| Taurine | A 2023 Science paper reported taurine declines with age and that supplementation extends healthspan in mice and monkeys. Drove enormous uptake, at doses up to 14 g/day | A 2025 Aging Cell paper plus an NIH/NIA follow-up across the Baltimore Longitudinal Study, rhesus monkeys and mice found circulating taurine flat or *rising* with age — the opposite of the founding premise. The original lead author no longer recommends supplementation |
| Spermidine | One of the most elegant mechanisms in the field: eIF5A hypusination, the only protein modification of its kind in human biology, enabling translation of autophagy transcription factors | The flagship human cognition trial (SmartAge, N=100, 12 months) was null on its primary endpoint, and a bioavailability study found 40 mg/day barely moved circulating polyamines — far above what commercial products deliver |
| Time-restricted eating | Framed as working through a circadian mechanism independent of calorie reduction | A rigorous isocaloric trial (Science Translational Medicine) found it shifted BMAL1/CLOCK expression but did not improve cardiometabolic health once calories were matched. The mechanism is real; most of the practical benefit comes from eating less |
| Metformin as a free geroprotective add-on | AMPK activation, mTORC1 inhibition, autophagy induction — mechanistically attractive and cheap | A 2025 JCEM RCT (N=72) found it *blunted* exercise-induced gains in vascular insulin sensitivity and aerobic capacity, by suppressing the same mitohormetic ROS signal that drives PGC-1α. A genuine trade-off, not a theoretical one |
| Rapamycin, in one high-profile protocol | The most reproducible geroprotective molecule in animal work; up to 30% mouse median lifespan extension in some ITP arms | Discontinued after ~5 years on self-reported lipid abnormalities, worsening glucose control, elevated resting heart rate and recurrent infections. Note carefully: the field's leading rapamycin researcher did not follow, and remains more bullish. An n=1 tolerance report is not a verdict on a molecule |
| Unity Biotechnology | The most advanced clinical senolytics programme in existence | Missed its Phase 2b primary endpoint, ran out of cash, laid off all staff and dissolved in 2025. Clinical promise does not reliably convert into commercial survival |
| Cerebrolysin, in the reference protocol | A porcine-brain-derived peptide preparation, run for three months | No measurable effect; discontinued and reported publicly. The scarcest artefact in this entire space, and the behaviour most worth copying from that project |