Spermidine is gaining more popularity as a supplement to slow down aging. 

Spermidine is an interesting anti-aging compound, with various scientific studies supporting its potential for longevity (R,R,R). 

Our bodies naturally produce spermidine, which is mainly known for its ability to induce autophagy, a very important process to keep our cells healthy and young. 

Spermidine also has other effects on longevity, like reducing inflammation (R), but scientists believe that one of the main effects of spermidine is its ability to increase autophagy (R,R).

However, research studies have also found that spermidine likely does not get absorbed into the human body, so there is reason to be concerned about its efficacy from oral supplementation (R).

Spermidine and Autophagy 

Autophagy means “self-digestion”; it’s the process by which cells break down their waste materials (such as proteins) and old or damaged cellular components, such as mitochondria (the power plants in our cells). 

One of the reasons why we age is a decline in autophagy: cells start to accumulate more waste material and become less able to break down their old or damaged components. 

This accumulation of cellular waste and cell components hinders the functioning of the cell, which leads to many aging-related problems. 

Spermidine within the body can increase autophagy (R). That way, cells can clear up their waste materials and damaged components, leading to younger, healthier cells. 

Besides spermidine, there are various other substances that can also increase autophagy and even increase lifespan (see further down below). 

Why Spermidine Is Not Enough

Taking spermidine for “anti-aging” is not ideal, as studies, including one conducted in April 2023, have found that it is not orally absorbed ( “High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study” R). 

Additionally, aging is caused by many processes besides a decline in autophagy, the main mechanism of action of spermidine. 

So simply improving autophagy is not enough to substantially slow down aging. 

After all, we also age because of many other processes, such as epigenetic changes, crosslinking, DNA damage, the rise of senescent cells, mitochondrial damage, inflammation (“inflammaging”), and various other processes (as explained here) – causes that even the spermidine that your body produces does not address.

Therefore, it’s important to take multiple anti-aging or longevity substances, instead of only one like spermidine. 

That’s why we created NOVOS Core, which contains 12 of the most science-based substances to slow down aging, acting on at least 12 causes of aging. 

Nonetheless, increasing autophagy is still important to slow down aging. 

Below, we listed various substances that can increase autophagy and that have been shown to extend lifespan. 

These substances can also impact other aging mechanisms beyond just autophagy. 

Alternatives to Spermidine for Inducing Autophagy (and Beyond)  

1. Lithium 

Lithium is a mineral found everywhere in nature. It can also induce autophagy (R,R). 

Contrary to spermidine, many more studies done both in humans and other species demonstrate that low-dose lithium can slow down aging and extend lifespan (R,R,R,R,R,R,R,R). 

Learn more about the anti-aging effects of lithium here. 

2. Glucosamine

Glucosamine is a substance that occurs naturally in our body. It’s an important component of cartilage and skin and of the extracellular matrix, which glues together all our cells. 

Glucosamine is one of the very few supplements found to be associated with longer lifespans and less heart disease in humans (R,R,R). 

One way glucosamine achieves this is by inducing autophagy (R,R,R). It can also reduce inflammation and increase the production of mitochondria, which are the power plants of our cells. 

Learn more about the longevity effects of glucosamine here.

3. Acetyl-glucosamine in hyaluronic acid

Acetyl-glucosamine is a naturally occurring substance. It’s one of the building blocks of hyaluronic acid, which gives plumpness to our skin and which is also an important component of supportive tissue everywhere in our body. 

Acetyl-glucosamine has been shown to extend lifespan (R). It does this by inducing the “unfolded protein response” (UPR), which is a response of cells against damage caused by too much accumulation of proteins in the body. 

The UPR leads to increased autophagy and increased production of chaperones, which are small molecules or proteins that protect proteins against damage and sticking together so they don’t pile up in the cells.  

We wrote more about the longevity effects of acetyl-glucosamine and hyaluronic acid here.

4. Fisetin 

Fisetin is mostly known as a senolytic, meaning it can kill off senescent cells, which is a good thing given senescent cells accumulate everywhere in our bodies, which contributes to aging. 

However, fisetin has many other beneficial effects in the body.

For example, like spermidine, it can induce autophagy (R,R,R). Fisetin can also reduce the accumulation of proteins that play a role in Alzheimer’s disease (R,R,R). 

You can learn more about fisetin and longevity here.

5. Pterostilbene

Pterostilbene is a naturally occurring molecule (found in blueberries, for example) that has been shown to have various beneficial effects. 

Pterostilbene is a better absorbed and longer active alternative to resveratrol, a widely known and popular anti-aging substance. 

Studies have shown that pterostilbene can also induce autophagy (R,R). 

6. Glycine 

Glycine does not really stimulate autophagy. However, it works as a chaperone, which means it gently sticks to proteins and protects proteins against damage and clumping. 

That way, less autophagy is needed to clean up these damaged or clumped-together proteins. 

However, glycine has various other interesting longevity effects, as we explain here.

Spermidine and Longevity 

Spermidine is a promising molecule to slow down aging. However, it will likely mainly impact a small part of the aging process, such as autophagy. 

As we highlighted above, various other substances can also induce autophagy, like glucosamine, micro-dosed lithium, and fisetin. 

However, given aging is caused by so many different processes, it’s important to address as many of these processes as possible with other substances. 

Therefore, we recommend taking a longevity “multivitamin,” like NOVOS Core, containing various science-based substances that act on different aging mechanisms in a synergistic way.