Original story: ScienceInsider
ARPA-H will “build the train tracks” for first large clinical studies of aging interventions
By: Mitch Leslie
A version of this story appeared in Science, Vol 391, Issue 6790.
(09 MAR 2026) — Aging is the unindicted coconspirator in many of the diseases that can make our later years miserable. But not a single treatment for aging has ever been rigorously tested and approved. By doling out up to $144 million in contracts last month, the Advanced Research Projects Agency for Health (ARPA-H), the U.S. government agency launched in 2022 to sponsor out-of-the-box biomedical science, aims to change that.
The agency’s Proactive Solutions for Prolonging Resilience (PROSPR) program awarded the money to seven teams—four from academia and three from biotechs—to lay the groundwork for phase 3 trials of interventions intended to increase health span, or how long a person can live without developing serious disease. “The vision of PROSPR is to build the train tracks” for these large clinical studies, which are needed to gain the OK from regulators, says Andrew Brack, the ARPA-H manager of the program. “The longevity landscape will look substantially different in 5 years in large part because of the PROSPR program,” he predicts.
PROSPR is “a big step forward because it’s the first serious effort to move our successes with experimental animals into humans,” says biogerontologist Steve Austad of the University of Alabama at Birmingham, who has no connection to the project. “It’s superimportant,” says biologist Morten Scheibye-Knudsen of the University of Copenhagen, who is also not involved in PROSPR. The project “could have a profound effect on population health.”
Drugs, strict diets, and other interventions can stretch—even more than double—the life spans of lab animals and extend how long they remain healthy. But people haven’t benefited from the research. “The problem is how to get a drug approved,” says geriatrician and clinical researcher John Newman of the Buck Institute for Research on Aging, a member of one of the PROSPR teams. “Until you do that, the field is not going to be able to change human health in a big way.”
Showing that a drug actually extends life span would normally require an extremely long follow-up, making a clinical trial impractical. To run trials “that don’t last 20 years,” Brack says, researchers need surrogate biomarkers, measurable aging indicators that don’t require counting years. Scientists have nominated plenty of candidates, including the age-dependent patterns of methyl groups on DNA, walking speed, and even the accumulation of facial wrinkles, as documented in photographs. One goal of ARPA-H’s funding is to validate a biomarker that tracks aging, responds to interventions, and can pass muster with regulators.
What researchers are looking for, Newman says, is “the blood pressure of aging.” The PROSPR team he is part of, which also includes researchers from Stanford University and other institutions, plans to analyze large health data sets, physiological measurements from wrist-worn monitors, and other information to devise such an indicator. They’re hunting for a composite measure, or intrinsic capacity score, that can foretell outcomes such as death, onset of multiple diseases, and hospitalization over the next 20 years. The team also plans to create a home test kit that will allow users to determine their own aging scores.
In contrast, an ARPA-H–backed group that includes geneticist Nir Barzilai of the Albert Einstein College of Medicine as well as colleagues from Columbia University and other institutions hopes to tease an aging indictor out of data from trials of four existing drugs. The drugs, among them the diabetes treatment metformin and the immune suppressant rapamycin, were approved for other conditions but may also affect aging. By combing through data and tissue samples from the trials and from a test of the extreme diet known as calorie restriction, “we will look for biomarkers that changed” and might signal a slowing of aging, Barzilai says.
ARPA-H “did the right thing by focusing on health” instead of extending longevity, Austad says. Improved health is easier to measure, and increasing the health span could provide major social and economic benefits by reducing the medical costs of old age. “And if we live longer, it’s a fine side effect,” Austad says.
PROSPR is also targeting the regulatory pathway. The drug approval process at the U.S. Food and Drug Administration (FDA) and other regulators is typically set up to assess treatments for a specific disease, not a natural process such as aging. In the past, researchers hoping to launch a clinical trial of a potential intervention have been “forced to treat an age-related disease rather than aging itself,” Brack says. For instance, a trial of metformin proposed by Barzilai and colleagues 10 years ago would have measured whether the drug delays the onset of several chronic illnesses such as dementia, cancer, and heart disease. (The trial never started because of a lack of funds.)
Several PROSPR award recipients are planning clinical trials they hope will build confidence in markers of aging. A team led by researchers from the University of Texas Health Science Center at San Antonio, for example, will perform a phase 3 trial of three FDA-approved drugs—rapamycin, a so-called SGLT-2 inhibitor used to treat diabetes, and the weight loss powerhouse semaglutide—in healthy people in their 60s to determine whether the medications inhibit age-related decline in physical and mental functioning. The goal, Brack says, is “to demonstrate a pathway to approval.”
Barzilai says PROSPR shows that the aging field has reached a watershed. “We are at the stage when we can realize the promise” of decades of basic research. But Austad says he wishes the scientists would hurry up. “It’s so exciting I don’t want to wait 5 years.”
doi: 10.1126/science.zjx9oi7