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Review
. 2021 Aug;17(8):2037-2039.
doi: 10.1080/15548627.2021.1933299. Epub 2021 Jun 9.

Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging

Sebastian J Hofer  1   2   3 , YongTian Liang  4 , Andreas Zimmermann  1   2   3 , Sabrina Schroeder  1   2   3 , Jörn Dengjel  5 , Guido Kroemer  6   7   8 , Tobias Eisenberg  1   2   3 , Stephan J Sigrist  4 , Frank Madeo  1   2   3
Affiliations
Free PMC article
Review

Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging

Sebastian J Hofer et al. Autophagy. 2021 Aug.
Free PMC article

Abstract

Spermidine is a natural polyamine, central to cellular homeostasis and growth, that promotes macroautophagy/autophagy. The polyamine pathway is highly conserved from bacteria to mammals and spermidine (prominently found in some kinds of aged cheese, wheat germs, nuts, soybeans, and fermented products thereof, among others) is an intrinsic part of the human diet. Apart from nutrition, spermidine is available to mammalian organisms from intracellular biosynthesis and microbial production in the gut. Importantly, externally supplied spermidine (via drinking water or food) prolongs lifespan, activates autophagy, improves mitochondrial function, and refills polyamine pools that decline during aging in various tissues of model organisms, including mice. In two adjacent studies, we explored how dietary spermidine supplementation enhances eEF5/EIF5A hypusination, cerebral mitochondrial function and cognition in aging Drosophila melanogaster and mice.

Keywords: Autophagy; Drosophila; Pink1; hypusination; learning; memory; mitophagy; polyamines; spermidine.

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Conflict of interest statement

F.M. and S.J.S. have equity interests in The Longevity Labs (TLL), a company founded in 2016 that develops natural food extracts. T.E. has equity interests in and conducts paid consultancies for TLL. G.K. has been holding research contracts with Bayer Healthcare, Daiichi Sankyo, Glaxo Smyth Kline, Genentech, Eleor, Institut Mérieux, Kaleido, Lytix Pharma, PharmaMar, Samsara, Sanofi, Sotio, Vascage and Vasculox/Tioma. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific cofounder of everImmune, Samsara and Therafast Bio. F.M. and T.E. are inventors on a pending patent application related to this work.

Figures

Figure 1.
Figure 1.
Proposed model of dietary spermidine’s effects on hypusination, mitochondria and cognitive function. Elevated dietary spermidine sets off a cascade, leading to increased levels of hypusinated eEF5/EIF5A, which orchestrates a network of effects leading to improved mitochondrial function and consequently enhanced cognitive function during aging. Dashed lines represent likely effects which were not directly measured or observed in our studies [1,2]. ATG3, autophagy related 3; DHS, deoxyhypusine synthase; DOHH, deoxyhypusine hydroxylase; EIF5A, eukaryotic translation initiation factor 5A; TFEB, transcription factor EB; PINK1, PTEN induced kinase 1
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References

    1. Schroeder S, Hofer SJ, Zimmermann A, et al. Dietary spermidine improves cognitive function. Cell Rep. 2021;35(2):108985. - PubMed
    1. Liang Y, Piao C, Beuschel CB, et al. eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction. Cell Rep. 2021;35(2):108941. - PubMed

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Grants and funding

F.M. is grateful to the Austrian Science Fund FWF [SFB LIPOTOX F3007 and F3012, DK-MCD W1226, as well as grants P29203, P29262, P27893, P31727] and the Austrian Federal Ministry of Education, Science and Research, as well as the University of Graz for grants “Unkonventionelle Forschung-InterFast and Fast4Health,” as well as “flysleep” [BMWFW-80.109/0001-WF/V/3b/2015]. We acknowledge the support of the Field of Excellence BioHealth, of NAWI Graz and the BioTechMed-Graz flagship project “EPI- Age.

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