Hasta la Vista Brain Aging: Astaxanthin Alleviates Pathological Brain Aging by Promoting Nerve Communication

With increasing elderly populations, the aging of the brain has gradually become clearer. Brain aging refers to the aging phenomenon that occurs gradually in brain tissue form, structure, and function, leading to cognitive dysfunctions, such as learning and memory. For these reasons, how to effectively delay cognitive dysfunction caused by brain aging has become a hot topic in related fields. Although the mechanisms of brain aging are complex and made up of many factors, oxidative stress is generally considered to be the leading cause of brain aging. 

Now, Liu and colleagues have shown that an organic reddish pigment with antioxidant qualities found in many types of seafood called astaxanthin improved and enhanced the spatial memory and learning abilities of mice mimicking Alzheimer’s disease. Their article published in Neural Regeneration Research shows that astaxanthin works by increasing the levels of factors that play a role in brain health and synapses — the site of transmission of electric nerve impulses between two nerve cells.

“This study may provide a reliable theoretical basis for the prevention and treatment of brain aging and senile dementia, as well as for the further development and clinical application of astaxanthin,” proposed the authors.

SIRT1 and PGC-1α: Guardians of our nerve galaxies

Recent studies have demonstrated that the protein sirtuin 1, or SIRT1, plays a vital role in nerve development, repair, and protection. SIRT1 actions affect pathways involved in cell viability and aging, neuronal protection, and organ metabolism. This longevity-associated protein can regulate intracellular levels of reactive oxygen species — unstable molecules that contain oxygen and that easily reacts with other molecules in a cell — and protect cells from oxidative stress injury.

PGC-1α, a relatively newly discovered protein in the oxidative stress system, plays an essential role as a factor that regulates gene activation for various programs, such as those for cellular antioxidant enzymes. PGC-1α is a core control factor that regulates the cell’s production of mitochondria — the energy hubs of cells.

SIRT1 and PGC-1α have been shown to interact. For example, SIRT1 can adjust the initiation and sustained response of PGC-1α in the oxidative stress state. Hence, SIRT1 is thought to possess the positive biological effect of stimulating PGC-1α. The action of these proteins together has been shown to play a role in synapse plasticity — the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.

The pink pigment: an antioxidant found in salmon, shrimp, and other seafood

Astaxanthin is a reddish pigment that belongs to a group of chemicals called carotenoids. It occurs naturally in certain algae and causes the pink or red color in salmon, trout, lobster, shrimp, and other seafood. This organic pigment plays a vital role in antioxidative and anti-aging processes and also protects synaptic proteins. Since oxidative stress is currently considered to be the main cause of brain aging and astaxanthin can improve oxidative stress under multiple pathological conditions, Liu and colleagues examined whether astaxanthin might have therapeutic effects on brain aging.

Astaxanthin does its best Terminator impression against Alzheimer’s

So, the research team took a mouse model of brain aging mimicking Alzheimer’s disease and tested how astaxanthin affected the performance of these mice in a battery of cognitive tests. For instance, they utilized the Morris water maze — a widely used test in behavioral neuroscience to study spatial learning and memory in which rodents are repeatedly placed in different parts of a pool and use spatial clues to swim through opaque water to find a hidden, sunken platform. Using the Morris water maze, Liu and colleagues saw that astaxanthin greatly reduced the time it took for these mice to find the platform. This suggests that astaxanthin treatment improved and enhanced the spatial memory and learning abilities of these mice.

On the levels of cells and molecules, SIRT1 and PGC-1α were reduced in the hippocampus — the brain area linked to learning and memory — of Alzheimer’s disease mice. Astaxanthin restored the expression of SIRT1 and PGC-1α in these rodents. This finding indicates that the SIRT1/PGC1α signaling pathway may be related to the activation of genes encoding synaptic-related proteins and the spatial memory, learning, and cognitive capacities of mice. 

Astaxanthin treatment also increased the levels of two other proteins important to brain health called brain-derived neurotrophic factor (BDNF) and synaptophysin in the hippocampus. BDNF is an important protein for central nervous system development and neuronal survival, differentiation, growth, and development that can prevent nerve damage and death, improve the pathological state of neurons, and promote the regeneration of damaged neurons. Synaptophysin reflects the number, distribution, and density of synapses as well as also reflects the efficiency of synaptic transmission. Furthermore, BDNF and synaptophysin are also markers of synaptic plasticity as they are involved in the formation and reconstruction of synapses.

Can astaxanthin pump your brain up against aging?

Although how the brain ages remains a conundrum, the results of the present study demonstrate that astaxanthin acts through the SIRT1/PGC-1 signaling pathway to regulate the expression of synaptophysin and BDNF. These findings show that through the SIRT1/PGC-1α signaling pathway, astaxanthin can protect synaptic proteins, increase the expression of synaptophysin and BDNF proteins, and improve learning, memory, and cognitive abilities.

“We will continue to investigate whether astaxanthin upregulates the expression of other synaptic proteins through the SIRT1/PGC-1 signaling pathway, and explore relevant trials to select the appropriate dose of astaxanthin for clinical applications,” concluded the authors.

Furthermore, these findings support testing astaxanthin as a potential therapeutic against brain aging and Alzheimer’s disease in humans. More experimentation is necessary to see if astaxanthin can be to brain aging as Arnold Schwarzenegger’s Terminator is to John Connor — a protector of humanity.

References:

Liu N, Zeng L, Zhang YM, Pan W, Lai H. Astaxanthin alleviates pathological brain aging through the upregulation of hippocampal synaptic proteins. Neural Regen Res. 2021;16(6):1062-1067. doi:10.4103/1673-5374.300460