title: Spermidine-triggered autophagy ameliorates memory during aging.
abstract: The aging process drives the progressive deterioration of an organism and is thus subject to a complex interplay of regulatory and executing mechanisms. Our understanding of this process eventually aims at the delay and/or prevention of age-related pathologies, among them the age-dependent decrease in cognitive performance (e.g., learning and memory). Using the fruit fly Drosophila melanogaster, which combines a generally high mechanistic conservation with an efficient experimental access regarding aging and memory studies, we have recently unveiled a protective function of polyamines (including spermidine) against age-induced memory impairment (AMI). The flies' age-dependent decline of aversive olfactory memory, an established model for AMI, can be rescued by both pharmacological treatment with spermidine and genetic modulation that increases endogenous polyamine levels. Notably, we find that this effect strictly depends on autophagy, which is remarkable in light of the fact that autophagy is considered a key regulator of aging in other contexts. Given that polyamines in general and spermidine in particular are endogenous metabolites, our findings place them as candidate target substances for AMI treatment.
authors.affiliation: Department of Genetics, Institute for Biology; Freie Universität Berlin; Berlin, Germany; NeuroCure Cluster of Excellence; Charité Berlin; Berlin, Germany.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.affiliation: Institute for Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.affiliation: Department of Genetics, Institute for Biology; Freie Universität Berlin; Berlin, Germany.
authors.forename: Varun K
authors.initials: VK
authors.lastname: Gupta
authors.affiliation: Department of Genetics, Institute for Biology; Freie Universität Berlin; Berlin, Germany.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bhukel
authors.affiliation: Department of Genetics, Institute for Biology; Freie Universität Berlin; Berlin, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Mertel
authors.affiliation: Institute for Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Eisenberg
authors.affiliation: Institute for Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000502:physiology*; D008568:Memory / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D013095:Spermidine
keywords: Drosophila melanogaster; autophagy; brain; dementia; spermidine