Blood Test to Detect Zombie Cells May Expand Use of Older Donor Hearts and Reduce Transplant Wait Times

Key Takeaways:

A new blood test detects “zombie” cells linked to heart aging using biomarkers GDF15 and p21.
It could help identify biologically healthy hearts from older donors previously considered ineligible.
If validated, the test may increase transplantable organs and shorten patient wait times.

Researchers are developing a blood-based test that could help identify which donor hearts from older individuals are biologically healthy, potentially expanding the pool of transplantable organs and offering new hope to patients waiting for a heart transplant.

Heart Failure

Currently, hearts from donors over 65 are often declined due to concerns about poorer outcomes. However, age alone doesn’t always reflect the true biological state of the heart, and promising new research suggests there may be a way to assess organ health at the molecular level.

Why Cellular Aging Matters in Heart Transplants

The focus of the study is on senescent cells, sometimes referred to as “zombie” cells which are cells that have stopped dividing and functioning normally but remain metabolically active. These cells can secrete a range of pro-inflammatory and tissue-damaging molecules, contributing to fibrosis, inflammation, and overall tissue decline.

In the context of heart transplantation, the presence of senescent cells can accelerate cardiac aging and reduce the likelihood that a donor heart will function well in a recipient. Yet not all older hearts contain high levels of these cells, and distinguishing between those that do and those that don’t has been a longstanding challenge.

GDF15 and p21: Two Key Biomarkers Under Investigation

The research team from Newcastle University, presenting at the British Cardiovascular Society Conference, identified two promising molecular markers that may serve as indicators of senescent cell activity: GDF15 and p21.

GDF15 (Growth Differentiation Factor 15) is a protein that is secreted by cells under stress and has been linked to both aging and cardiovascular disease. In laboratory studies, senescent heart cells consistently showed elevated levels of GDF15 compared to healthy cells.

To explore this further, researchers analyzed blood samples from 774 individuals aged 85 and older. Those with clinically diagnosed heart disease had significantly higher levels of GDF15, which supports the hypothesis that this protein is closely tied to cardiac aging.

In parallel, the team studied RNA from eight human donor hearts and found increased expression of p21, a gene associated with cellular aging and DNA damage response. Elevated p21 levels were found to correlate strongly with other established markers of cardiovascular dysfunction.

Building a Molecular Signature to Identify Healthier Hearts

Taken together, GDF15 and p21 may form the basis of a “senescence signature,” a biological fingerprint that could help clinicians determine whether a donor heart is biologically robust or showing signs of age-related damage at the cellular level.

“Our work sheds light on the clues left by senescent, or ‘zombie’, cells in the body,” said Dr. Gavin Richardson, the study’s lead investigator. “We are confident that we can use these markers to better understand which hearts, currently considered ineligible, could in fact be suitable for transplant.”

If validated, such a test could allow more donor hearts especially those from older individuals, to be safely used, potentially easing organ shortages and reducing wait times.

Challenges Ahead Before Clinical Use

While the findings are encouraging, several key questions remain. First, the data so far show correlation, not causation. It is not yet known whether high levels of GDF15 or p21 directly lead to worse transplant outcomes, or simply reflect general cardiac stress or aging.

Second, the population studied was primarily over 85 years old. It’s unclear how these biomarkers will perform in donors aged 65 to 75, the group most likely to benefit if eligibility criteria were updated based on biological rather than chronological age.

Third, integrating a biomarker test into the time-sensitive process of organ allocation could present operational challenges. Blood-based diagnostics would need to be rapid, reliable, and clinically validated before being used to influence transplant decisions.

Could Senolytic Therapies Offer Another Solution?

If zombie cells compromise organ quality, another avenue worth exploring is whether senolytic drugs, such as Dasatinib and Quercetin, could be used to eliminate these cells prior to transplantation, potentially rejuvenating organs rather than rejecting them based on biomarker levels alone.

More research is needed to understand whether such treatments are feasible or safe in the context of transplantation.

Next Steps and Broader Implications

The team is continuing its research using samples from large national transplant biobanks, including NHS Blood and Transplant and the Quality in Organ Donation (QUOD) initiative. The goal is to determine whether this molecular signature can predict real-world transplant outcomes, including graft survival and recipient health.

If successful, this approach could be extended beyond heart transplantation. Organs such as the liver, kidney, and lungs — where age-related decline is often difficult to assess quickly — may also benefit from a similar biomarker-driven evaluation.

For now, the research remains in its early stages, but it points to a future where the biological age of organs — not just the donor’s chronological age — guides critical transplant decisions.

The Bottom Line

Not all aging hearts are created equal — and this research could finally give us a way to tell the difference.

By tracking the chemical fingerprints left behind by “zombie” cells, scientists are moving closer to a future where donor hearts aren’t rejected just because of a birth date. If tests for markers like GDF15 and p21 prove reliable, they could unlock a hidden supply of healthy organs — and offer a second chance to people stuck waiting on transplant lists.

The science isn’t settled yet. Bigger trials and long-term outcome data are still needed. But if this approach holds up, it won’t just change how we assess hearts — it could rewrite the rules for organ donation entirely.

FAQs

What are “zombie” cells?
They are damaged, non-dividing cells that release harmful molecules and accelerate tissue aging.

Why are older donor hearts usually rejected?
They’re often excluded due to a higher risk of complications, even if the heart is still biologically healthy.

What does the new blood test detect?
It measures biomarkers like GDF15 and p21 linked to cellular aging in the heart.

Can this test be used now?
Not yet — it’s still in the research phase and needs more validation before clinical use.

How could this help transplant patients?
It may increase the number of usable donor hearts and reduce waiting times for recipients.