No Clinically Validated Biomarker of Biological Age for Use as an FDA Trial Endpoint

We lack a reliable, FDA-accepted way to measure biological age. Without this, testing anti-aging interventions requires decades-long trials waiting for disease or death. Epigenetic clocks like GrimAge and DunedinPACE show promise but disagree with each other and have not been validated as regulatory endpoints.

Epigenetic clocks (Horvath, GrimAge, PhenoAge, DunedinPACE) measure DNA methylation patterns correlated with aging but produce inconsistent results across interventions. The CALERIE trial showed significant reduction in DunedinPACE and PhenoAge from caloric restriction but no effect on GrimAge or Horvath clocks — despite all being second-generation clocks. Proteomic clocks, metabolomic panels, and composite indices add dimensions but lack concordance. No clock has been validated as a surrogate endpoint in a prospective RCT with hard clinical endpoints.

Why It Matters

Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and diabetes — diseases causing ~70% of all deaths globally. The ARPA-H PROSPR program is investing $34.5M at Stanford specifically to develop an FDA-grade Intrinsic Capacity score. Without a validated biomarker, longevity trials require thousands of participants for 5-10+ years.

Startup Approach

Build a multi-omic biological age platform combining epigenetic, proteomic, metabolomic, and functional data into a composite score. Validate against longitudinal outcomes in UK Biobank and All of Us. Seek FDA Breakthrough Device designation for use as a clinical trial endpoint. Partner with pharma running longevity trials.

NIH Funding

NIA budget ~$4.5B (FY2025). ARPA-H PROSPR allocated $34.5M to Stanford for Intrinsic Capacity score and $52M to Buck Institute for chronic disease prediction. NIA Geroscience Network prioritizes aging biomarkers.

Who's Working On It

Steve Horvath (Altos Labs), Morgan Levine (Altos Labs), Daniel Belsky (Columbia, DunedinPACE), Stanford PROSPR team ($34.5M ARPA-H), Buck Institute ($52M ARPA-H), Elysium Health (Index), TruDiagnostic, Tally Health