Spermidine is essential for fasting-mediated autophagy and longevity.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
08 Aug 2024
08 Aug 2024
Historique:
received:
04
04
2024
accepted:
02
07
2024
medline:
9
8
2024
pubmed:
9
8
2024
entrez:
8
8
2024
Statut:
aheadofprint
Résumé
Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.
Identifiants
pubmed: 39117797
doi: 10.1038/s41556-024-01468-x
pii: 10.1038/s41556-024-01468-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Karl-Franzens-Universität Graz (University of Graz)
ID : Field of Excellence BioHealth
Organisme : Karl-Franzens-Universität Graz (University of Graz)
ID : Field of Excellence BioHealth
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : F3012
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : W1226
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P29203
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P29262
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P27893
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : DOC-50
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P27637-B28
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : I3301-MINOTAUR
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P33957
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : TAI6021000
Organisme : Medizinische Universität Graz (Medical University of Graz)
ID : Flagship project VASC-HEALTH
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SI 849/14-1 (Project-ID 445178831)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SI 849/14-1 (Project-ID 445178831)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 672032
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : FOR2886/2-TP08
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC2167-390884018
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_184781
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_166474/184671
Informations de copyright
© 2024. The Author(s).
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