Spermidine

Spermidine is a naturally occurring polyamine found in all domains of life. It is a positively charged molecule at physiological pH and participates in a variety of cellular processes by interacting with nucleic acids, membranes, and proteins. Spermidine is produced endogenously in cells and is also obtained through the diet.

Biosynthesis begins with ornithine decarboxylase converting ornithine to putrescine. Spermidine synthase then transfers an aminopropyl group from decarboxylated S-adenosylmethionine to putrescine, forming spermidine. The donor molecule, decarboxylated S-adenosylmethionine, is generated by S-adenosylmethionine decarboxylase.

Biological roles of spermidine include stabilization of DNA and RNA structures, modulation of protein function, and support of cell growth and differentiation. A prominent area of interest is its ability to induce autophagy, partly through inhibition of the EP300 acetyltransferase, which affects the acetylation of autophagy-related proteins.

Spermidine is found throughout the body and is produced endogenously, with dietary intake contributing to tissue levels. Dietary sources rich in spermidine include aged cheese, mushrooms, soy products, legumes, whole grains, and certain vegetables.

In health and aging research, spermidine has been linked to autophagy induction and lifespan extension in several model organisms. In humans, observational studies have associated higher dietary spermidine intake with lower risks of cardiovascular disease and mortality, but causality has not been established. Some small clinical trials have reported improvements in cardiovascular markers, yet evidence for lifespan extension remains inconclusive. Safety appears favorable at typical dietary levels, but the broader health implications of high polyamine intake are still being studied.