LongevityAnti-Aging

Spermidine

Spermidine

Overview

Spermidine is a naturally occurring polyamine found in all living cells and in many foods including wheat germ, soybeans, aged cheese, and mushrooms. It is one of the most potent known inducers of autophagy — the cellular self-cleaning process that removes damaged proteins and organelles — and has demonstrated lifespan extension in multiple model organisms including yeast, flies, worms, and mice. Human observational data from the ESTHER cohort study linked higher dietary spermidine intake to reduced all-cause mortality and cardiovascular mortality, spurring clinical trials in cardiac and cognitive aging applications.

Where does Spermidine sit?

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Mechanism of Action

Spermidine's primary longevity mechanism is robust induction of autophagy through inhibition of EP300, an acetyltransferase that normally suppresses autophagy-initiating proteins. By inhibiting EP300, spermidine releases the brake on autophagy induction, allowing cells to efficiently clear damaged proteins, dysfunctional organelles, and other cellular debris that accumulates with aging. Enhanced autophagy has downstream effects on inflammation reduction, mitochondrial quality control, proteostasis maintenance, and cellular rejuvenation. Spermidine also modulates the hypusination of eIF5A — a translation factor required for the synthesis of proteins involved in autophagy and immune function. Its cardiovascular benefits in animal models appear mediated through improved cardiac autophagy, reduced fibrosis, and enhanced mitochondrial function in cardiomyocytes.

Dosage Information

Typical Dose

1-6 mg daily

Frequency

Once daily

Administration

Oral capsule or dietary intake

Notes

Wheat germ is the richest dietary source. Supplement forms typically use wheat germ extract. Human clinical trials have used doses of 1.2 mg daily with beneficial cardiovascular outcomes.

Potential Side Effects

Very well-tolerated in clinical trialsMild GI discomfort (rare)No significant adverse effects reported at studied doses

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Quick Facts

Administration
Oral capsule or dietary intake
Typical Dose
1-6 mg daily
Frequency
Once daily
References
0 curated + 0 from PubMed