1. Unique Anti-Aging Benefits of Spermidine
One of the most intriguing nutritional factors in the realm of anti-aging is a unique polyamine called spermidine. As its name suggests, spermidine was first discovered in human semen by the renowned Dutch scientist Antonie van Leeuwenhoek, often referred to as the "Father of Microbiology," in 1678. While spermidine is crucial for sperm function, it also plays a significant role in cells throughout the body.
Source: Wikipedia
Spermidine combats the aging process through various biological mechanisms. Its role as an enhancer of autophagy (see our previous paragraph about” Autophagy”) and mitochondrial function (the energy-producing compartments of cells) is key to the notable anti-aging effects discussed in this article.
The practical application of these effects involves using a spermidine-rich diet or spermidine supplementation as an anti-aging strategy.
In aging models and animal studies, spermidine has been shown to extend lifespan whether administered throughout life or later in life. For humans, maintaining spermidine levels throughout the lifespan may contribute to longevity. Blood levels of spermidine and its metabolite spermidine are lower in people aged 60 to 80 compared to those under 50. Interestingly, individuals over 90 have spermidine levels like those under 50, suggesting a correlation between higher spermidine levels and longer life.
2. Functions of Spermidine
1. Supporting Cellular Function
Spermidine plays a crucial role in cell function and survival by activating key molecules involved in:
- Cell growth
- DNA stability
- Transcription of genetic information
- Protein synthesis
- Enhancing immune health
- Spermidine also significantly impacts immune responses and antioxidant systems, especially in protecting membrane lipids and DNA.
2. Activating Metabolism
Moreover, spermidine activates a major metabolic switch, an enzyme called AMP-activated protein kinase (AMPk). AMPk activity is vital for energy metabolism and is also linked to longevity. As we age, cellular AMPk activity decreases, leading to insulin resistance, liver damage, abdominal (visceral) fat accumulation, and muscle mass loss (sarcopenia). The activation of AMPk may be a key anti-aging effect of spermidine.
3. Longevity Benefits of Spermidine
Enhanced autophagy has been observed in exceptionally healthy centenarians, which seems to be a key goal for living healthier, longer lives. Genetics play a significant role in autophagy, but the expression of autophagy genes can be significantly influenced by diet, lifestyle, and dietary supplements. Spermidine is emerging as a key dietary factor in enhancing autophagy.
Image by Philipp Steichen
Spermidine enhances autophagy by acting on multiple autophagy-promoting genes, including the autophagy gene ATG5. People who overexpress this gene may live longer. The expression of ATG5 is reduced by oxidative and free radical damage and decreased mitochondrial function. Thus, spermidine appears to counteract these factors' inhibitory effects on autophagy.
Besides experimental evidence suggesting that spermidine intake can extend lifespan, human studies also indicate that higher spermidine intake is associated with lower overall mortality. Spermidine also shows promise in preventing aging, particularly in the brain, heart, liver, joints, and muscles, which are especially susceptible to the adverse effects of aging. By enhancing autophagy, spermidine can combat aging in these and other tissues.
Impaired autophagy increases oxidative damage, accelerating aging. It also leads to uncontrolled cellular protein construction, reduced cellular energy production by inhibiting mitochondrial function, and other biochemical challenges associated with faster cellular aging. These effects impact every tissue in the body, particularly the brain, the most metabolically active tissue. Age-related declines in autophagy also contribute to sarcopenia, the gradual loss of muscle mass and strength associated with aging.
Preventing the formation and accumulation of cellular debris is key to helping your body manage it. Chronic, low-grade inflammation is a hallmark of accelerated aging in humans. This process, known as inflammation, also leads to reduced autophagy.
Inflammation has several triggers, such as poor blood sugar control and a lack of key anti-inflammatory dietary factors like omega-3 fatty acids, polyphenol-rich foods like berries, other fruits, leafy greens, and carotenoid-rich vegetables.
Inflammation reduces mitochondrial function, primarily due to damage and stress caused by free radicals and pro-oxidants. This leads to more cellular debris formation within cells. Therefore, the term "garb-aging" is also used to describe the effects of excessive cellular debris accumulation, reduced autophagy, or both. Spermidine may help prevent garb-aging by acting as an antioxidant and enhancing autophagy.
4. Food Sources of Spermidine
Spermidine is present in many foods, albeit in small amounts. The highest concentrations are found in wheat germ, whole grains, legumes, soy products, and mushrooms. Aged cheese and fermented foods, as well as chicken liver or beef liver, are also good sources.
Source: healthbiocare
The estimated daily spermidine intake for adults in the United States and Europe is about 12.5 mg per day. Three tablespoons of wheat germ provide about 5 mg of spermidine, approximately 40% of typical daily intake.
In addition to dietary intake, spermidine is also formed within the body. One pathway involves the amino acid ornithine and its metabolite putrescine. This pathway involves converting putrescine to spermidine via the enzyme spermidine synthase. Spermidine can be converted to spermine and back to spermidine. While spermidine, spermine, and putrescine can interconvert, spermidine is the predominant and most important polyamine in human cellular physiology.
Gut bacteria can also produce spermidine and other polyamines. Since not all gut bacteria produce polyamines, different microbiome compositions can lead to more favorable spermidine production. In the intestinal wall, spermidine has numerous beneficial effects, including extending cell lifespan, restoring damaged intestinal epithelium, and improving cellular energy.
5. Benefits of Spermidine Supplements
Supplementing with spermidine is a viable way to increase spermidine intake. Interestingly, when healthy volunteers consumed 15 mg of spermidine daily, plasma levels of spermine significantly increased without affecting spermidine or putrescine levels. Spermine is transported to body tissues via the bloodstream, where much of it is converted back to spermidine. Spermine also has some benefits.
In addition to extensive experimental and human research indicating that higher spermidine intake can prevent age-related cognitive decline, several clinical trials on wheat germ extract concentrated in spermine have shown positive effects in elderly patients with memory and cognitive function decline.
A recent double-blind study focused on the effects of spermidine intake among 85 subjects aged 60 to 96 from six nursing homes. One group received grain rolls (Roll A), each providing 3.3 mg of spermidine. The second group received rolls baked with wheat bran instead of wheat germ (Roll B), each providing 1.9 mg of spermidine. In addition to memory tests, blood samples were collected to measure spermidine levels. Results indicated a clear link between spermidine intake, blood spermidine levels, and improvements in cognitive ability and memory. Based on the results and blood measurements, the minimum daily dose of spermidine required for improvement was calculated to be 3.3 mg (about two tablespoons of wheat germ). This determination proved very important.
Another double-blind, randomized, placebo-controlled trial indicated that spermidine supplements containing 1.2 mg of spermidine daily for three months could prevent memory loss in elderly subjects. These encouraging results led to a 12-month randomized controlled trial called the SmartAge trial, aimed at determining the effects of spermidine supplementation on brain function and related biomarkers in long-term cognitive decline patients. However, the daily spermidine dose in this study was only 0.9 mg, and no statistically significant improvements were found in the SmartAge trial. As mentioned earlier, the threshold dose for spermidine to produce positive effects is estimated to be 3.3 mg daily. Therefore, the dose was insufficient to yield noticeable benefits.
Another study on spermidine intake is crucial for discussing brain health. This study examined the spermidine intake and adherence to a Mediterranean diet in elderly subjects with cognitive decline. The study used magnetic resonance imaging (MRI) to measure brain structure. Typically, as many people age, key structural changes in the brain, such as total brain volume, hippocampal volume, and cortical thickness, are lost.
Higher spermidine intake was positively correlated with improvements in all these structural measurements. It enhanced the benefits of the Mediterranean diet in maintaining brain health during aging.
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