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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
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Spermidine is essential for fasting-mediated autophagy and longevity
Sebastian J Hofer1,2,3,4,5, Ioanna Daskalaki6,7, Martina Bergmann1
1Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Nature Cell Biology
|August 8, 2024
Summary
Caloric restriction and fasting boost longevity by increasing spermidine, a natural compound. This polyamine pathway is crucial for fasting
Area of Science:
- Metabolic pathways and aging research
- Cellular autophagy and longevity mechanisms
Background:
- Caloric restriction (CR) and intermittent fasting (IF) are known to extend lifespan and healthspan.
- Spermidine, a natural polyamine, is associated with autophagy enhancement, geroprotection, and reduced disease incidence.
Purpose of the Study:
- To investigate if the benefits of CR and fasting are dependent on polyamine metabolism.
- To explore the role of spermidine in mediating the physiological effects of fasting.
Main Methods:
- Measured spermidine levels in yeast, flies, mice, and human volunteers under CR or IF.
- Utilized genetic and pharmacological methods to block spermidine synthesis.
- Assessed autophagy, lifespan, healthspan, and disease markers in response to pathway perturbation.
Main Results:
- Spermidine levels increased across species with CR and IF.
- Blocking spermidine synthesis impaired fasting-induced autophagy and abrogated lifespan/healthspan benefits.
- Spermidine's effects were linked to autophagy induction and eIF5A hypusination.
Conclusions:
- The polyamine-hypusination axis is a conserved metabolic hub controlling fasting-mediated autophagy and longevity.
- Spermidine is a critical mediator of the health benefits conferred by fasting and caloric restriction.
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