Dietary Spermidine Improves Cognitive Function

Dietary Spermidine Improves Cognitive Function

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*This is a summary of the findings from a recent study titled "Dietary Spermidine Improves Cognitive Function." Further information and details on this study are located in the links below.*

Aging has fascinated patients and doctors alike for centuries, and the study of how and why we age remains on the forefront of health research. The pathophysiologies associated with aging, like neurodegenerative disorders and overall cognitive decline, lead to increased dependence and decreased lifespan and health span. While decreased cognitive performance is a well-understood indicator of aging, the reasons why this happens and the root causes still remain just out of reach for scientists. The decreased brain function, often shown in disorders associated with the hippocampus have been linked to mitochondrial dysfunction, a key factor in the plasticity and neurotransmission in the central nervous system (CNS). As we age, the mitochondria become bigger, therefore less effective and can be traced back to a lapse in quality control, or mitophagy. The process of autophagy and mitophagy slows as we age, leading to an increase in poorly-functioning mitochondria and reduced oxidative phosphorylation as well as other respiratory complexes. A potential treatment that slows the process of aging would go far in battling these symptoms of age and have great positive effects on overall health.

An article recently published, titled “Dietary Spermidine improves cognitive function” looks at the application of Spermidine to combat the age-related neural decline across several species while also backing the idea that increased mitophagy from dietary intake correlates with cognitive performance in humans. Spermidine, a naturally occurring polyamine, has strong ties to autophagy and mitophagy, but new research has linked dietary intake of spermidine with improved cognitive function in flies, mice and humans.

Spermidine (SPD), a naturally occurring polyamine has been demonstrated to extend life and health span across multiple species in an autophagy-dependent manner. In mice, dietary spermidine induces mitophagy, the selective process of degrading damaged mitochondria to allow for improved abundance and respiration of healthy mitochondria. In flies, dietary intake of spermidine has been shown to preserve synaptic flexibility and reduce memory impairment brought on by age. In aged mice, supplementation of SPD improves cognitive functions and has direct effects molecularly in the hippocampus to enhance respiratory capacity. In humans, increased dietary SPD shows a lower risk for cognitive impairment and decline. A proposed mechanism of spermidine is the hypusination of the eukaryotic translation initiation factor 5A (elF5A), which increases the translation of autophagy regulator TFEB and mitochondrial proteins in T/B lymphocytes. Mice and flies supplemented with dietary SPD showed increased respiration and O2 consumption. These studies are shown to be conserved among tested species and partially independent of age phenotypes as well as coinciding with increased ATP levels after 10 days of feeding.

While dietary intake of the polyamine spermidine shows promise in fighting several facets of cognitive decline associated with the aging process, the research has also shown that the effectiveness of SPD is dependent on the functionality of autophagy and mitophagy within the individual. In the absence of the gene Atg-7, essential for autophagy, spermidine was still able to improve respiration for the heterozygous Atg7+/- gene, but effects were completely lost on the Atg-/- gene. However, it was still shown that SPD supplementation protects from age-induced mitochondrial dysfunction in a dependent manner with the Atg7- and Pink1/park genes. Furthermore, in humans, dietary SPD intake reduced the chances for developing a cognitive impairment in an inverse dose-response relationship. Additionally, a recent study has shown positive correlations between dietary SPD and increased hippocampal volume and cortical thickness in elderly humans. Across all species (flies, mice and humans) the mitochondrial function and cognitive performance show great potential for treating cognitive disorders. During normal aging, dietary spermidine acts as a neuroprotective, which coupled with it’s availability, could act as a strategy to prevent disease-driven and age-related cognitive decline within the population.


Cell Reports. 2021 April 13. doi:10.1016/j.celrep.2021.108985. Dietary spermidine improves cognitive function. Sabrina Schroeder, Sebastian J.Hofer, Andreas Zimmermann, Raimund Pechlaner, et al.