ROCHESTER, Minn. — Mayo Clinic researchers have estimated the risk that pancreatic cysts with worrisome or high-risk features will progress to pancreatic cancer or advanced precancerous changes within three years. The findings, published in Gastroenterology, could help physicians and patients better assess risk and make more informed decisions about whether to monitor a cyst or consider surgery. 

The prospective study found that risk increased with the number of worrisome features, or findings that the cyst needs closer monitoring. Patients whose cysts had one worrisome feature had about a 2% chance of developing pancreatic cancer or advanced precancerous changes within three years. The risk rose to 4% for those with two worrisome features and 18% for those with three or more. 

"This information will help us counsel patients. If we want to intercept pancreatic cancer while also sparing patients from unnecessary interventions, we must really know what is likely to become cancer and what is not," says Shounak Majumder, M.D., lead author and a gastroenterologist at Mayo Clinic.  

What does pancreatic cyst risk mean for patients?  

Pancreatic cysts are common and often discovered during imaging for an unrelated reason. Most do not become cancerous, but certain features seen on imaging can indicate a greater risk. Pancreatic cysts are classified as having high-risk features, worrisome features or neither. 

Pancreatic cysts without worrisome or high-risk features have a relatively low likelihood of progression to cancer. Cysts with high-risk features may prompt physicians to recommend surgery because of greater concern about cancer or advanced precancerous changes. Cysts with worrisome features often are monitored closely, although some may also require surgery.  

"Sometimes, we are unable to reliably determine whether a cyst will become pancreatic cancer or not," Dr. Majumder says. "That uncertainty creates a lot of anxiety for some patients undergoing surveillance, and some will opt for surgery." 

More precise estimates of progression risk can help patients and physicians weigh the potential benefits of surveillance and surgery.   

How did researchers determine pancreatic cancer risk?  

The study followed 230 people with pancreatic cysts that had worrisome or high-risk features. Unlike studies that look back at existing medical records or primarily include patients who underwent surgery, researchers enrolled participants and followed them over time, regardless of whether they chose surgery or surveillance. 

Of the 230 participants, 32 underwent surgery within the first three months after enrollment, and 198 entered clinical surveillance. Among those monitored, 185 had cysts with worrisome features, and 13 had cysts with high-risk features.  

The study found that patients with multiple worrisome features may represent a substantially higher-risk subgroup, while risk was not markedly elevated in patients with a single worrisome feature. 

Pancreatic cancers diagnosed among patients under careful surveillance were detected at a very early stage, suggesting that surveillance of appropriately risk-stratified patients may provide an opportunity to catch pancreatic cancer early. The finding suggests that regular surveillance may be an appropriate approach for some patients rather than immediate surgery. 

The three-year risk estimates also provide a benchmark for evaluating blood tests and designing studies of other approaches to early pancreatic cancer detection. 

Can blood tests and biomarkers predict pancreatic cancer risk? 

In a separate study led by Dr. Majumder and colleagues published in Clinical Gastroenterology and Hepatology, researchers examined CA 19-9, a blood biomarker that may be elevated in people with pancreatic cancer and is sometimes used to monitor pancreatic cysts. 

An elevated CA 19-9 result alone did not reliably predict which patients with pancreatic cysts would develop cancer. Among patients with low-risk cysts who had an elevated CA 19-9 level, none developed pancreatic cancer during the study's follow-up period. 

The findings suggest that a blood biomarker test should be considered with other information about a patient's health and cancer risk. They also underscore the need for new biomarker tests that can reliably detect the earliest stages of cancer in patients with pancreatic cysts. 

The data from these studies could help researchers design larger studies and clinical trials of new approaches to the early detection and prevention of pancreatic cancer as part of a broader effort at Mayo Clinic known as the Precure Research initiative.  

"The goal is more precise, personalized surveillance and an early detection approach that identifies patients who may benefit from earlier intervention while helping those at lower risk avoid unnecessary procedures and major surgery," says Dr. Majumder.  

For a complete list of authors, disclosures and funding, review the study.  

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu  

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PHOENIX — Mayo Clinic researchers have developed and externally validated an artificial intelligence (AI) model that can identify a potentially significant heart obstruction from routine ultrasound videos without relying on specialized Doppler imaging. The technology could help clinicians flag patients with hypertrophic cardiomyopathy (HCM) who may need additional testing, particularly in settings where specialized echocardiography expertise is limited. Study findings are published in Circulation: Cardiovascular Imaging.  

HCM is a genetic condition that causes the heart muscle to become abnormally thick. About two-thirds of these patients develop left ventricular outflow tract (LVOT) obstruction, which restricts blood leaving the heart, causing symptoms such as chest pain and shortness of breath with exertion or when lying flat. Knowing which patients develop LVOT obstruction is important because it influences treatment decisions and long-term management for patients with HCM. 

"Measuring LVOT obstruction typically requires Doppler echocardiography, which depends on precise ultrasound-beam alignment and operator expertise," says Imon Banerjee, Ph.D., an AI researcher at Mayo Clinic in Phoenix and senior author of the study. "We wanted to determine whether AI could recognize subtle patterns that are imperceptible to the human eye in routinely acquired B-mode ultrasound videos and identify patients with LVOT obstruction earlier, enabling timely confirmatory Doppler evaluation and referral when appropriate." 

The study included 1,833 patients in the Mayo Clinic cohort. The model was tested in 275 patients and externally validated in 46 patients from a hospital in South Korea. The AI model used only resting, non-Doppler ultrasound videos to predict whether a patient had a potentially significant obstruction to blood leaving the heart. Researchers found that combining information from three standard ultrasound views improved the model's ability to distinguish patients with elevated LVOT gradients. The model also helped identify obstruction that may only appear when the heart is under stress. 

The model maintained strong performance in the South Korean group despite substantial differences between that population and the patients used to develop the model, supporting further study of the technology across different patient populations and clinical settings.  

In a subset of cases, the AI model identified obstruction more accurately than two expert echocardiographers who reviewed the same non-Doppler images. The findings highlight how difficult it can be to recognize LVOT obstruction from routine two-dimensional images without Doppler measurements. 

"This technology is intended to complement, not replace, Doppler echocardiography," Dr. Banerjee says. "By enabling earlier identification of patients with potential LVOT obstruction, it could escalate timely detection and prompt confirmatory Doppler measurements, stress testing, or referral to an HCM specialty center. It also could support evaluation using portable ultrasound or in settings where comprehensive Doppler assessment may not be readily available, helping expand access to earlier screening and risk assessment." 

Dr. Banerjee notes that the next steps include additional prospective validation across broader clinical settings, ultrasound platforms and patient populations. 

The list of authors and disclosures may be found in the article, Beyond Doppler: Scalable AI Detection of LVOT Obstruction in HCM. This study received no external funding. 

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About Mayo Clinic 

Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contacts: 
 

• Terri Malloy, Mayo Clinic Communications, newsbureau@mayo.edu 

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ROCHESTER, Minn. — An international study led by Mayo Clinic researchers has identified interleukin-6 (IL-6) receptor blockers as a promising option for preventing relapses in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD is a rare autoimmune neurological disorder that can cause vision loss, paralysis and other serious neurological complications.

The study, published in JAMA Neurology, provides one of the largest real-world evaluations to date of IL-6 receptor blockade in patients with MOGAD and offers new evidence to help guide treatment decisions while randomized clinical trials are underway.

MOGAD occurs when the immune system mistakenly attacks myelin, the protective coating surrounding nerve fibers in the brain, spinal cord and optic nerves. In some patients, the disease causes repeated inflammatory attacks, or relapses, that can lead to accumulating neurological disability. Although several therapies are used off-label, there are currently no treatments approved specifically for preventing relapses in MOGAD.

The study focused on two medications, tocilizumab and satralizumab, that belong to a class of drugs known as IL-6 receptor blockers. Researchers believe the immune signaling protein IL-6 plays an important role in the inflammation that damages myelin in people diagnosed with MOGAD. By blocking that immune signaling pathway, these medications are designed to reduce inflammation and help prevent future relapses.

"Interleukin-6 receptor blockers appear to be a promising treatment option for people living with MOGAD," says Eoin Flanagan, M.B., B.Ch., a neurologist at Mayo Clinic and senior author of the study. "While we await results from randomized clinical trials, these findings provide additional evidence that these medications may help limit the neurological disability that can accumulate with repeated attacks.”

Researchers evaluated 116 patients treated with IL-6 receptor blockers across multiple centers in North and South America, making it the largest observational study of its kind. Most participants received tocilizumab, which is widely available around the world, while a smaller number received satralizumab. The study found that patients had substantially fewer relapses after starting treatment and that the medications had a generally favorable safety profile, though infections remain an important consideration for clinicians.

Because MOGAD is uncommon, individual medical centers often care for relatively small numbers of patients, making it difficult to study new treatments. This multinational collaboration allowed researchers to evaluate outcomes across various patient populations while expanding the evidence for IL-6 receptor blockade in MOGAD.

"Rare diseases require collaboration," says Andreu Vilaseca Jolonch, M.D., first author of the study and a neurology fellow at Mayo Clinic. "By bringing together patients and researchers across multiple countries, we were able to generate stronger evidence than any single center could produce alone. That collaboration not only strengthened this study but also created a foundation for future research."

Multiple clinical trials evaluating treatments for MOGAD are underway, and observational studies such as this one help provide important evidence while physicians await those results.

"There is growing optimism for patients with MOGAD," Dr. Flanagan says. "New treatments are emerging, and we're trying to bring the best treatment options to patients while continuing to learn which therapies work best."

This research was supported by the National Institutes of Health (R01NS113828). One patient included in the study was supported by National Institutes of Health grant R01AI170863-01A1.

 For a complete list of authors, disclosures and funding, review the JAMA Neurology article.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

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Organ transplantation has transformed countless lives, offering hope to people with end-stage organ failure. But for many patients, the journey doesn't end with surgery. Lifelong anti-rejection medications protect transplanted organs, but they also can increase the risk of infection, cancer and other serious health complications.

On the latest episode of "Tomorrow's Cure," host Lindsay Sievert explores a question researchers have pursued for decades: What if the immune system could be taught to accept a transplanted organ instead of suppressing it for life?

Joining the conversation are Timucin Taner, M.D., Ph.D., a transplant surgeon at Mayo Clinic, and Angus Thomson, Ph.D., DSc., a transplant immunologist at the University of Pittsburgh Medical Center. Together, they discuss how advances in immune tolerance and cell therapy are bringing researchers closer to that goal.

Rather than broadly suppressing the immune system, scientists are studying ways to selectively prevent it from attacking a donated organ while preserving its ability to fight infection and disease.

"We're talking about trying to retrain the immune system," says Dr. Taner. "Not just reduce the immune responses to anything, but reduce the immune responses to the organ itself."

Researchers believe the liver may hold important clues because of its unique ability to promote immune tolerance. Clinical trials at Mayo Clinic and other institutions are testing cell-based therapies designed to help the immune system recognize transplanted organs without triggering rejection. Although more research is needed, early findings offer reason for optimism and could one day benefit patients receiving liver, kidney, heart and lung transplants, as well as people living with autoimmune diseases.

Listen to the latest episode of "Tomorrow's Cure" to learn how Mayo Clinic leads innovation in transplant. You can also explore the show's full library of episodes and guests on the show's playlist.

The post How scientists hope to retrain the immune system after an organ transplant appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — Mayo Clinic researchers have developed an experimental drug with the help of artificial intelligence (AI) to target the "undruggable" PDZ-domain of GIPC1 protein that helps different types of cancer, including pancreatic cancer, to grow and resist treatment. In laboratory studies, the drug slowed tumor growth, improved survival and enhanced the effects of the chemotherapy drug gemcitabine.

The findings, published in Cell Reports, also demonstrate how AI could help develop a small molecule inhibitor of a target protein that can be less toxic and speed the discovery of new cancer treatments.

Pancreatic cancer is one of the most difficult cancers to treat because it is often diagnosed after it has spread and is resistant to many current therapies. While survival rates remain low, advances in research are creating new opportunities to develop more effective treatments. This study represents one of those promising advances, offering a potential new strategy for targeting pancreatic cancer.

Using AI, in collaboration with Sravathi AI Technology for IP Sharing, a company based in Bangalore, India, the research team screened nearly 40,000 potential compounds before identifying one that blocks GIPC1. The experimental drug also showed early signs of changing the environment around tumors in ways that could improve future combination therapies. Additional studies are needed before it can be tested in people.

"Pancreatic cancer has remained exceptionally difficult to treat because tumors rapidly adapt and become resistant to many available therapies," says Debabrata (Dev) Mukhopadhyay, Ph.D., senior author of the study and a cancer researcher at Mayo Clinic in Florida. "Our study demonstrates that AI can help us identify entirely new therapeutic opportunities against targets that have historically been considered undruggable. While these findings are preclinical, they provide a strong foundation for the next phase of research."

The therapy remains experimental, and additional studies are needed to evaluate its safety and determine whether it can advance to clinical trials.

This research was supported in part by the National Institutes of Health, the Florida State Fund for the Casey DeSantis Cancer Research Program and the U.S. Department of Defense. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — Mayo Clinic researchers have identified a protein that cancer cells use to shut down the body's immune response, a discovery that could help scientists develop new treatments that make cancer immunotherapies more effective.

Published in the Journal of Clinical Investigation, the study identifies a previously unknown role for a protein called TRAILshort, which acts like an immune "off switch." The researchers found that TRAILshort prevents T cells — the immune system's primary cancer-fighting cells — from recognizing and destroying cancer and virus-infected cells. In preclinical models, blocking the protein restored T-cell activity and improved immune response. 

The researchers also found that TRAILshort reduces the effectiveness of chimeric antigen receptor-T cell therapy (CAR-T cell therapy), one of the most advanced forms of cancer immunotherapy. Their findings suggest that therapies designed to block TRAILshort could improve CAR-T treatment and potentially benefit other immune-based cancer therapies.

"What strikes me most is that TRAILshort appears in cancer, HIV, COVID-19, tuberculosis, lupus and Crohn's disease — almost every condition where the immune system is failing or misfiring. That tells us we may have identified a fundamental switch in human immunity, not just a curiosity in one disease," says Andrew Badley, M.D., senior author of the study. Dr. Badley is the HH Sheikh Khalifa Bin Zayed Al Nahyan Professor of Infectious Diseases and an immunologist at Mayo Clinic.

How cancer disrupts the immune response 

Mayo Clinic researchers first discovered TRAILshort while studying HIV nearly 15 years ago. In 2020, they found that cancer cells also produce the protein, but how it suppressed T-cell activity remained unknown. This new study reveals the mechanism for the first time.

Researchers found elevated levels of TRAILshort in melanoma, lung, breast, pancreatic and ovarian cancers, as well as Hodgkin lymphoma. Elevated levels also were found in infectious diseases, including COVID-19, tuberculosis and hepatitis C.

Using highly specific antibodies and engineered preclinical models, the team found that TRAILshort activates SHP-1, a protein that acts as a molecular brake, shutting down T cells before they can attack diseased cells.

"This is the first study to show that TRAILshort doesn't just block cell death — it also acts as a signaling molecule that directly suppresses T-cell activity," says Shahrzad Jalali, Ph.D., a research scientist at Mayo Clinic and lead author of the study. "That reveals an entirely new role for the protein in regulating the immune response."

Why TRAILshort is a potential target for new therapies

The findings suggest several potential therapeutic applications.

Researchers found that TRAILshort significantly reduced CAR-T therapy's ability to control tumors in preclinical models. Blocking the protein restored immune activity, suggesting that targeting it could be a new strategy to improve CAR-T therapy and other immunotherapies. The researchers also believe that TRAILshort could serve as a biomarker to help identify tumors more likely to respond to targeted therapies.

"Discovering the role of TRAILshort and how it inhibits CAR-T cells opens the door for a new therapeutic strategy to improve their activity," says Saad Kenderian, M.B. Ch.B., an oncologist at Mayo Clinic Comprehensive Cancer Center and study co-author. "This is an important step as we work to make CAR-T therapy more effective for patients with cancer."

Beyond cancer, researchers say TRAILshort  may eventually provide a way to selectively reduce harmful immune activity in autoimmune diseases or transplantation without broadly suppressing the immune system.

"In cancer, there's too much TRAILshort, so our goal is to get rid of it with antibodies that remove it. In autoimmune disease, there's not enough TRAILshort, so our goal is to deliver more," Dr. Badley says.

Additional studies are needed to determine whether these approaches are safe and effective in patients.

"What excites us most is that this discovery gives us a new, actionable way to regulate the immune system," Dr. Badley says. "By targeting TRAILshort, we may be able to strengthen immune responses against cancer and chronic infections or, in other diseases, reduce harmful immune activity."

This research is part of a broader effort at Mayo Clinic known as the Precure Research initiative. It focuses on developing tools to help clinicians detect and address disease-related changes earlier, before symptoms appear or conditions become harder to treat. This discovery identifies the molecular mechanism behind T-cell failure across cancer and chronic infection, giving researchers a defined target and a road map for therapeutic development.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About Mayo Clinic Comprehensive Cancer Center
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — A visit from a therapy animal may do more than lift spirits. A new study in Mayo Clinic Proceedings highlights how animal-assisted treatment can support inpatient stroke rehabilitation. Patients who interacted with therapy animals showed greater engagement in their treatment, increased physical activity and longer mobility compared with those who did not.

The findings suggest a promising approach to addressing common barriers patients face with stroke recovery, including limited motivation, reduced energy, lack of companionship and decreased interest in therapy activities. By incorporating trained therapy dog-handler teams into rehabilitation care, patients can do a variety of activities including walking, playing fetch, and petting or brushing the dog.

"The presence of a therapy dog can change the entire dynamic of a rehabilitation session," says Whitney Romine, manager of animal-assisted services at Mayo Clinic. "Patients often share that they feel more grounded, safe and empowered to engage in therapy activities, which can make a meaningful difference in their recovery experience."

The paper, "The Impact of Animal-Assisted Treatment on Inpatient Stroke Rehabilitation," shows how patient care could be improved using a clinical care delivery model that includes qualified animal handler teams. The study also explores how these changes could be applied across a variety of medical specialties and patient populations.

"Stroke recovery can be challenging, particularly when patients face barriers such as low motivation or limited energy," says Brent Bauer, M.D., a physician in internal medicine at Mayo Clinic. "This research demonstrates that animal-assisted treatment may offer a practical and effective way to enhance engagement and support better rehabilitation outcomes."

Watch: Dr. Brent Bauer discusses the benefits of therapy dogs

Journalists: Sound bites and broll with Dr. Bauer are in the downloads at the end of the post. Please courtesy: "Brent Bauer, M.D./General Internal Medicine/Mayo Clinic."

This research was conducted in collaboration with Nestlé Purina PetCare. For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic Proceedings
Mayo Clinic Proceedings is a peer-reviewed medical journal that publishes original research and reviews across clinical and translational science.

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — A series of Mayo Clinic studies is helping reshape scientists' understanding of senescent, or "zombie," cells — aging cells that no longer divide but remain metabolically active and release inflammatory molecules that contribute to age-related diseases.

Published across Nature journals, the studies authored by scientists within the Robert and Arlene Kogod Center on Aging move the field beyond recognizing that senescent cells contribute to aging. Together, they provide new tools to identify these cells, uncover mechanisms that drive inflammation and explore strategies to reduce their effects in preclinical models. In collaboration with researchers across the U.S., they are part of an ambitious project to map senescent cells across different tissues. The project is called the Cellular Senescence Network (SenNet) Consortium and is funded by the National Institutes of Health Common Fund. Its primary objective is to compile comprehensive atlases of senescent cells within the human body over a lifetime.  

"This body of work is moving the aging field forward to precisely identify, understand and target the specific senescent cells that contribute to age-related dysfunction, which is the necessary groundwork to develop new therapies that support healthy aging," says Marissa Schafer, Ph.D., a Mayo Clinic researcher whose laboratory led several of the studies.

Exploring new therapeutic strategies

Several studies evaluated approaches designed to reduce the burden or harmful effects of senescent cells in preclinical models.

The research examined interventions, including senolytic drugs, a naturally occurring compound found in tomatoes, and genetic approaches that selectively target senescent cells. In aged mice, these strategies reduced measures of inflammation and improved outcomes associated with aging, including physical frailty, brain inflammation and cognitive performance.

Another study identified IL-23R as a potential blood biomarker that could one day help researchers assess biological aging and monitor responses to future therapies.

Although additional research is needed before these findings can be translated to patient care, the studies provide a stronger scientific foundation for developing more targeted interventions for age-related diseases.

Dr. Schafer is the senior author of the following papers:

• "IL-23R is a senescence-linked circulating and tissue biomarker of aging"
• "Spatial mapping and senolytic targeting of senescent and disease-associated microglia in aged mouse brain white matter"

Revealing why senescent cells drive inflammation

Additional studies uncovered previously unknown mechanisms that help explain why senescent cells produce persistent inflammation.

Researchers found that dysfunctional mitochondria — the structures that generate energy inside cells — contribute to inflammation through multiple pathways. One mechanism involves mitochondrial DNA and RNA activating immune signaling. Another shows that mitochondrial metabolism changes how inflammatory genes are activated through epigenetic regulation.

Together, these discoveries identify potential therapeutic targets that could reduce harmful inflammation without necessarily eliminating senescent cells.

João Passos, Ph.D., is the senior author of the following papers:

• "Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues"
• "Mitochondrial metabolism and epigenetic crosstalk drive SASP"
• "Mitochondrial RNA cytosolic leakage drives the SASP"

A growing body of research

Taken together, these studies advance the field from demonstrating that senescent cells contribute to aging toward understanding which senescent cells matter most, how they drive disease and how they may be targeted more precisely.

Rather than focusing solely on eliminating senescent cells, the research supports a more nuanced approach that aims to identify the biological pathways responsible for harmful inflammation and develop therapies that selectively interrupt those processes.

Darren Baker, Ph.D., a Mayo Clinic researcher, is the senior author of the paper, "Senotypes define the diverse landscape of senescent cells."

The research is part of a larger effort at Mayo Clinic called the Precure Research initiative, which is focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the studies for a complete list of authors, disclosures and funding.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic research advances understanding of senescent ‘zombie’ cells, healthy aging appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Researchers have uncovered a previously unknown mechanism that helps aging cells drive the chronic inflammation linked to many age-related diseases. The findings reveal how dysfunctional mitochondria — the cell's energy-producing structures — work with the cell's epigenetic machinery to switch on inflammatory genes, opening the door to a new therapeutic approach for promoting healthier aging.

The study, published in Nature, builds upon years of research showing that senescent, or "zombie," cells accumulate with age. While these cells no longer divide, they remain metabolically active and release a cocktail of inflammatory molecules known as the senescence-associated secretory phenotype, or SASP.

This persistent inflammation is thought to contribute to frailty, cardiovascular disease, cancer, neurodegeneration and other disorders of aging.

"For years, the field has focused on getting rid of senescent cells," says João Passos, Ph.D., a Mayo Clinic researcher and senior author of the study conducted in collaboration with Sanford Burnham Prebys Medical Discovery Institute. "Our strategy has been different. Instead of killing the cells, we asked whether we could switch off the inflammation that makes them harmful."

Previous work from the Passos laboratory demonstrated that damaged mitochondria leak mitochondrial DNA and RNA into the cell, activating immune pathways that trigger inflammation. The new study identifies a second, independent pathway that is equally essential.

"We found that inflammatory signaling alone isn't enough," says Helene Martini, Pharm.D., Ph.D., a Mayo Clinic researcher and first author of the study. "The cells also need a metabolic signal from mitochondria that changes how inflammatory genes are turned on."

The researchers discovered that senescent cells increase production of acetyl-CoA, a molecule generated through mitochondrial metabolism. Acetyl-CoA enables epigenetic modifications — chemical changes that regulate whether genes are switched on or off without altering the DNA sequence itself. These modifications make inflammatory genes more accessible, allowing them to be robustly expressed.

In other words, mitochondrial DNA and RNA provide the inflammatory alarm, while mitochondrial metabolism grants the molecular "permission" needed to fully activate inflammatory genes.

"This is a completely new pathway," says Dr. Martini. "We found that dysfunctional mitochondria can promote inflammation by controlling epigenetic switches that turn inflammatory genes on."

The team also identified a promising therapeutic target: a mitochondrial citrate transporter known as SLC25A1. Blocking this transporter reduced the supply of acetyl-CoA, limiting activation of inflammatory genes even though the initial immune signals remained present. Together, these findings reveal a previously unrecognized control point that could be exploited to promote healthier aging.

The research is part of a larger effort at Mayo Clinic called the Precure Research initiative, which is focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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PHOENIX — An international phase 3 study performed at all three Mayo Clinic destination medical centers found that a new immunotherapy helped many patients with an aggressive form of bladder cancer keep their bladder instead of having it surgically removed. The treatment also kept many patients cancer-free for more than two years and caused mostly mild side effects. The findings were published in The Lancet Oncology.

Patients in the study had high-risk bladder cancer that had returned despite standard treatment with bacillus Calmette-Guérin (BCG). For these patients, surgery to remove the bladder is typically the recommended next step. The new immunotherapy treatment, called cretostimogene grenadenorepvec, produced a complete response, with no detectable signs of cancer in 75% of patients, with many of those responses lasting beyond two years.

"Until now, patients whose cancer returned after BCG therapy have had few effective options besides bladder removal," says Mark Tyson II, M.D., lead author of the study and a urologist at Mayo Clinic in Arizona. "This study shows we may be able to offer many of those patients another option without compromising cancer control."

Among patients whose cancer completely disappeared after treatment, about 60% remained cancer-free two years later. In one patient, the cancer has not returned for more than four years after completing treatment. Most treatment-related side effects were mild, temporary bladder symptoms, and researchers reported no severe treatment-related side effects.

"For patients, this isn't just about treating cancer — it's about preserving quality of life," says Dr. Tyson. "Avoiding bladder removal can have a profound impact on daily living. Seeing patients remain cancer-free for years while keeping their bladder is exactly the outcome we've been hoping to achieve."

The study included 115 patients treated at 41 medical centers across North America, Asia and Australia. Two years after starting treatment, an estimated 81% of patients had not needed surgery to remove their bladder. The researchers concluded that cretostimogene grenadenorepvec could become an important bladder-sparing treatment option for patients whose high-risk bladder cancer has returned after standard BCG therapy. They also noted that the treatment has not been directly compared with other bladder-sparing therapies in clinical trials.

The study was funded by CG Oncology. For a complete list of authors, disclosures and funding, review the study. The therapy remains investigational.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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