Spermidine, a physiological autophagy inducer.
Spermidine is a natural polyamine that can stimulate cytoprotective autophagy.
The intracellular concentration of spermidine declines during human aging. Therefore, external supplementation of spermidine can extend life and health span.
A connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested.
Recent epidemiological data supports this notion, showing that an increased uptake of this polyamine diminishes overall mortality associated with cardiovascular diseases and cancer .
Synthesis of the possible mechanisms of action of spermidine.
Autophagy is the main recycling mechanism of the cell, allowing the destruction and re-use of unneeded or damaged molecules or whole organelles. A deficient autophagy has been linked to many age-related diseases .
It has been shown that spermidine can quickly induce autophagy .
Spermidine affects the acetylation profile of many proteins, a significant proportion of them belonging to the human autophagy protein network . The authors reported that spermidine can induce short-term autophagy without transcription of new proteins and that autophagy by spermidine can be regulated by cytoplasmic (de)acetylations.
Although very important for the effects of spermidine on aging, autophagy is not the only mechanism of action involved, as for instance spermidine still increases hydrogen peroxide resistance.
Spermidine can delay aging in humans
Spermidine may counteract the general clock of aging, by a global effect on cellular fitness (A), or may exert specific effects on multiple organ systems engaged in for example cardiovascular function, anticancer immune surveillance or neurodegeneration and thereby reducing the incidence of the major age-related diseases (B).
Future research must elucidate the molecular pathways on which spermidine acts to identify actionable targets that may be used for the treatment and prevention of age-related diseases .
Possible mechanisms of spermidine-mediated rejuvenation.
Aging has been characterized by a chronic inflammation profile that leads to chronic damage to cells and is associated with many age-associated diseases.
Polyamines trigger the production of anti-inflammatory cytokines while decreasing the production of pro-inflammatory ones, but at the same time, polyamine metabolism generates cytotoxic products (such as hydrogen peroxide) that can themselves cause inflammation. Polyamines have mostly anti-inflammatory effects, some of them recently reviewed .
Spermidine also indirectly modulates inflammation via changes induced in lipid composition.
A dysfunction in lipid metabolism can trigger deleterious consequences on health and ultimately aging and lifespan.
Recently, spermidine has been shown to alter lipid metabolism. The changes in lipids profile will modulate membrane fluidity and proneness to oxidative damage as well as signalling.
Spermidine: a longevity elixir.
"SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals"
Published on 21st June in nature communications.
Polyamine supplementation and autophagy induction modulate cellular metabolism and limit SARS-CoV-2 growth in primary human lung cells and intestinal organoids .
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1) Madeo, F., Bauer, M. A., Carmona-Gutierrez, D., & Kroemer, G. (2019). Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?. Autophagy, 15(1), 165–168. https://doi.org/10.1080/15548627.2018.1530929.
2)Minois N. (2014). Molecular basis of the 'anti-aging' effect of spermidine and other natural polyamines - a mini-review. Gerontology, 60(4), 319–326. https://doi.org/10.1159/000356748.
3)Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., Fussi, H., Deszcz, L., Hartl, R., Schraml, E., Criollo, A., Megalou, E., Weiskopf, D., Laun, P., Heeren, G., Breitenbach, M., … Madeo, F. (2009). Induction of autophagy by spermidine promotes longevity. Nature cell biology, 11(11), 1305–1314. https://doi.org/10.1038/ncb1975.
4) Morselli, E., Mariño, G., Bennetzen, M. V., Eisenberg, T., Megalou, E., Schroeder, S., Cabrera, S., Bénit, P., Rustin, P., Criollo, A., Kepp, O., Galluzzi, L., Shen, S., Malik, S. A., Maiuri, M. C., Horio, Y., López-Otín, C., Andersen, J. S., Tavernarakis, N., Madeo, F., … Kroemer, G. (2011). Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. The Journal of cell biology, 192(4), 615–629. https://doi.org/10.1083/jcb.201008167.
5)Minois, N., Carmona-Gutierrez, D., Bauer, M. A., Rockenfeller, P., Eisenberg, T., Brandhorst, S., Sigrist, S. J., Kroemer, G., & Madeo, F. (2012). Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways. Cell death & disease, 3(10), e401. https://doi.org/10.1038/cddis.2012.139.
6)Madeo, F., Carmona-Gutierrez, D., Kepp, O., & Kroemer, G. (2018). Spermidine delays aging in humans. Aging, 10(8), 2209–2211. https://doi.org/10.18632/aging.101517
7)Bjelaković, G., Stojanović, I., Jevtović Stoimenov, T., Pavlović, D., Kocić, G., Rossi, S., Tabolacci, C., Nikolić, J., Sokolović, D., & Bjelakovic, L. j. (2010). Metabolic correlations of glucocorticoids and polyamines in inflammation and apoptosis. Amino acids, 39(1), 29–43. https://doi.org/10.1007/s00726-010-0489-3.
8) Gassen, N.C., Papies, J., Bajaj, T. et al. SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals. Nat Commun 12, 3818 (2021). https://doi.org/10.1038/s41467-021-24007-w