title: Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
abstract: Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the condition. Polyamines are among the substances found to decrease with age in the human brain. We found that levels of polyamines (spermidine, putrescine) decreased in aging fruit flies, concomitant with declining memory abilities. Simple spermidine feeding not only restored juvenile polyamine levels, but also suppressed age-induced memory impairment. Ornithine decarboxylase-1, the rate-limiting enzyme for de novo polyamine synthesis, also protected olfactory memories in aged flies when expressed specifically in Kenyon cells, which are crucial for olfactory memory formation. Spermidine-fed flies showed enhanced autophagy (a form of cellular self-digestion), and genetic deficits in the autophagic machinery prevented spermidine-mediated rescue of memory impairments. Our findings indicate that autophagy is critical for suppression of memory impairments by spermidine and that polyamines, which are endogenously present, are candidates for pharmacological intervention.
authors.affiliation: 1] Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany. [2] NeuroCure, Charité, Berlin, Germany.
authors.forename: Varun K
authors.initials: VK
authors.lastname: Gupta
authors.forename: Lisa
authors.initials: L
authors.lastname: Scheunemann
authors.forename: Tobias
authors.initials: T
authors.lastname: Eisenberg
authors.forename: Sara
authors.initials: S
authors.lastname: Mertel
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bhukel
authors.forename: Tom S
authors.initials: TS
authors.lastname: Koemans
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Kramer
authors.forename: Karen S Y
authors.initials: KS
authors.lastname: Liu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schroeder
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.forename: Christoph
authors.initials: C
authors.lastname: Magnes
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.forename: Shubham
authors.initials: S
authors.lastname: Dipt
authors.forename: André
authors.initials: A
authors.lastname: Fiala
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.forename: Martin
authors.initials: M
authors.lastname: Schwaerzel
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D004330:Drosophila; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D011073:Polyamines; D013095:Spermidine