Spermidine Promotes Longevity through the Induction of Autophagy


Spermidine is a polyamine compound that has various metabolic functions within organisms.   It was originally isolated from semen and is found in ribosomes and living tissues.  

Spermidine is synthesized from putrescine, using an aminopropylic group from decarboxylated S-adenosyl-L-methionine (SAM). The reaction is catalyzed by spermidine synthase.

Spermidine has recently emerged as exhibiting anti-aging properties. Its supplementation increases lifespan and resistance to stress, and decreases the occurrence of age-related pathology and loss of locomotor ability. 

The Table below lists the Spermidine content in certain foods:  1

Spermidine Content in Certain Foods

FoodSpermidine mg/kg
Broccoli (cooked)~25
Cauliflower (cooked)~25
Cheddar, 1yr old199.5
chicken liver48.7
Green peas46.6
Rice bran50
Soybean,dried (German)128
Soybean,dried (Japanese)207

The mechanism of spermidine at the molecular level appears to multi-faceted, including:  2

  • autophagy
  • inflammation reduction
  • lipid metabolism
  • regulation of cell growth
  • proliferation and death

Research indicates that the main pathway used by Spermidine to effectuate its benefits is the MAPK pathway.  2   The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell.  The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division.

Researchers conducted a study wherein they administered spermidine and found that it markedly extended the lifespan of yeast, flies and worms, and human immune cells. 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.

The researchers found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.   3  

Ingestion of Spermidine is either accomplished by consuming foods containing Spermidine (See Table above) or through the conversion of Putrescine to Spermidine.  Putrescine is a precursor for the endogenous production of Spermidine. 

S-Adenosylmethionine (SAMe) is an essential cofactor for the conversion of Putrescine to Spermidine. 

Currently, there are no Spermidine supplements for consumer purchase.

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