Prioritizing Geroscience Interventions for Human Translation: A Multi-Criteria Decision Analysis of 30 Candidates

<title>Abstract</title> <p>Targeting fundamental mechanisms of aging could delay multiple chronic diseases simultaneously, but prioritizing among dozens of heterogeneous candidate interventions lacks a standardized evaluative framework. This study develops a multi-criteria decision analysis (MCDA) to quantitatively compare 30 geroscience interventions spanning repurposed drugs, nutraceuticals, regenerative strategies, and frontier modalities. Each intervention was scored across six prespecified translational domains (preclinical lifespan, healthspan(definition), mechanistic conservation, human trial evidence, safety, accessibility) using predefined rubrics and aggregated with a weighted-sum model. Robustness was validated by Monte Carlo simulation (10,000 iterations) and sensitivity analysis under three stakeholder weighting schemes. The baseline ranking identified a stable top tier led by spermidine (3.7, 95% CI 3.44-3.93), mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (3.6), and SGLT2 inhibitors (3.6). Sensitivity analysis revealed scenario-dependent leadership: metformin ranked first under regulator- and patient-focused weights, while stem cell therapy rose to third under investor-focused weights. No intervention occupied the high-readiness/high-impact quadrant, quantifying a persistent translational gap. An open-access interactive web tool accompanies the framework to support real-time exploration of ranking sensitivity.</p>