Longevity Articles

Pterostilbene Keeps Aging Cognition Green: The Resveratrol Analog Supports Memory Formation In Older Rats

Pterostilbene Keeps Aging Cognition Green: The Resveratrol Analog Supports Memory Formation In Older Rats

Intake of fruits and other plant-derived foods, particularly berries and nuts, supports healthy cognition while aging. These effects are attributed mainly to the micronutrients that naturally occur in plants called polyphenols, which can support healthy brain-blood circulation and the growth and plasticity of adult brain cells. However, dietary polyphenols have a hard time making it all the way to the brain as the liver and gut metabolize and rapidly excrete them.  

Pterostilbene, an analog of the more famous (and controversial) resveratrol, reaches relatively high levels in the brain tissue after being consumed, where it has been shown to safely support memory formation or maintenance. Research from a group of Italian researchers also shows that pterostilbene supports learning and memory in older rats, underscoring the potential of pterostilbene as a supplement for healthy cognitive aging.

How Does Our Brain Make Long-Term Memories?

There are two key brain regions involved in long-term memory formation. To store memories of names, dates, places, facts, events, and so forth — what’s called declarative memory formation and consolidation — is largely dependent on the hippocampus, a brain region strongly affected by aging. 

Working memory is dependent on the prefrontal cortex, another brain region altered by aging. It is where newly encoded information can be retained for, at most, several hours, followed by a consolidation process that generates a stable long-term memory trace. In this study, La Spina and colleagues aimed at evaluating whether a chronic administration of pterostilbene could improve cognitive performance in aged rats and at assessing pterostilbene-induced molecular modifications in the hippocampus and in the prefrontal cortex.

Pterostilbene Supports Healthy Cognition During Aging

Pterostilbene Supports Healthy Cognition During Aging

The Italian researchers demonstrated that 18-month-old rats — around 60 to 65 in humans — treated with pterostilbene performed better than untreated ones in three key areas related to long-term memory formation.

First, they scored better in assessments of memory stabilization, requiring intact hippocampal function. Second, pterostilbene-treated aged rats showed an improved ability to associate objects with contexts and to discriminate between the object when presented in a changed context and the same object presented in the same context. Third, the animals showed improvements in retaining information derived from the environment, which is the cornerstone of long-term declarative memory.

The Italian researchers found increased levels of genes related to long-term memory in a key learning and memory brain region called the dentate gyrus. One of these genes in particular (PSD-95) is related to the shape and strength in connection between synapses — the sites where electrochemical signals jump from one neuron to another — which are fundamental to the plasticity seen in neural connections required for learning and memory. Pterostilbene also boosted the activity of another cognitive function-related gene called REST, whose activity in the hippocampus is strongly linked to cognitive preservation and longevity during aging.

At the level of proteins, one such molecular machine called CREB — which is needed to drive extensive protein synthesis required for the birth of new neurons in the hippocampus — was also activated by pterostilbene treatment in aged rats. The effects of pterostilbene treatment may extend to the promotion of mitochondrial biogenesis.

Mitochondria are deeply involved in neuronal plasticity and neurogenesis, providing energy in the form of ATP for processes involved in neurite outgrowth. Conversely, a reduction of mitochondrial turnover is associated with poor cognitive health during aging and may be ascribed to alterations in degradative pathways. Memory consolidation may thus be expected to be accompanied by changes in the mitochondrial network.

Most importantly, these changes in gene activity, protein activation, and mitochondrial balance induced by pterostilbene were all linked to improvements in the rats’ ability to solve a maze that tests memory formation.

While these findings suggest that pterostilbene may act directly on neurons, the possibility remains that its behavioral effects may be, wholly or in part, indirect, mediated by an improvement of the oxygen supply to the hippocampus. This compound, like resveratrol, can stimulate vasodilation, leading to increased blood flow.

This is only the second study examining the effect of pterostilbene on cognitive performance carried out with naturally aged rodents, as distinct from other models pertaining to brain health. The findings strongly suggest that moderate and chronically administered doses of pterostilbene may support age-related cognitive health. The results warrant further explorations aimed at the optimization of a potentially very helpful, safe, and cheap nutritional “brain-aid.”


La Spina M, Sansevero G, Biasutto L, et al. Pterostilbene Improves Cognitive Performance in Aged Rats: An in Vivo Study. Cell Physiol Biochem. 2019;52(2):232-239. doi:10.33594/000000017

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