A Tectonic Shift in Aging Research

On February 24, 2026, ARPA-H announced the seven performer teams for its PROSPR program — the most ambitious federal initiative ever designed to treat aging itself, not just age-related diseases. Despite 90%+ of adults over 65 managing chronic conditions, no FDA-approved therapeutics target the biology of aging directly. PROSPR aims to change that by identifying early biomarkers, developing novel clinical trial designs measurable in 1–3 years instead of decades, and testing both repurposed and novel compounds in human participants.

"PROSPR represents a tectonic shift in how we study healthy aging. 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."

— Alicia Jackson, Ph.D., ARPA-H Director
90%
Adults 65+ with ≥1 chronic condition
80%
Adults 65+ with ≥2 conditions
1–3 yr
Trial duration vs decades
726+
Planned participants (VITAL-H alone)
Program Architecture

PROSPR integrates three parallel tracks — biomarker discovery, therapeutic testing, and clinical infrastructure — into a unified framework designed to create a new "healthspan industry."

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Track 1: Biomarker Discovery

Identify physiological and biochemical markers responsive to aging interventions. Columbia FAST project + Stanford PROSPR-IC score development. Surrogate endpoints for 1–3 year trials.

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Track 2: Therapeutic Testing

4 biotech teams testing novel and repurposed compounds: next-gen rapalog (Cambrian), GPER agonist (Linnaeus), retrotransposon inhibitor (Brown/Rochester), stealth BBB compound (Apollo Alpha).

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Track 3: Clinical Infrastructure

UT San Antonio VITAL-H hybrid/decentralized Phase 3 trial. WHOOP wearables + in-home assessment. Regulatory pathway for intrinsic capacity as FDA-grade endpoint.

"I built PROSPR because I kept seeing the same story play out: brilliant scientists uncover exciting ways to target the biology of aging in animal models, only to have those ideas sit on the shelf because there's no clear path to test them in humans. I wanted to change that."

— Andrew Brack, Ph.D., ARPA-H PROSPR Program Manager
Funding Distribution by Team
Known allocations ($ millions, up to)
Team Type Distribution
Academic institutions vs biotech companies
The 7 Performer Teams

Each team received milestone-contingent contracts (not grants) with varying funding amounts. Click any team to expand its profile.

Drug Arena

Comparing all therapeutic compounds being tested across PROSPR, from next-gen rapalogs to repurposed HIV drugs.

Compound Team Class Target Route Key Advantage Stage
Novel Rapalog Cambrian mTOR Inhibitor Selective mTORC1 Oral, daily Next-gen selectivity; avoids mTORC2 side effects Phase 1/2
LNS8801 Linnaeus GPER Agonist G protein-coupled estrogen receptor Oral, once-daily 100+ cancer pts safety data; cardiometabolic signals Phase 1 (oncology) → aging
Censavudine (TPN-101) Brown / Rochester RT Inhibitor LINE-1 reverse transcriptase Oral Decades of HIV drug safety; targets "dark genome" Preclinical → RCT
Stealth Compound Apollo Alpha Metabolic Energy homeostasis / lipid / inflammation Oral, BBB-crossing Brain-penetrant; multi-system metabolic Undisclosed
Rapamycin UT San Antonio mTOR Inhibitor mTORC1 (low-dose) Oral FDA-approved; most studied aging drug; ITP lifespan data Phase 3 (VITAL-H)
Dapagliflozin UT San Antonio SGLT2 Inhibitor Sodium-glucose cotransporter 2 Oral FDA-approved; CV + metabolic benefits proven Phase 3 (VITAL-H)
Semaglutide UT San Antonio GLP-1 Agonist GLP-1 receptor Oral or injection FDA-approved; weight loss + CV + diabetes; massive safety dataset Phase 3 (VITAL-H)
Drug Class Distribution
Therapeutic classes represented across PROSPR
Safety Profile Maturity
Relative human safety data available per compound
Novel vs Repurposed Strategy

PROSPR strategically blends novel compounds (Cambrian's rapalog, Apollo's stealth agent) with repurposed FDA-approved drugs (rapamycin, dapagliflozin, semaglutide, censavudine). The repurposed drugs offer an accelerated path — decades of safety data allow focus on efficacy endpoints. Novel compounds push the frontier of what's targetable. Linnaeus' LNS8801 sits between: originally developed for oncology, now repurposed for aging. This dual strategy maximizes the odds of identifying at least one validated healthspan therapeutic within the 5-year window.

Biomarker Innovation

The core challenge PROSPR solves: aging takes decades, but clinical trials can't wait that long. These teams are building the surrogate endpoints that compress decades of aging into 1–3 year measurable signals.

IC
Intrinsic Capacity (WHO)
5
IC Domains
20 yr
Predictive Horizon
<$100
Target Home Test Cost
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PROSPR-IC Score (Stanford THRIVE)
$34.5M — Led by Dr. Michael Snyder. Harmonizes existing longitudinal health datasets to create a composite healthspan score integrating wearable data (WHOOP), health surveys, functional assessments, and blood biomarkers. Partners: Buck Institute, Methuselah Foundation, YMCA, OpenCures. Goal: FDA-grade surrogate endpoint predicting mortality, hospitalization, multimorbidity, and functional decline up to 20 years ahead. In-home assessment under $100.
Wearable Data Longitudinal FDA-Grade
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FAST Project (Columbia)
Led by Dr. Daniel Belsky (Columbia Mailman) with Dr. Nir Barzilai (Einstein) and Dr. Mahdi Moqri (BWH). Rather than launching new trials, FAST retroactively analyzes biospecimens from completed clinical trials of 4 drug classes: metformin, SGLT2i, GLP-1 agonists, and rapamycin. Partners: OLink (proteomics), TruDiagnostic (epigenetics), Duke, NovoNordisk. All data shared via Columbia Data Platform.
Proteomics Epigenetics Metabolomics
The 5 Domains of Intrinsic Capacity (WHO Framework)

Assessed across all PROSPR intervention trials — the composite that the FDA may recognize as a regulatory-grade endpoint.

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Locomotor
Mobility & physical function
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Cognition
Memory, processing, executive
Vitality
Energy, metabolism, resilience
👁️
Sensory
Vision & hearing acuity
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Psychological
Mood, motivation, wellbeing
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PROSPR-IC Score
Composite of all 5 domains
Biomarker Modality Coverage
Types of biological measurements across PROSPR projects

"Older adults will soon visit clinics, learn their biological age, receive targeted interventions, and see themselves getting younger within months."

— Nir Barzilai, M.D., Albert Einstein College of Medicine (FAST co-PI)
Revolutionary Trial Design

PROSPR's most radical innovation isn't the drugs — it's the clinical infrastructure. Decentralized trials, wearable-driven endpoints, and in-home data collection that could reshape how we test aging therapeutics forever.

VITAL-H Trial (UT San Antonio)
The Flagship Phase 3 — Largest Geroscience Trial Ever Designed
Enrollment
726 adults in their 60s
Study Arms
4 arms: Rapamycin / Dapagliflozin / Semaglutide / Placebo
Design
Hybrid decentralized; in-home + multi-site
Monitoring
Health-tracking ring (activity, heart, sleep) + daily pill
Primary Endpoint
Intrinsic Capacity composite score
Enrollment Start
2027 (planned)
The Paradigm Shift: Traditional vs PROSPR
Traditional Aging Trials
  • Wait for disease/disability to manifest
  • 10–20+ year follow-up needed
  • Disease-specific endpoints (e.g., cancer incidence)
  • Centralized clinical sites only
  • Annual or semi-annual check-ups
  • High cost, slow accrual, massive dropout
PROSPR Design
  • Detect earliest biomarker changes before disease
  • 1–3 year surrogate endpoints
  • Intrinsic Capacity composite (5 domains)
  • Decentralized: in-home + multi-site hybrid
  • Continuous wearable monitoring (WHOOP, rings)
  • Lower burden, broader access, faster readouts
Trial Data Flow
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In-Home
Wearable ring + daily pill + digital surveys
Continuous Monitoring
Activity, sleep, HRV, recovery 24/7
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Multi-Site Visits
Blood draws, cognitive tests, function
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PROSPR-IC Score
Composite healthspan endpoint
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FDA Pathway
Surrogate endpoint validation
Censavudine (Brown/Rochester) Trial Design
Phase 1: Preclinical
Long-term Censavudine in aging mice (Brown + Rochester labs)
Phase 2: Human RCT
200+ adults ages 60–65, 48-week treatment
Clinical Sites
U. Rochester, UConn Health, UT Medical Branch
Endpoints
IC score, biological aging markers, physical performance
Trial Timeline: Key Milestones
Projected PROSPR program milestones across 5-year contract
Aging Pathways Targeted by PROSPR

PROSPR compounds converge on a handful of core aging mechanisms — the "geroscience hypothesis" that a small number of biological drivers underlie most age-related diseases.

AGING Functional Decline · Chronic Disease · Frailty mTOR Signaling mTORC1 → Growth/Autophagy Rapamycin · Cambrian Rapalog GPER Signaling Estrogen receptor → Multi-organ LNS8801 (Linnaeus) Retrotransposons LINE-1 → IFN → Chronic Inflammation "Dark Genome" False Alarm Censavudine / TPN-101 Metabolic Decline Energy · Lipid · Glucose · BBB Homeostatic Dysregulation Apollo Alpha Compound SGLT2 / Renal Glucose reabsorption → CV + Metabolic Dapagliflozin (VITAL-H) GLP-1 Signaling Incretin → Weight + CV + Glucose Semaglutide (VITAL-H) Chronic Inflammation Converging target for 5/7 compounds
Pathway Deep Dives
mTOR The Master Growth Switch

mTORC1 drives cell growth and suppresses autophagy (cellular cleanup). Dysregulated mTOR with age leads to senescent cell accumulation, metabolic decline, and immune dysfunction. Low-dose rapamycin and Cambrian's selective rapalog aim to rebalance mTORC1 without immunosuppressive mTORC2 effects. ITP mouse data: rapamycin extends lifespan 10–25% depending on sex and dose.

LINE-1 The Dark Genome

LINE-1 retrotransposons — virus-like sequences making up ~17% of the human genome — are normally silenced. With age, epigenetic control weakens, LINE-1 becomes active, and the innate immune system detects cytoplasmic DNA as a viral threat, triggering interferon signaling and chronic inflammation. Censavudine blocks the reverse transcriptase that LINE-1 needs to replicate, potentially silencing this false alarm at its source.

GPER From Oncology to Aging

G protein-coupled estrogen receptor (GPER) mediates rapid, non-genomic estrogen signaling across multiple organ systems. Linnaeus' LNS8801 was developed as an oncology drug but showed unexpected cardiometabolic benefits in 100+ cancer patients. The "oncology-to-aging" repurposing is a novel pathway — leveraging an established safety profile to explore broad healthspan effects.

SGLT2 + GLP-1 Metabolic Geroscience

Dapagliflozin (SGLT2i) reduces glucose reabsorption, improving cardiovascular and metabolic outcomes. Semaglutide (GLP-1) promotes weight loss and CV risk reduction. Both are FDA-approved with massive safety datasets. VITAL-H tests them head-to-head against rapamycin and placebo, with aging-specific endpoints — the first time GLP-1/SGLT2i efficacy is measured through a geroscience lens.

Pathway Coverage by Compound
Which aging hallmarks each drug targets (based on known mechanisms)
References

Primary sources, press releases, and scientific literature underlying this tracker.

  1. ARPA-H. "Research teams to add more healthy years to Americans' lives as they age." Feb 24, 2026. arpa-h.gov
  2. ARPA-H. "PROSPR Program Page." arpa-h.gov/explore-funding/programs/prospr
  3. ARPA-H. "ARPA-H launches new program aimed at extending the healthspan of Americans." arpa-h.gov
  4. Longevity Technology. "ARPA-H pours millions into healthspan-focused human trials." Feb 2026. longevity.technology
  5. Longevity Technology. "WHOOP enters $34.5m ARPA-H-backed bid to quantify aging." Mar 2026. longevity.technology
  6. Forbes. "7 Research Teams Awarded $144 Million To Study Age-Related Illnesses." Nietzel, M. Feb 25, 2026. forbes.com
  7. Fight Aging! "A Fair Amount of ARPA-H Funding is Being Used for Clinical Trials Relevant to Aging." Mar 4, 2026. fightaging.org
  8. TIME. "Aging Is Medicine's Biggest Blind Spot." Feb 2026. time.com
  9. Brown University. "With federal award of up to $22 million, researchers to study treatment to slow the human aging process." Feb 24, 2026. brown.edu
  10. UT Health San Antonio. "UT San Antonio to lead $38 million national trial testing drugs to extend healthspan." Mar 2026. uthscsa.edu
  11. Columbia University Mailman School. "ARPA-H Contract to Advance Science of Healthy Aging." Mar 2026. publichealth.columbia.edu
  12. UConn Today. "Aging Research in U.S. Accelerated by Major ARPA-H Contract." Feb 2026. uconn.edu
  13. Bioengineer.org. "URochester Researchers Secure Up to $22M to Investigate a Key Hidden Factor in Aging." Feb 2026. bioengineer.org
  14. AllSci. "US ARPA-H throws USD 144m to tackle aging, universities and biotechs in support." Feb 2026. allsci.com
  15. Labiotech.eu. "11 anti-aging biotech companies leading longevity in 2026." Mar 2026. labiotech.eu
  16. De Cecco, M. et al. "L1 drives IFN in senescent cells and promotes age-associated inflammation." Nature 566, 73–78 (2019). doi:10.1038/s41586-018-0784-9
  17. Beard, J.R. et al. "The World report on ageing and health: a policy framework for healthy ageing." Lancet 387, 2145–2154 (2016). doi:10.1016/S0140-6736(15)00516-4
  18. Belsky, D.W. et al. "DunedinPACE, a DNA methylation biomarker of the pace of aging." eLife 11, e73420 (2022). doi:10.7554/eLife.73420
  19. CDC. "Chronic Disease Among Older Adults." Preventing Chronic Disease (2025). cdc.gov
  20. Harrison, D.E. et al. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice." Nature 460, 392–395 (2009). doi:10.1038/nature08221