The REPROGRAM trial will test whether three-week interventions with metformin (1500mg), fisetin (100mg), or spermidine (15mg) can reduce senescent cell burden and reverse key aging mechanisms in 60 healthy adults over 70. The study measures senescence-associated β-galactosidase in adipose tissue as the primary endpoint, alongside comprehensive assessment of aging hallmarks including autophagy dysfunction, immunosenescence, chronic inflammation, and epigenetic aging. This represents the first randomized controlled trial systematically comparing these three leading geroprotectors head-to-head in healthy older adults using direct tissue analysis rather than blood biomarkers alone. The approach addresses a critical gap in aging research, where most geroprotector studies focus on diseased populations or rely on indirect measures. While the three-week timeframe may seem brief for detecting meaningful biological changes, previous research suggests senolytic compounds like fisetin can rapidly clear senescent cells. However, the study's short duration and small sample size may limit detection of clinically meaningful effects. As this is a preprint protocol awaiting peer review, the methodology and endpoints may undergo revision. If successful, this trial could establish standardized approaches for testing anti-aging interventions and provide crucial mechanistic insights into how these compounds affect human aging biology.