Ultimate Longevity Bible

Pathway

Polyamine Metabolism

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

ObservationalStrong animal data, supportive human cohorts

What it is

Polyamines (putrescine, spermidine, spermine) are small organic polycations present in every cell. They bind nucleic acids, modulate translation, support DNA-damage repair, and regulate ion channels. They are made endogenously, obtained from diet, and produced by gut bacteria.

The biosynthetic pathway: ornithine → (ODC) → putrescine → spermidine → spermine. ODC is highly regulated and is a classic target of cancer biology (DFMO inhibits it).

Why it matters in aging

  • Tissue polyamine levels decline with age in most studied tissues.
  • Spermidine induces autophagy by inhibiting EP300 acetyltransferase, permitting autophagy-gene de-acetylation and activation.
  • Lifespan extension in yeast, worms, flies, and mice from dietary spermidine supplementation.
  • Human cohort data (Bruneck, others) link higher dietary spermidine intake to lower cardiovascular and all-cause mortality.

Dietary sources

Wheat germ, soy, mature cheese, mushrooms, legumes, amaranth, natto. A polyamine-rich diet delivers 5–25 mg/day; supplementation can add 1–6 mg/day.

Cancer caveat

ODC and polyamine synthesis are upregulated in many cancers (neuroblastoma, melanoma). DFMO — an ODC inhibitor — is approved for neuroblastoma maintenance. The "more polyamines = better" framing of supplementation is context-dependent; growing tumours may not be the place to add fuel.

Related entries

Spermidine, Disabled macroautophagy, Autophagy machinery.

References

  • Madeo, F., Eisenberg, T., Pietrocola, F. & Kroemer, G. Spermidine in health and disease. Science 359, eaan2788 (2018).

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