{"id":695032,"date":"2026-02-24T11:04:28","date_gmt":"2026-02-24T16:04:28","guid":{"rendered":"https:\/\/www.rochester.edu\/newscenter\/?p=695032"},"modified":"2026-02-24T14:12:25","modified_gmt":"2026-02-24T19:12:25","slug":"arpa-h-funding-retrotransposons-aging-695032","status":"publish","type":"post","link":"https:\/\/www.rochester.edu\/newscenter\/arpa-h-funding-retrotransposons-aging-695032\/","title":{"rendered":"URochester researchers awarded up to $22M to study a hidden driver of aging"},"content":{"rendered":"

The ARPA-H\u2013funded collaboration will test whether reducing DNA-triggered inflammation can help older adults stay healthier for longer.<\/h2>\n

What if people could stay healthier, stronger, and mentally sharper as they grow older\u2014not by treating diseases one by one but by slowing a biological process that drives aging itself? A new University of Rochester<\/a>\u2013led research effort will test whether a drug originally developed to treat HIV can quiet a chronic immune response triggered by the body\u2019s own DNA, to help preserve overall health and function later in life.<\/p>\n

The project is supported by a contract of up to $22 million over five years from the Advanced Research Projects Agency for Health<\/a> (ARPA-H), a federal agency created to support high-impact biomedical projects that could lead to transformative advances in health. Its highly competitive awards are designed to accelerate bold ideas that, if successful, could reshape how medicine approaches major health challenges. The URochester team is one of several selected by the agency\u2019s PROactive Solutions for Prolonging Resilience (PROSPR) program.<\/p>\n

The URochester effort is led by Vera Gorbunova<\/a>, the Doris Johns Cherry Professor in the Department of Biology<\/a> and currently codirector of the Rochester Aging Research (RoAR) Center<\/a> and the Upstate NY Comparative Biology of Aging Nathan Shock Center<\/a>, and \u00a0brings together URochester researchers Andrei Seluanov<\/a> from the River Campus, Kathi Heffner<\/a> from the School of Nursing<\/a> and codirector of the University\u2019s Resilience Research Center<\/a>, and Annette Medina-Walpole<\/a> from the Medical Center<\/a>, along with collaborators from Brown University, University of Connecticut, The University of Texas Medical Branch, University of Texas Health Houston, University of Nebraska, and Transposon Therapeutics.<\/p>\n

\u201cAging underlies many chronic diseases, but it\u2019s rarely targeted directly,\u201d Gorbunova says. \u201cThis project builds on the University of Rochester\u2019s long-standing leadership in aging research and gives us a unique opportunity to partner with other leading institutions to address one of the root causes of age-related decline.\u201d<\/p>\n

While scientists know that aging underlies many chronic diseases, the mechanisms driving this decline are poorly understood. One of the drivers may be hidden in our DNA: As people grow older, their cells can begin to mistake parts of their own genetic material for viral threats, triggering chronic inflammation that contributes to physical and cognitive decline.<\/p>\n

The project\u2014one of the first and most comprehensive efforts to test an intervention aimed directly at the biological mechanisms of aging\u2014will test whether this internal \u201cfalse alarm\u201d can be safely reduced, helping older adults stay healthier for longer.<\/p>\n

\u201cThe work being led by Professor Gorbunova is an excellent example of the ways in which large-scale public and private partnerships can address some of the most pressing challenges of human health and well-being,\u201d says University President Sarah Mangelsdorf. \u201cWe\u2019re grateful to Congress and our delegation, in particular, for their continued support of ARPA-H and the high-impact, transformative research it funds. We deeply appreciate ARPA-H and its recognition of Professor Gorbunova\u2019s research and of the University of Rochester\u2019s leadership in biomedical science and its application to human health.\u201d<\/p>\n

A hidden driver of aging<\/strong><\/h3>\n

The research focuses on retrotransposons, virus-like sequences called selfish genetic elements that make up a large portion of the human genome. Unlike actual viruses, transposons cannot exit the cell and infect other cells, but they seek to propagate themselves within the host DNA. Transposons are normally kept dormant, but research over the past decade by Gorbunova and her colleagues has shown that retrotransposons become increasingly active with age, leading to inflammation that contributes to tissue decline.<\/p>\n

\u201cWhen we are young, our cells are good at keeping retrotransposons suppressed,\u201d Gorbunova says. \u201cAs we age, that control weakens, and the immune system begins to respond as if the body is under viral attack.\u201d<\/p>\n

This kind of persistent, age-related immune response has been linked to a wide range of age-related diseases, such as neurodegeneration, cancer, diabetes, and autoimmune diseases. Gorbunova\u2019s lab was among the first to show that LINE-1 retrotransposons can directly activate interferon signaling<\/a>\u2014the same antiviral defense system cells use to detect viral infections\u2014creating a \u201cfalse alarm\u201d in the form of age-related inflammation.<\/p>\n

\u201cWe have known for years that non-infection related inflammation increases with age and is linked to poor aging outcomes,\u201d says Andrew Brack, ARPA-H program manager and creator of the PROSPR program. \u201cBecause LINE-1 retrotransposons have recently been reported to increase inflammation as we age, we are excited about the possibility that anti-retroviral therapies, which have the added benefit of a long history of safety in non-diseased populations, will extend healthspan.\u201d<\/p>\n

From discovery to intervention<\/strong><\/h3>\n

Building on those discoveries, the ARPA-H\u2013funded project will test whether a drug originally developed to treat HIV can suppress retrotransposon activity and reduce biological aging. The drug, TPN-101, inhibits reverse transcriptase\u2014an enzyme that retrotransposons rely on to replicate.<\/p>\n

In earlier preclinical studies, similar drugs reduced interferon signaling and chronic inflammation associated with aging. The new project will extend that work by testing long-term treatment in animal models, followed by a randomized clinical trial in humans. Heffner will lead the clinical trial.<\/p>\n

\u201cTranslating the Gorbunova Lab\u2019s pioneering discoveries into human clinical trials is an extraordinary opportunity to turn fundamental aging science into therapies that could meaningfully improve health in later life,\u201d says Heffner, who collaborates with Gorbunova and Seluanov on the executive committee of the University\u2019s Aging Institute, led by Medina-Walpole.<\/p>\n

The clinical phase of the study will enroll 200 healthy adults ages 60 to 65, who will receive either TPN-101 or a placebo for 48 weeks. The researchers will assess changes in intrinsic capacity, a World Health Organization framework that includes mobility, cognition, vitality, sensory function, and psychological health, along with molecular markers of biological aging, physical performance, and overall health.<\/p>\n

The study could help pave the way for therapies designed to preserve overall health and function as people grow older.<\/p>\n

\u201cOur hope is that by dialing down retrotransposons, we can help people remain healthier, stronger, and mentally sharper as they age,\u201d Gorbunova said. \u201cThat would be a profound shift in how we think about aging and intervention.\u201d<\/p>\n

Elected officials applaud landmark award<\/strong><\/h3>\n

Elected officials praised the award as a major investment in biomedical innovation and a recognition of URochester\u2019s leadership in aging research.<\/p>\n

US Senator Charles Schumer<\/strong>: \u201cURochester\u2019s scientific advancement is recognized around the globe and is an integral part of maintaining America\u2019s leadership in discovering new medical breakthroughs to advance human health. This $22 million ARPA-H award is an exciting opportunity for URochester, and I will continue to fight to bring new federal investment to advance this groundbreaking work.\u201d<\/p>\n

US Senator Kirsten Gillibrand: <\/strong>\u201cAs ranking member of the Senate Special Committee on Aging, I\u2019m pleased to see vital health and science investments addressing some of our most pressing challenges to healthy aging and longevity. This collaboration has the potential to address linkages between aging and chronic illnesses, as well as inform treatments to allow people to live longer, healthier lives. Congratulations to Dr. Gorbunova and the University of Rochester for this tremendous award, I look forward to the outcomes of this effort and continued leadership in aging research.\u201d<\/p>\n

Congressman Joe Morelle: <\/strong>\u201cThe University of Rochester is one of the world\u2019s leading universities in scientific discovery, so it is no surprise to me that they\u2019ve once again been chosen to spearhead a new, cutting-edge research initiative. Congratulations to Dr. Gorbunova and the entire University of Rochester team on this achievement, and as Vice Ranking Member of the House Appropriations Committee, I\u2019m going to continue working to secure more opportunities like this for our researchers, students, and innovators in our community.\u201d<\/p>\n

Congresswoman Claudia Tenney: <\/strong>\u201cThe University of Rochester plays a critical role in supporting hospitals and healthcare providers that serve patients across NY-24, and ARPA-H awarding this grant will have tangible, local impact. This investment strengthens our regional health care system, supports high-skilled medical and research jobs, and helps ensure that patients in our communities benefit from cutting-edge advances developed here in Upstate New York.\u201d<\/p>\n

Congressman Nick Langworthy:<\/strong> \u201cThis landmark ARPA-H award is a powerful vote of confidence in the University of Rochester\u2019s leadership in biomedical research and its ability to turn cutting-edge scientific ideas into real-world health breakthroughs. I was proud to support ARPA-H funding as part of the FY26 minibus the House passed that is making projects like this possible. Research that targets the underlying drivers of aging has the potential to transform how we approach chronic disease, improve quality of life for our seniors, and keep the United States at the forefront of medical innovation, all while reinforcing the University\u2019s role as a national hub for life-saving science and workforce talent.\u201d<\/p><\/blockquote>\n","protected":false},"excerpt":{"rendered":"

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