ARPA-H Awards $144 Million to Accelerate Human Healthspan Trials Targeting Aging Biology
核心洞察
ARPA-H (搜索)'s PROSPR program is funding seven research teams with up to $144 million over five years to develop interventions that extend healthspan by treating aging (搜索) as a tractable biological process.
The initiative aims to identify early biomarkers that can serve as surrogate endpoints to demonstrate therapeutic efficacy within one to three years, addressing the challenge of lengthy conventional aging (搜索) trials.
University of Rochester received up to $22 million to test TPN-101, an HIV drug repurposed to suppress retrotransposon activity and reduce age-related inflammation in a 200-participant clinical trial.
The US government is making an unprecedented investment in aging (搜索) research, with the Advanced Research Projects Agency for Health (ARPA-H (搜索)) committing up to $144 million to seven research teams working to prove that intervening in the biological processes of aging can help people stay healthier for longer. Through its PROSPR (Proactive Solutions for Prolonging Resilience) program, the agency is funding projects that span from biotech companies to leading academic institutions, all focused on extending healthspan—the years people live in good health.
Addressing the Clinical Trial Challenge in Aging Research
The initiative tackles one of the fundamental obstacles that has limited clinical development in geroscience: aging (搜索) is slow, and its associated diseases can take years or decades to emerge, making conventional trials unwieldy and expensive. PROSPR aims to use longitudinal human data to identify early, actionable biomarkers that respond before late-stage outcomes appear, serving as surrogate endpoints that can demonstrate within one to three years whether an intervention is shifting an individual's trajectory toward better function, resilience, and quality of life.
"PROSPR represents a tectonic shift in how we study healthy aging (搜索)," said ARPA-H (搜索) Director Dr Alicia Jackson. "ARPA-H will push the envelope on new biomarkers, interventions, and clinical trial designs that bring us closer to therapies that can help all Americans stay healthier for longer."
Major Biotech Recipients Target Key Aging Pathways
Among the funded projects, longevity biotech Cambrian BioPharma (搜索) received up to $30.8 million to support human trials of a daily, oral, next-generation rapamycin analog designed to selectively inhibit mTORC1 (搜索). The company views dysregulated mTORC1 signaling as a key driver of metabolic decline that accumulates with age and is tying its program to "intrinsic capacity," a composite measure of physical and metabolic resilience that declines over time.
"We founded Cambrian to lay the groundwork for treating some of today's most debilitating diseases at the molecular level, before they cause disease," said Cambrian CEO James Peyer. "Improving intrinsic capacity is the perfect expression of that mission, yet no drug development effort has ever attempted to target it."
Linnaeus Therapeutics (搜索) secured up to $22 million to advance a drug targeting the G protein-coupled estrogen receptor (GPER (搜索)) into human trials for healthspan preservation. The company is building on its oncology work, where more than 100 cancer (搜索) patients have been treated with its drug (LNS8801) in early human trials, with signals observed suggesting potential translation into aging (搜索)-related benefits.
University of Rochester Targets DNA-Triggered Inflammation
The University of Rochester received up to $22 million over five years to test whether TPN-101, a drug originally developed to treat HIV, can suppress retrotransposon activity and reduce biological aging (搜索). The project is led by Vera Gorbunova, the Doris Johns Cherry Professor in the Department of Biology and codirector of the Rochester Aging Research Center.
The research focuses on retrotransposons (搜索), virus-like sequences that make up a large portion of the human genome. Research by Gorbunova and colleagues has shown that retrotransposons become increasingly active with age, leading to inflammation that contributes to tissue decline. As people grow older, their cells begin to mistake parts of their own genetic material for viral threats, triggering chronic inflammation that contributes to physical and cognitive decline.
"When we are young, our cells are good at keeping retrotransposons (搜索) suppressed," Gorbunova explained. "As we age, that control weakens, and the immune system begins to respond as if the body is under viral attack."
The clinical phase will enroll 200 healthy adults ages 60 to 65, who will receive either TPN-101 or a placebo for 48 weeks. Researchers will assess changes in intrinsic capacity, including mobility, cognition, vitality, sensory function, and psychological health, along with molecular markers of biological aging (搜索), physical performance, and overall health.
Academic Institutions Contribute Infrastructure and Validation
Stanford University received funding for work to harmonize existing datasets collected across institutions to generate a healthspan score and test its accuracy in a one-year lifestyle intervention supported by an in-home digital assessment technology platform. The University of Texas Health Science Center (搜索) at San Antonio will pursue a regulatory path for testing therapeutics for aging (搜索) by running a phase 3 hybrid trial that repurposes three FDA-approved drugs—an SGLT2 inhibitor, rapamycin, and semaglutide—into a trial structure explicitly oriented around aging-related outcomes.
Columbia University's Mailman School of Public Health will analyze multiple previously conducted intervention trials to identify biomarkers that change with interventions tied to improved aging (搜索) outcomes.
Building Clinical Infrastructure for Future Trials
ARPA-H (搜索)'s stated intent extends beyond generating data on specific therapies to building the clinical infrastructure that would make future healthspan trials faster to design, easier to fund, and more credible to regulators and clinicians. The funding is structured as contracts rather than traditional grants, with funding levels varying by team and tied to the achievement of key milestones over five years.
"I built PROSPR because I kept seeing the same story play out: brilliant scientists uncover exciting ways to target the biology of aging (搜索) in animal models, only to have those ideas sit on the shelf because there's no clear path to test them in humans," said PROSPR Program Manager Dr Andrew Brack. "I wanted to change that."
The initiative represents one of the first comprehensive efforts to test interventions aimed directly at the biological mechanisms of aging (搜索), potentially reshaping how medicine approaches major health challenges associated with an aging population.