Columbia Gets ARPA-H Funding to Map Biomarkers That Measure How Fast People Are Aging

Life expectancy has climbed steadily in wealthy countries for over a century. The number of years those additional decades are spent in good health has not kept pace. Americans are living longer and spending more of that extended life managing chronic diseases - diabetes, cardiovascular disease, cognitive decline - that accumulate with age. The healthcare system is built to treat those diseases once they appear. What it lacks is a way to measure whether interventions are slowing the aging process itself, before diseases emerge.

That measurement problem is the focus of a new five-year project at Columbia University Mailman School of Public Health, funded through the Advanced Research Projects Agency for Health (ARPA-H) as part of the PROactive Solutions for Prolonging Resilience (PROSPR) program. The project, called FAST - which integrates clinical and biological data from multiple trials - is led by Daniel Belsky, PhD, associate professor of Epidemiology at Columbia and affiliated with the Robert N. Butler Columbia Aging Center.

The Core Problem FAST Is Solving

Clinical trials for aging-related interventions face a fundamental difficulty: aging itself is slow. A trial designed to test whether a drug reduces age-related disease must follow participants for years or decades before enough endpoints accumulate to draw conclusions. That timeline makes trials prohibitively expensive and slow.

The solution FAST pursues is biomarkers - measurable biological signals that change earlier and more reliably in response to aging-slowing interventions than clinical outcomes like disease or death. If a drug slows aging, there should be detectable molecular changes in blood or tissue within months, not years. Identifying those early signals would allow researchers to confirm much faster whether an intervention is working.

Rather than launching new trials, FAST will analyze data and biological samples from completed clinical trials. The project has already incorporated trials involving four of five priority drug classes identified by the research team: metformin, SGLT-2 inhibitors, GLP-1 agonists, and rapamycin. These drugs were originally approved for specific conditions - type 2 diabetes, cardiovascular disease - but have shown broader benefits across multiple diseases in both human studies and animal models. Preliminary results from the FAST initiative suggest rapamycin may slow ovarian aging by approximately 20 percent, potentially extending fertility by up to five years. Other trials show improvements in cardiovascular biomarkers, patient-reported health status, and reduced progression to diabetes.

Why These Drugs

Metformin, SGLT-2 inhibitors, GLP-1 agonists, and rapamycin all target biological pathways associated with aging - not just disease management. Rapamycin acts on the mTOR pathway, which regulates cell growth and metabolism and has been consistently linked to lifespan extension across species from yeast to mice. Metformin activates AMPK, an energy sensor that also influences aging pathways. GLP-1 agonists and SGLT-2 inhibitors, while newer additions to the list, have both demonstrated protection against multiple age-related conditions beyond the indications for which they were first approved.

"Current treatments focus on managing diseases after they emerge," Belsky said. "Our goal is to identify measurable biological signals that show when interventions are slowing the aging process itself - so we can preserve health, independence, and quality of life as people grow older."

How the FAST Project Works

The project brings together experts from five institutions spanning aging biology, clinical trials, proteomics, metabolomics, epigenetics, biostatistics, and computational biology. Belsky serves as principal investigator, with co-leadership from Nir Barzilai, MD, of Albert Einstein College of Medicine, and Mahdi Moqri, PhD, of Brigham and Women's Hospital. Zohn Rosen of Columbia Mailman School will serve as project manager.

All data generated by FAST will be made available to qualified researchers through the Columbia Data Platform (CDP), a secure cloud-based infrastructure operated by Redivis on Google Cloud. The open-access approach reflects the project's goal of accelerating the field rather than keeping discoveries proprietary.

"PROSPR was designed to allow the first clinical trials for aging to be possible," said Andrew Brack, ARPA-H Program Manager and creator of the PROSPR program. "To make clinical trials shorter than aging itself, we need biomarkers that change early in response to health-promoting interventions, which is why the FAST project is so important."

What Success Would Look Like

If the FAST project identifies reliable early biomarkers of aging deceleration, the downstream implications extend well beyond academic research. Drug developers testing new compounds in early-phase trials could use these biomarkers to see within months whether their drug is affecting the aging process - dramatically reducing the time and cost of development. Clinicians could eventually use the same measures to track individual patients' biological age and adjust interventions accordingly.

"Older adults will soon visit clinics, learn their biological age, receive targeted interventions, and see themselves getting younger within months," said Barzilai. The ambition is significant; the timeline remains to be demonstrated. Finding biomarkers that reliably capture aging deceleration across different interventions, populations, and tissues is technically demanding - and the field has seen previous candidates that did not replicate well across studies.

The FAST project's approach of mining multiple completed trials simultaneously, rather than running one new trial, is designed to accelerate discovery while managing cost. Whether the biomarkers that emerge hold up across broader populations and different drug combinations will be the next test.