spermidine

# Spermidine: An Autophagy-Inducing Polyamine for Eye Health **Spermidine** is a naturally occurring polyamine found in all cells and in many aging-friendly foods. It has recently attracted attention as an **autophagy inducer** and “longevity” nutrient. Autophagy is a cellular “cleanup” process that degrades damaged proteins and organelles (including mitochondria) to maintain cell health. In model organisms, spermidine robustly extends lifespan, likely by reactivating autophagy ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4326581/#:~:text=autophagosomes%20and%20lysosomes%20,spermidine%20also%20reduced%20the%20overall)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5806691/#:~:text=Aging%20is%20associated%20with%20an,provide%20cardioprotection%20in%20mice%20that)). In cultured cells and animals, spermidine **suppresses the histone acetyltransferase EP300**, lowering protein acetylation and thereby accelerating autophagic flux ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4326581/#:~:text=autophagosomes%20and%20lysosomes%20,spermidine%20also%20reduced%20the%20overall)). At the same time, spermidine has a large safety margin; to date *“no adverse effects of exogenous supply of spermidine have been reported”* ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC4326581/#:~:text=all%20cells%2C%20including%20those%20of,retards%20the%20manifestation%20of%20several)), and dosing studies in humans (~1–3 mg/day) have increased intake by only ~10–20% over diet without toxicity ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5807086/#:~:text=bodyweight%20or%202,safety%20limit%20for%20the%20treatment)). ## Autophagy and Mitochondrial Quality Control By inducing autophagy, spermidine helps cells clear damaged components and maintain mitochondrial health. For example, chronic spermidine feeding in aged mice **enhanced cardiac autophagy and mitophagy**, improved mitochondrial respiration, and reduced markers of cellular aging ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5806691/#:~:text=Aging%20is%20associated%20with%20an,provide%20cardioprotection%20in%20mice%20that)). These cardioprotective effects required intact autophagy machinery: mice lacking the autophagy gene Atg5 in heart cells did *not* benefit from spermidine ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC5806691/#:~:text=coinciding%20with%20increased%20titin%20phosphorylation,cardiac%20hypertrophy%20and%20a%20decline)). Improved mitochondrial quality is also seen in neurons: spermidine restored bioenergetics in aged human neurons and in animal models by boosting mitochondrial respiration and ATP production ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC11673406/#:~:text=enhanced%20mitochondrial%20respiration%20in%20both,MMP%20in%20young%20neurons%20were)). Such mitophagy-promoting effects are relevant to long-lived neurons (like retinal ganglion

Spermidine and Autophagy: A Longevity Nutrient for the Aging Eye

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