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Keeping your synapses sharp: How spermidine reverses age-related memory decline

PLOS

Synapses, connecting the neurons in our brains, continuously encode new memories, but the ability to form new memories ("learning") diminishes drastically for many of us as we get older. In the article published September 29 in open-access journal PLOS Biology, work by the groups of Stephan Sigrist from the Freie Universität Berlin, Andrea Fiala (Universität Göttingen) and Frank Madeo (Universität Graz) now shows that specific changes at the level of synapses directly provoke age-related dementia, and that, however, administering a simple substance already found in our bodies, spermidine, can help to avoid such age-related synaptic changes and thereby protect from age-induced memory impairment.

Just like humans, the fruit fly Drosophila melanogaster - a leading model for aging research - suffers from memory impairment with advancing age. The same team of researchers previously observed that Drosophila exhibits an age-induced decline in levels of spermidine, and that these memory deficits can be suppressed by feeding with a diet supplemented by spermidine. They now describe an unexpected scenario that convincingly explains the suppression of memory deficits by spermidine feeding. In a nutshell, synapses within the Drosophila brain seem to narrow their operational space, and thus become increasingly unable to form new memories with age. Dietary supplementation with spermidine, however, prevented these changes. Importantly, when the authors mimicked these age-associated changes by genetic means, learning suffered even in young flies, providing a causal link between generic synaptic mechanisms and age-induced memory impairment. This work promises to open up a new avenue when searching for new therapeutic strategies to fight age-associated dementia, a major health threat of our times.

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In your coverage please use this URL to provide access to the freely available article in PLOS Biology: http://dx.doi.org/10.1371/journal.pbio.1002563

Citation: Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, et al. (2016) Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. PLoS Biol 14(9): e1002563. doi:10.1371/journal.pbio.1002563

Funding: This work was supported by grants from the Bundesministerium für Bildung und Forschung (Smartage, 01GQ1420A) to SJS and CB, the Forschungszentrum für neurodegenerative Erkrankungen to SJS and AE, and the Deutsche Forschungsgemeinschaft to SJS and AB (Exc 257, TP A3 and A6 SFB 958; SFB 740 TP C09). UP and AF were supported by the German Research Foundation (SFB 889/B04) and the German Ministry of Research and Education via the Bernstein Center for Computational Neuroscience Göttingen (grant number 01GQ1005A). FM is grateful to the Austrian Science Fund FWF for grants P23490-B12, P24381, P 27893, I1000 and grant 'SFB Lipotox' and to BMWFW and the Karl-Franzens University for grant 'Unkonventionelle Forschung'. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

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