Spermidine: a catalyst for autophagy and longevity

Spermidine: a catalyst for autophagy and longevity

Spermidine is a naturally occurring polyamine (organic compounds that have more than two animo groups), which has the ability to stimulate cytoprotective autophagy. It has gained popularity over the past decade for its proposed longevity effects which not only includes autophagy promotion, but also, supports cellular growth and renewal, cardiovascular health, neuroprotection, and has anti-inflammatory and antioxidant properties. Here, we will take look at what spermidine is, what it does, and where to get it in a bit more detail.


Spermidine Synthesis, Structure, And Function

While spermidine is found in certain foods, and can be supplemented, it is naturally produced in our bodies. The biosynthesis of this compound in humans involves a well-defined metabolic pathway that starts with the amino acid ornithine. Ornithine in the case of spermidine synthesis is decarboxylated, meaning it loses a carboxyl group, which in turn creates putrescine. Putrescine then undergoes a series of enzymatic reactions where aminopropyl groups (derived from the decarboxylation of S-adenosylmethionine [SAMe] to decarbonylated SAMe) are added. The addition of these aminopropyl groups then forms spermidine. Because of its structure, spermidine is highly reactive and able to interact with various biological molecules, like nucleic acids and proteins. An example of why this is significant is shown by how spermidine is able to bind to DNA and RNA, which in return helps to stabilize these molecules. Stable ribonucleic acids are essential for various processes including DNA replication, transcription (the process by which RNA is made from DNA), and translation (the process by which proteins are synthesized from RNA).

Because spermidine interacts with proteins, it is able to influence their structure and function. This modulation is crucial for protein activation, ensuring enzymes are functioning properly, and the regulation of metabolic pathways. Spermidine’s impact on proteins also influences cellular growth, differentiation, and survival. The structural properties of spermidine underpin its roles in cell growth, proliferation, and autophagy, while modulating cell stress responses. These are all functions that are vital for maintaining cellular health, protecting against various diseases, and thus increasing longevity.

Spermidine has several effects that make this compound deserving of more attention. In terms of what it can do, spermidine is able to promote autophagy, encourage cellular growth and renewal, is cardioprotective, neuroprotective, and has anti-inflammatory and antioxidant effects, thus positively impacting longevity. Lets break this down a bit.



Autophagy is our bodies way of cleaning itself on the cellular level. During this process, damaged cellular components, like organelles and proteins, are degraded and recycled to maintain cell health. Enhanced autophagy is linked to improved cellular function, disease resistance, and longevity. Essentially, when our body is able to do proper maintenance on itself, including the smallest pieces of us (like our cells and organelles), we are able to live healthier, longer lives.

In this case, spermidine is able to induce autophagy in multiple organs, including liver, heart, and muscles. The way spermidine seems to be doing this is by adjusting the expression levels of autophagy related genes (Atg) such as Atg 7, Atg 11, and Atg 11. These specific genes were up regulated in aging yeast, mice, worms, flies, and cultured mammalian cells upon supplementation. Spermidine also regulates autophagy by inducing the expression of transcription factor elF5A, which increases the synthesis of transcription factor, TFEB, which positively regulates the expression of autophagy. Spermidine induces autophagy a third way by inhibiting protein acetylation, which has the potential to induce or inhibit autophagy.


Cellular Growth And Renewal

Cell growth and renewal is the physiological process which involves the between cell proliferation (an increase in cell numbers), differentiation (unspecialized cells becoming specialized), and death.

As we said above, spermidine is involved in the synthesis of nucleic acids and proteins which are essential for cell growth and division. It also stabilizes RNA and DNA structures, which in turn supports the genetic integrity and function of cells. The significance of this is probably understandable, but essentially our tissues must undergo continuous repair and development, and spermidine help ensure this occurs more effectively at the level of the cell.


Cardiovascular Health

When it comes to cardiovascular health and spermidine, there may be a few things happening. While there are mostly only mice studies out there for this, spermidine seems to improve cardiovascular health by improving endothelial function (the inner lining of blood vessels in this case), reducing blood pressure by inducing nitric oxide (NO) production, improving lipid metabolism, sequestering reactive oxygen species (ROS), thus potentially lowering heart disease risk.



In the context of neuroprotection and spermidine, we are once again met with that word we keep saying. Autophagy! By promoting autophagy, spermidine is able to aid in the removal of toxic protein aggregates that are hallmarks of diseases like Alzheimer’s and Parkinson’s. Autophagy in this case can delay the onset or progression of both of these conditions, while interfering with this process will contribute to promoting these conditions.

There is also some evidence suggesting that spermidine may improve cognitive function and memory, which is likely due to its roles in performing cellular maintenance and by protecting against cellular damage.


Where Can I Get More Spermidine?

Spermidine can be found in several foods such as soybeans, cheese, mushrooms, whole grains, grapefruit, oranges, peas, rice/rice bran, mangos, chick peas, broccoli, cauliflower, and corn. One food stan stands out to me personally when I think of spermidine, is our favorite, smelly, fermented soybean dish, Natto! Sure, the texture is… interesting, and the smell is a bit off putting, but this might just be the most rich sources of spermidine you can find. Spermidine can also be found in supplement form, which can make ensuring you get this into your diet even easier!

In conclusion, spermidine emerges as a compelling polyamine with multifaceted roles in enhancing cellular health and promoting longevity. This naturally occurring compound, synthesized in our bodies and available in various foods, stands out for its ability to stimulate cytoprotective autophagy, support cellular growth and renewal, offer cardioprotection, provide neuroprotection, and exhibit anti-inflammatory and antioxidant properties. Its interaction with biological molecules, such as nucleic acids and proteins, underscores its significance in stabilizing these essential components, thereby facilitating crucial processes like DNA replication, transcription, and translation. Moreover, spermidine's influence on protein structure and function further highlights its importance in cell proliferation, differentiation, and survival. The breadth of research discussed herein points to spermidine's potential in not only advancing our understanding of cellular mechanisms but also in opening new avenues for promoting health and longevity. Whether through diet—where foods like soybeans, cheese, mushrooms, whole grains, and notably natto stand out as rich sources—or supplements, increasing spermidine intake could be a key strategy in enhancing quality of life and extending healthy years, thereby warranting further attention and research into its benefits.

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