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Spermidine’s Link to the Hallmarks of Aging

One of the powerful effects of the  hallmarks of aging as a framework for understanding aging, is that it changed the way researchers and scientists are approaching the search for solutions.  The focus on interventions that can stop or even reverse the 9 hallmarks of decline has led to the popularization of NAD supplementation as a healthspan extension strategy that is reasonably --but not incontrovertibly- backed by science.  This framework is also surfacing Spermine, a  polyamine (organic compound with more than two amino groups) that isfound in living tissues.  Research to date points to the possibility that spermidine canimpact 7 of the 9 processes of cellular decline. 

So what exactly is spermidine? What are the mechanisms by which it is deemed to be beneficial for healthy aging? What evidence is there to support its purported effects on longevity?  And where can you find it?   

This is what we learned:

What Is Spermidine?

Spermidine is an organic compound found in human tissues. Originally discovered in spermatozoa (hence its name) this compound has been implicated as having metabolic functions in human cells like maintaining cell membrane potential, controlling intracellular pH, and regulating the enzyme neuronal nitric oxide synthase (nNOS) in the brain. As a possible longevity component, the role of spermidine is not entirely understood, but preliminary studies suggest a role in autophagy; the compound has also been suggested to play a role in reducing systemic inflammation, lipid metabolism, regulating cell growth, reducing oxidative stress, mitochondrial respiration, and cardiac aging.

Where Can I Find Sources of Spermidine?

Spermidine can be synthesized by the body from ornithine, a metabolite of the urea cycle, or by the gut microbiome. It can also be consumed through foods like wheat germ, soybeans, cheese, nuts and broccoli to name a few.

Spermidine in Health and Disease

Source: Spermidine in Health and Disease

While a growing number of studies suggest that spermidine plays a role in cellular processes that are key to longevity, levels of spermidine in the cells tend to decrease with advancing age. This is likely due to a breakdown in the efficiency of cell machinery as a result of DNA damage, mitochondrial dysfunction, and decreased nutrient sensing. This leaves food as a potential source, but the amount of the compound found in foods is relatively low—and likely too low to be the primary source of spermidine in your longevity protocol. As a result, there’s a growing interest in taking spermidine as a supplement, something we encountered in our research.

One of the major players in the game is a company based in Austria called Longevity Labs. Their scientific advisory board includes one of our favorite longevity gurus, David Sinclair, as well as Frank Madeo, one of the first researchers to suggest that spermidine may be age-protective. The company recently launched a supplement in the US called SpermidineLIFE ($99 or $89/month with subscription). The supplement is made from GMO-free wheat germ and according to the company, nearly 4.5 pounds of raw wheat is needed to produce one capsule. Admittedly, the product isn’t cheap, but offers a good alternative for anyone who would rather use a supplement than try to increase intakes of spermidine through food.

Can Spermidine Really Help Me Live Longer?

Studies in both animal and human models suggest that spermidine supplementation may help extend the lifespan. For example, in yeast spermidine triggers histone deacetylation to help maintain the integrity of DNA and reduce oxidative stress. Causally, the effects of spermidine have been attributed to its ability to induce autophagy, a process that’s critical to preventing the proliferation of DNA damage we accumulate through exposure to free radicals and oxidative stress. According to this article from Rhonda Patrick, autophagy is split into two main categories:

  • Non-selective autophagy (basal autophagy)—part of normal “housekeeping” within the cell or a response to stressors that disrupt homeostasis (e.g, starvation)
  • Selective autophagy—targets specific organelles, pathogens, and/or protein aggregates in the cell for destruction in order to improve cell function

There are three primary triggers (starvation, calorie-restriction, exercise) for autophagy in the cells, each of which occurs in response to a decrease in the concentration of acetyl CoA (the end product of glycolysis). The decrease in substrates needed to produce energy prompts homeostatic mechanisms (e.g., breakdown of organelles to release additional nutrients) to kick in order to preserve the cell. 

Spermidine in Health and Disease

Source: Spermidine in Health and Disease

Accordingly, research has shown that some compounds (e.g., resveratrol, rapamycin, spermidine) act as calorie-restriction mimetics and are able to induce autophagy in the cells without the requisite reduction in calories. Essentially, spermidine tricks your cells into thinking you're restricting your intake even if your diet remains unchanged.

Go Deeper: Check out this short clip from Rhonda Patrick to learn more about how spermidine induces autophagy in the cells and what that means for our lifespans.

Aside from autophagy, spermidine has also been shown to impact gene expression, cell growth and proliferation, leading scientists to classify it as a geroprotector. More recent studies have explored the role spermidine plays in other processes that may help extend the life of the cells such as reducing inflammation and regulating cell growth. 

One of the areas where scientists have seen these specific effects is in cardiovascular health. In animal models, spermidine supplementation triggered anti-inflammatory processes that lowered blood pressure and induced cardiac autophagy. Combined together, spermidine appears to be cardioprotective at least in rats. In humans, nutrient data taken from food questionnaires suggests that individuals who consume spermidine-rich foods had a lower incidence of cardiovascular diseases and had lower blood pressure than individuals who did not. While human trials don’t point to causality, the association is compelling enough to warrant further study.

Spermidine has also shown neuroprotective effects in fruit flies and roundworms. This study suggests that supplementing spermidine alleviates neurodegenerative processes that occur Parkinson's disease.

Spermidine supplementation presents an exciting, new pathway to possibly extending our healthspans. The majority of studies to date have been performed in animals, though because spermidine is a naturally occurring compound that we consume and synthesize, it is likely safe to include as part of your longevity protocol. Consult your doctor before you begin supplementing spermidine.

Go Deeper: Check out this recently published review on spermidine to catch up on all the research related to its uses in health and longevity. 

Share your experiences with spermidine with us or anything we may have left out:

This content is general in nature and for informational purposes only. Nowgevity content is not intended to constitute medical or other professional advice and should not be considered a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor or other qualified healthcare provider with any questions you may have regarding a medical condition, procedure, or treatment, whether it is a prescription medication, over-the-counter drug, vitamin, supplement, or herbal alternative. Never disregard professional medical advice or delay in seeking it because of something you have on Nowgevity’s website or emails. Reliance on any information provided herein is solely at your own risk. 

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