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I.R.F. / Aging news / General / 09100801

Novel Players in Aging – Spermidine
Posted on: October 8, 2009

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Scientists report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells.

Skeletal formula of spermidine
Spermidine, skeletal 2D formula
(Public domain image, taken from wikipedia.org, image author - Ben Mills)

Ball-and-stick model of spermidine
Spermidine, ball-and-stick 3D model
(Public domain image, taken from wikipedia.org, image author - Ben Mills)

In addition, spermidine administration potently inhibited oxidative stress in ageing mice.

In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan.

The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, it was found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

Source: Eisenberg T, Knauer H, Schauer A, Buttner 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, Grubeck-Loebenstein B, Herker E, Fahrenkrog B, Frohlich KU, Sinner F, Tavernarakis N, Minois N, Kroemer G, Madeo F.; Induction of autophagy by spermidine promotes longevity.; Nat Cell Biol. 2009 Oct 4.
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