Tier 3 — preclinical

Spermidine is essential for fasting-mediated autophagy and longevity

Sebastian J Hofer et al.

Nature Cell Biology 2024 26(9):1571-1584

Bibliography

PubMed: PMID 39117797
PubMed Central: PMC11392816
DOI: 10.1038/s41556-024-01468-x
Funding: Supported by Austrian Science Fund grants, Austrian federal and University of Graz programs, Austrian Research Promotion Agency grants, BioTechMed-Graz projects, Agence Nationale de la Recherche and additional disclosed academic funding.
Competing interests: Several authors disclosed commercial relationships. Frank Madeo and Tobias Eisenberg have equity/advisory interests in The Longevity Labs; Frank Madeo and others also disclosed autophagy/fasting-related company interests and consultancies. Full disclosures are listed in the Nature Cell Biology article.

Study snapshot

Design	Multi-species mechanistic study with human fasting observations
Model	Yeast, nematodes, flies, mice, human cells and fasting human volunteers
Sample	Multiple yeast, nematode, fly, mouse, human-cell and human fasting cohorts
Intervention	Fasting/caloric restriction with genetic or pharmacological polyamine-pathway manipulation; spermidine rescue in model systems
Duration	Acute and longer fasting/caloric-restriction protocols plus model-organism healthspan/lifespan experiments; varies by system
Endpoints	Endogenous spermidine; Autophagic flux; eIF5A hypusination; Fasting adaptation; Healthspan and lifespan in model organisms; Human fasting polyamine response

What the study showed, in plain terms

This Nature Cell Biology study showed that fasting raises endogenous spermidine across species, including humans, and that the spermidine-eIF5A-autophagy pathway is required for many fasting benefits in experimental models.

Key findings

The paper strengthens spermidine's role as a conserved metabolic mediator of fasting and autophagy. Human volunteers demonstrated fasting-associated polyamine changes, not that oral spermidine supplements reproduce fasting or extend human lifespan.

What this study can and cannot tell us

Causal longevity and healthspan experiments were performed in model organisms. Human data were physiological fasting observations and cell work rather than randomized oral supplementation outcomes.

Editorial review

Reviewed by the Biohack Blueprint research team

Khaled Mahmoud