Intervention
Spermidine
Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
What it is
Spermidine is a natural polyamine present in many foods, with the highest concentrations in wheat germ, soybeans, mature cheese, mushrooms, and amaranth. Endogenous spermidine declines with age in most tissues.
Why it’s of interest
- Induces autophagy across cell types.
- Extends lifespan in yeast, worms, flies, and mice (multiple studies).
- Human cohort data (Bruneck, EPIC) link higher dietary spermidine to lower all-cause and cardiovascular mortality.
- Reduced cardiac aging markers in mouse models.
Mechanism
Spermidine inhibits acetyltransferases (EP300) that suppress autophagy, producing an autophagy-permissive cellular state. It also influences mitochondrial respiration and translation fidelity.
Practical use
- Dietary: wheat-germ supplementation provides ~1–2 mg/day.
- Supplement formulations typically deliver 1–6 mg/day from wheat-germ extract.
- Tolerability is good; no serious safety signals at typical doses over short-term human studies.
Evidence ceiling
Human RCTs in older adults show modest cognitive and inflammation signals. No human lifespan data.
Related entries
Disabled macroautophagy, Autophagy machinery, Mediterranean diet.
References
- Eisenberg, T. et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat. Med. 22, 1428–1438 (2016).