus albumin. No young factors added. Just dilution.

The results: Improved muscle regeneration, reduced liver adiposity, and enhanced hippocampal neurogenesis. Comparable to parabiosis.

This suggests that much of the benefit of young blood comes from removing old blood factors rather than adding young ones. The pro-aging signals in old plasma may be more important than the pro-youth signals in young plasma.

If true, this is good news therapeutically. Diluting plasma is much simpler than identifying and manufacturing youthful factors. Plasma exchange (plasmapheresis) is already an established medical procedure used for autoimmune diseases.

Clinical trials are exploring whether plasma exchange or plasma dilution can produce rejuvenating effects in humans. Early results are intriguing but preliminary.

The Ambrosia Debacle

Where there's scientific excitement, there's exploitation.

In 2017, a startup called Ambrosia began offering transfusions of young blood plasma to anyone willing to pay $8,000. The company framed it as a clinical trial, but critics noted it lacked a control group, proper endpoints, or any of the features of legitimate research.

Ambrosia's founder, Jesse Karmazin, cited the parabiosis research to justify the treatment. He claimed participants showed improvements in biomarkers. No peer-reviewed results were ever published.

In 2019, the FDA issued a statement warning consumers about young blood treatments, noting "there is no proven clinical benefit" and "significant risks." Ambrosia shut down.

This episode illustrates a recurring problem in longevity research: the gap between legitimate science and commercial hype is often exploited. Real researchers are studying blood factors carefully. Meanwhile, companies sell unproven treatments to wealthy people desperate to live longer.

The parabiosis research is real and interesting. The claim that you can buy young blood transfusions and become younger is not supported by evidence.

What We Actually Know

Let's be precise about the state of the science.

In mice: - Heterochronic parabiosis rejuvenates multiple organs in old animals - The effect appears to be mediated by circulating factors, not cells - Specific factors (GDF11, TIMP2, others) have been implicated but none fully accounts for the effect - Diluting old plasma without adding young factors produces similar benefits - The effects are real but partial—not a complete reversal of aging

In humans: - We don't know if parabiosis effects translate - Small trials of young plasma transfusion haven't shown clear benefits - Plasma exchange trials are underway - Commercial "young blood" offerings are not scientifically validated

The open questions: - What is the optimal cocktail of factors to add or remove? - Can chronic treatment maintain benefits, or are effects temporary? - What are the long-term risks of manipulating blood factors? - Will human aging respond the same way mouse aging does?

The Biological Logic

Why would young blood rejuvenate old tissues?

The prevailing hypothesis: systemic signaling coordinates tissue maintenance across the body. Blood carries signals that tell tissues how to behave—grow, repair, quiesce, inflame.

In young animals, these signals promote regeneration and maintenance. Stem cells stay active. Repair mechanisms function well. Inflammation is controlled.

In old animals, the signaling environment shifts. Pro-inflammatory factors increase. Repair signals decrease. Stem cells become quiescent. The blood is telling tissues to shut down.

Tissues don't age in isolation. They age in a systemic context—bathed in blood that carries the biochemical signature of the whole organism's age. Change the blood, and you change the signals. Change the signals, and tissues respond.

This is actually hopeful. It suggests that old tissues haven't lost the capacity to regenerate. They've lost the signals to regenerate. The machinery is still there, waiting for the right instructions.

If we can send the right signals—through transfusion, dilution, or pharmacological intervention—maybe we can wake up dormant regenerative capacity in old tissues.

The Ethical Terrain

Parabiosis research raises uncomfortable questions.

The vampire problem: If young blood genuinely rejuvenates old bodies, who supplies the young blood? Healthy young people might not want to be regularly bled for the benefit of the elderly. Creating a market in young blood raises obvious concerns about exploitation.

The dilution solution: If plasma dilution works as well as young blood transfusion, this concern diminishes. You're not harvesting from the young; you're filtering the old.

Access and inequality: Longevity interventions will likely be expensive initially. Who gets access? Will life extension become another dimension of inequality—the rich living longer while the poor age normally?

Population effects: If people live significantly longer, what happens to resource consumption, career structures, inheritance, political leadership? Society is built around assumptions of human lifespan. Changing that changes everything.

These aren't reasons not to pursue the research. They're reasons to think carefully about how it's deployed if it works.

Where This Leads

Parabiosis research has revealed that aging is, in part, a systemic process mediated by circulating factors. Old tissues aren't irreversibly damaged—they're responding to an aged signaling environment.

This opens multiple therapeutic avenues: - Factor supplementation: Identify and administer the youthful signals - Factor removal: Identify and filter out the pro-aging signals - Plasma dilution: Periodically refresh the blood without needing young donors - Senescent cell clearance: Remove cells that produce harmful secretions

The blood is a communication network, and aging is partly a message. If we can edit the message, we might be able to change what tissues hear—and how they respond.

We're not there yet. But the parabiosis experiments have shown that the line between young and old is not as fixed as we thought. The blood carries information about age, and that information can be modified.

Whether this becomes therapy or remains laboratory curiosity depends on the next decade of research. But the principle is established: age is partly in the blood, and blood can be changed.

Further Reading

- Conboy, I. M. et al. (2005). "Rejuvenation of aged progenitor cells by exposure to a young systemic environment." Nature. - Villeda, S. A. et al. (2014). "Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice." Nature Medicine. - Mehdipour, M. et al. (2020). "Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin." Aging.

This is Part 6 of the Longevity series. Next: "Telomeres and the Hayflick Limit."