What Spermidine Does

Spermidine is a polyamine that turns on autophagy (Greger, 2023, p. 29). I know that sentence is packed with a lot of words. Autophagy is the body’s recycling system. It is a chance for the body to use up its old parts or degrade them. What old parts? Fat stores, but also old protein molecules, DNA and RNA fragments, organelles, glycogen, and intracellular pathogens (Frankel, Lubas, & Lund, 2017; Mizushima & Levine, 2010; Scott, Schuldiner, & Neufeld, 2004; Yang et al., 2024). This is great! It is like your body just got an upgrade. Spermidine stimulates autophagy by upregulating the enzyme AMPK (Liu et al., 2020). By binding onto AMPK, spermidine can phosphorylate (think turn on) the enzyme (Liu et al., 2020) Spermidine also upregulates AMPK by raising the amount of mitochondrial reactive oxygen species (mtROS) which then stimulates AMPK (Liu et al., 2020). Autophagy is turned on by AMPK either by autophagy phosphorylating, autophagy proteins or regulating various genes associated with autophagy (Li & Chen, 2019). Spermidine can also stimulate autophagy independent from AMPK (Greger, 2023, p. 25, 29).

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References:

Greger, M. (2023). How not to age: The scientific approach to getting healthier as you get older. Thorndike Press (a part of Gale, a Cengage Company).

Frankel, L. B., Lubas, M., & Lund, A. H. (2017). Emerging connections between RNA and autophagy. Autophagy, 13(1), 3–23. https://pmc.ncbi.nlm.nih.gov/articles/PMC5240835/Greger, M. (2023). How Not to Age: The Scientific Approach to Getting Healthier as You Get Older. Flatiron Books.

Liu, R., Li, X., Ma, H., Yang, Q., Shang, Q., Song, L., … Shi, Y. (2020). Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy. Free Radical Biology and Medicine, 161, 339–350. https://doi.org/10.1016/j.freeradbiomed.2020.10.029Li, Y., & Chen, Y. (2019). AMPK and autophagy. In Advances in Experimental Medicine and Biology (Vol. 1206, pp. 85–108). Springer. https://pubmed.ncbi.nlm.nih.gov/31776981/

Mizushima, N., & Levine, B. (2010). Autophagy in mammalian development and differentiation. Cell, 143(4), 677–686. https://www.sciencedirect.com/science/article/pii/S0092867411012761