Spermidine in health and disease

Madeo F, Eisenberg T, Pietrocola F, Kroemer G

Published in Science

Abstract

Comprehensive review of spermidine as an autophagy inducer with anti-aging properties. Discusses mechanisms including histone acetylation, cardiovascular protection, neuroprotection, and metabolic benefits.

Methodology

Narrative review in Science synthesising mechanistic, animal-model and epidemiological evidence on spermidine.

Key Findings

Spermidine induces autophagy via inhibition of EP300 and hypusination of eIF5A, extends lifespan in yeast, flies, worms and mice, protects cardiac and neuronal tissue in rodent models, and higher dietary spermidine intake is associated with lower cardiovascular and all-cause mortality in human cohorts.

Conclusions

Spermidine is one of the best-characterised caloric-restriction mimetics, with strong preclinical lifespan and cardioprotection data and supportive but observational human evidence; randomised human outcome trials are still lacking.

Limitations

Review of predominantly animal and epidemiological data; human evidence is observational and confounded by overall diet quality, and optimal supplemental dose in humans is undefined.