UConn Center on Aging is Part of a National Research Consortium Testing a Drug Originally Developed for HIV Treatment as a New Possible Gerotherapeutic Therapy for Biological Aging
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UConn Center on Aging is contributing its expertise to a national research consortium led by the University of Rochester investigating a newly identified biological driver of aging.
The major research effort is being supported by up to a $22 million contract from the Advanced Research Projects Agency for Health (ARPA‑H). ARPA-H is 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 multi‑institutional, national effort will explore whether using a drug originally developed to treat HIV can help reduce chronic, DNA‑triggered inflammation to help older adults maintain health, mobility, and cognitive function as they age.
The innovative initiative being led by the University of Rochester brings together researchers from institutions across the country, including Brown University, the University of Connecticut, The University of Texas Medical Branch (UTMB), UTHealth Houston, the University of Nebraska, and Transposon Therapeutics, all of which were selected by ARPA-H's PROactive Solutions for Prolonging Resilience (PROSPR) program.
The research teams at Rochester, led by Professor Vera Gorbunova, and Dr. John Sedivy at Brown, have identified retrotransposons-virus‑like genetic (LINE-1) elements that become more active with age-as a key contributor to chronic inflammation. As people grow older, their cells can mistakenly interpret fragments of their own DNA as viral threats, activating immune responses normally used to fight infections. This persistent "false alarm" may accelerate biological aging and contribute to diseases such as cancer, neurodegeneration, diabetes, and autoimmune conditions.
Gorbunova said the opportunity to test an intervention aimed directly at the biology of aging represents a significant step forward. "Our hope is that by dialing down retrotransposons, we can help people remain healthier, stronger, and mentally sharper as they age," she said. "That would be a profound shift in how we think about aging and intervention."
The ARPA‑H project will test whether TPN-101, an antiviral drug, can suppress retrotransposon activity and reduce this inflammation. Earlier studies suggest that blocking these pathways may improve cellular health and physical resilience. The new effort will expand those findings into long‑term preclinical studies and a randomized clinical trial.
The clinical trial, led by collaborators at Rochester, will enroll 200 adults aged 60 to 65 at the three clinical trial sites including at the University of Rochester, the UConn Center on Aging, and the University of Texas. The trial will evaluate how sustained treatment affects mobility, cognition, vitality, and other components of intrinsic capacity defined by the World Health Organization. Researchers will also examine physical performance, molecular markers of aging, and overall health outcomes.
"This gerotherapeutic drug research approach is cutting-edge and represents team science at its best. U.S. researchers are coming together for a very high-priority health issue for targeting biological aging. We are now able to aggressively accelerate the research timeline to move our latest research findings from the laboratory bench toward early clinical trial drug testing in a very short period of time," applauds Dr. George Kuchel, director of the UConn Center on Aging at the University of Connecticut who together with Dr. Iman Al-Naggar from the UConn Center on Aging and Dr. Chia-Ling Kuo is proud for UConn to be sharing its expertise of bringing effective drugs tested in the laboratory to the patient's bedside. "This research is very ambitious and exciting. UConn is thrilled to be a part of this innovative research collaboration aiming to slow biological aging and ultimately help older adults as they age maintain their health, function, and independence."
"We have known for years that non-infection related inflammation increases with age and is linked to poor aging outcomes," said Dr. Andrew Brack, ARPA-H Program Manager and creator of the PROSPR program. "Because LINE-1 retrotransposons have recently been reported to increase inflammation as we age, we are excited about the possibility that antiretroviral therapies, which have the added benefit of a long history of safety in non-diseased populations, will extend health span."
Kuchel of the UConn Center on Aging and his team agrees.
"Our biggest hope is to help our older adults prevent the onset of age-related diseases to extend their healthspan," says Kuchel.
"I am really excited about what we hope to achieve through these studies. Using the World Health Organization's framework of intrinsic capacity as an endpoint and as an ICD-11 (International Classification of Diseases) code is a great step towards identifying drugs that can help maintain or improve function and support healthy aging and well-being late into life," shares Al-Naggar of the UConn Center of Aging who is also assistant professor of cell biology at UConn School of Medicine.
