Spermidine

Spermidine is a naturally occurring polyamine compound found in all living organisms. It was first discovered in semen (hence the name) in 1678, but is present in virtually all human cells and tissues. As a polyamine, spermidine plays essential roles in cell growth, proliferation, and differentiation.

The primary mechanism of interest for longevity is spermidine's ability to induce autophagy - the cellular process of cleaning out damaged components and recycling them. Autophagy declines with age, leading to accumulation of cellular damage. Spermidine restores youthful autophagy levels without requiring calorie restriction or fasting.

Epidemiological studies show that people with higher dietary spermidine intake have lower mortality rates, particularly from cardiovascular disease. Animal studies are remarkably consistent - spermidine extends lifespan in yeast, worms, flies, and mice, while improving cardiovascular function, immune response, and cognitive performance.

Human bodies can synthesize spermidine, but production declines with age. Additionally, gut bacteria produce spermidine that can be absorbed. Dietary sources include wheat germ, aged cheese, mushrooms, and fermented foods. Supplementation offers a way to maintain youthful levels despite declining endogenous production.

Unlike many supplements, spermidine has been consumed by humans for millennia through food. Wheat germ and aged cheeses are particularly rich sources. Modern extraction and purification allows for concentrated supplemental forms that would be difficult to obtain through diet alone.

Spermidine's primary mechanism is the induction of autophagy - the lysosomal degradation and recycling of cellular components. This process is essential for maintaining cellular health by removing damaged proteins, dysfunctional mitochondria, and other cellular debris.

Autophagy naturally declines with age, contributing to the accumulation of cellular damage and age-related dysfunction. Spermidine reverses this decline by inhibiting acetyltransferase EP300, which normally suppresses autophagy. This deacetylation activates autophagy-related genes and proteins, including those in the ATG family.

Beyond autophagy, spermidine has several other mechanisms:

1. Mitochondrial protection: Spermidine maintains mitochondrial membrane potential and respiratory function, reducing oxidative stress and cellular energy decline.

2. Anti-inflammatory effects: By clearing damaged mitochondria through autophagy (mitophagy), spermidine reduces inflammasome activation and chronic inflammation.

3. Immunomodulation: Spermidine enhances immune cell function, particularly in older adults, by improving autophagy in immune cells.

4. Cardioprotection: Spermidine improves cardiomyocyte function, enhances cardiac autophagy, and reduces arterial stiffness through effects on endothelial cells.

5. Translation regulation: As a polyamine, spermidine influences protein synthesis and ribosome function, affecting cellular growth and maintenance.

Importantly, spermidine's effects are mediated through the same pathways activated by calorie restriction and exercise, offering potential benefits without lifestyle modifications. The compound is well-tolerated because it is naturally present in the body and food.

Spermidine is found in many foods, with wheat germ, aged cheese, and mushrooms being the richest sources. Dietary intake correlates with longevity in population studies.

No established RDA. Human trials have used 1-10 mg/day. Typical supplemental doses range from 1-3 mg daily. Average dietary intake in Western diets is approximately 10-15 mg/day.

Spermidine extends lifespan in yeast (20%), worms, flies, and mice through autophagy induction. Human epidemiological data shows reduced mortality with higher intake. Direct human longevity trials pending.

Spermidine is available as spermidine trihydrochloride in capsules. Wheat germ extract supplements provide natural food-derived spermidine.