The US Advanced Research Projects Agency for Health (ARPA-H) announced the selection of seven research teams under its PROactive Solutions for Prolonging Resilience (PROSPR) program, an initiative designed to develop therapeutics and tools aimed at extending healthspan by targeting the biological drivers of aging.

The program marks one of the first coordinated federal efforts to directly intervene in aging processes rather than treating individual chronic diseases after onset. Despite increases in life expectancy, more than 90% of US adults aged over 65 live with at least one chronic condition, while around 80% have two or more, highlighting the growing gap between lifespan and years lived in good health. PROSPR will fund multidisciplinary academic and industry teams to identify early-stage biological markers of aging and develop interventions that can modify these pathways before functional decline or disease manifests. The initiative is also expected to support the first clinical trials explicitly designed to measure whether therapeutic intervention can improve long-term resilience and functional health in aging populations.

A central challenge in geroscience drug development has been the slow progression of aging, which makes traditional clinical endpoints, such as disease incidence or disability, impractical for evaluating candidate therapies. To address this, PROSPR aims to leverage longitudinal human datasets to identify early-responding biomarkers that could serve as surrogate endpoints, enabling clinical trials to assess intervention impact within one to three years.

Projects supported under the program include studies investigating chronic DNA-triggered inflammation as a driver of age-related decline, as well as trials evaluating repurposed therapeutics originally developed for other indications, such as antiviral agents, for their potential to preserve mobility, cognitive function, and overall resilience in older adults.

ARPA-H has committed up to USD 144 million over five years to the initiative, which agency leadership describes as funding rather than grants, “contingent upon each team meeting aggressive research milestones”. The seven recipients are:

  • Stanford University will harmonize existing health datasets to generate a healthspan score (PROSPR-IC score), and test the accuracy and utility of this score as a guide for interventions over one year
  • The University of Texas Health Science Center will establish a regulatory path for testing the efficacy of therapeutics for aging by conducting a Phase III hybrid trial to repurpose three FDA-approved drugs: SGLT2 inhibitor, rapamycin, and semaglutide.
  • Columbia University Mailman School of Public Health will identify biomarkers responsive to interventions that improve aging outcomes in humans by performing combined analysis of multiple, previously performed intervention trials.
  • Apollo Alpha will test whether an orally bioavailable compound that crosses the blood-brain barrier and targets energy homeostasis, lipid metabolism, and inflammation can improve aging outcomes.
  • Cambrian BioPharma is awarded USD 30.8 million to support the development of its next-generation selective mTORC1 inhibitors.
  • Linnaeus Therapeutics will benefit from USD 22 million, according to a separate press release, to explore whether activation of the G protein-coupled estrogen receptor (GPER) with its lead pipeline candidate LNS8801 can impact aging.
  • And the University of Rochester will test the impact on ageing of an already approve compound with established safety profile.