Spermidine: A novel autophagy inducer and longevity elixir

  title={Spermidine: A novel autophagy inducer and longevity elixir},
  author={Frank Madeo and Tobias Eisenberg and Sabrina B{\"u}ttner and Christoph Ruckenstuhl and Guido Kroemer},
  pages={14 - 160 - 162}
Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in… 

Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways

It is established that the protective effects of Spd can be exerted through different pathways that depending on the oxidative stress scenario do or do not involve autophagy.

Spermidine induces autophagy by inhibiting the acetyltransferase EP300

Results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent Autophagy inducers including spermidine de facto act as EP300 inhibitors.

Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers

Essential parts of the apoptotic signaling network were subjected to post-translational modifications during the drug-induced autophagy response, suggesting potential crosstalk and balancing between autophagic and apoptosis.

Epibrassinolide-induced autophagy occurs in an Atg5-independent manner due to endoplasmic stress induction in MEF cells

EBR is an anticancer drug candidate with selective cytotoxicity for cancer cells, in addition the induction of autophagy and PA metabolism are critical for responses of normal cells against EBR.

Spermidine promotes mating and fertilization efficiency in model organisms

It is demonstrated that pheromone-induced shmoo formation requires spermidine, and it is identified as an important mating component in unicellular and multicellular model organisms, supporting an unprecedented evolutionary conservation of the mechanisms governing fertilization-related cellular fusion.

The regulation of autophagy differentially affects Trypanosoma cruzi metacyclogenesis

Both polyamine metabolism and autophagy are key processes during T. cruzi metacyclogenesis that could be exploited as drug targets to avoid the parasite cycle progression.

Spermidine and spermine are enriched in whole blood of nona/centenarians.

Although there is an important correlation between polyamines levels and age groups, further studies are warranted to fully understand the role of polyamines in determining life span, and longitudinal and nutritional studies might suggest potential therapeutic approaches to sustain healthy aging and to increase human life span.

Polyamine depletion inhibits the autophagic response modulating Trypanosoma cruzi infectivity

The data showed that depleting intracellular polyamines by inhibiting the biosynthetic enzyme ornithine decarboxylase with difluoromethylornithine (DFMO) suppressed the induction of autophagy in response to starvation or rapamycin treatment in two cell lines, suggesting DFMO is an FDA-approved drug that may have value in limiting Autophagy and the spread of the infection in Chagas disease and possibly other pathological settings.