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Longevity Briefs: Can Spermidine Prevent Cognitive Decline?

Posted on 10 November 2023

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem: As we grow older, our brain function tends to decline, affecting our memory, learning, and cognition. This is partly due to the accumulated damage to our mitochondria, the tiny power plants within our cells that produce ATP, the cell’s universal fuel. Damaged mitochondria are removed and recycled by a process called autophagy (literally ‘self-eating’), though this process is also called mitophagy when referring to the recycling of mitochondria specifically. Unfortunately, autophagy becomes less efficient with age. This means that an increasing proportion of each cell’s mitochondria become dysfunctional. This not only leads to a decline in available ATP, but also disrupts signalling within the cell and leads to oxidative stress and inflammation.

The discovery: Researchers found that a natural compound called spermidine, which is found in many foods such as cheese, mushrooms, soybeans and nuts, can improve cognitive function in aged mice and humans by boosting autophagy and mitochondrial quality. Spermidine is a type of polyamine, a molecule that is involved in various cellular processes, including protein synthesis and gene regulation. 

The researchers fed aged mice with spermidine for 6 months and found that it increased the levels of a protein called eIF5A, which is essential for autophagy and mitochondrial function. Spermidine also improved the mice’s performance in spatial learning and memory tasks, as well as their behaviour in homecage environment tasks. 

Moreover, the researchers analysed data from a large population-based study in Italy, involving 815 participants aged 45-84, who were followed for 5 years. They found that higher dietary spermidine intake was associated with lower risk of cognitive impairment and decline, as well as better scores in memory and executive functioning tests.

Tables showing the probability of cognitive impairment (left), performance in different cognitive tests (middle), and distribution of cognitive impairment scores (right) according the spermidine intake. Participants were divided into thirds (tertiles) according to spermidine intake. Probability is relative to the lowest intake group.
Dietary spermidine improves cognitive function

The implications: This study suggests that spermidine, a natural compound that is present in our diet, can enhance autophagy and mitochondrial function in the brain, and perhaps improve cognitive performance and protect against age-related decline. The human data examined in this study only showed correlation and not causation. Since this study was published, a clinical trial of spermidine supplementation for subjective cognitive decline was conducted, but failed to find any significant benefits on cognition. However, spermidine remains relatively unstudied in humans and it is still too early to draw conclusions about its health applications. There are many reasons why early clinical trials fail, including insufficient dosage (researchers will rightfully err on the side of caution), or failing to target the correct groups (spermidine might prevent cognitive decline but not reverse it).

Given that spermidine is a safe and accessible compound that can be easily incorporated into our daily nutrition, further research seems warranted. It may be worth consuming foods that are rich in spermidine such as cheese, mushrooms, soybeans and nuts, as well as fruits and vegetables, which can also increase the production of spermidine in our body.

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    Dietary spermidine improves cognitive function

    Title image by Robina Weermeijer, Upslash

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