New Research May Help Age-Related Cognitive Function

UCSF study shows great promise.

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The proverb that “with age comes great wisdom” is found in the bible as well as in ancient Greek and Chinese philosophy. Respecting your elders and the knowledge they have accumulated throughout their long lives is something that has been passed down through the ages.

But sadly, memory and mental flexibility start to decline as people age. Now, a new experimental drug, ISRIB, is showing a reversal of age-related declines according to a study, published in December 2020 in eLife, from The University of California San Francisco (UCSF).

This drug, a press release from UCSF claims, has already been shown in lab studies to restore memory after a traumatic brain injury, reverse cognitive impairments in people with Down Syndrome, prevent noise-related hearing loss, as well as actually enhance cognition in animals. 

“ISRIB’s extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological ‘blockage’ rather than more permanent degradation,” Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science said in the press release.

The study showed that ISRIB works by interfering with the body’s Integrated Stress Response which slows down protein cell production if something is wrong like an injury or illness according to The Hill. If this response remains activated, it can lead to problems like an inability to learn new things or to retain memories. ISRB reboots the cells and stops the stress response.

The researchers trained mice to escape from a watery maze by finding a hidden platform; something that is difficult for older mice to do. The mice that received the drug were able to complete the task as well as the younger mice in the control group and much better than the older mice who did not receive the drug, according to the researchers.

The mice were retested several weeks after they received ISRIB to see how long the effects lasted as well as a second test of mental flexibility. The treated mice still performed at higher levels.

To fully understand how this occurred, the researchers studied the activity and anatomy cells in the hippocampus (the brain region that controls memory and learning) after receiving just one dose of the drug, according to the press release, and found that common signatures of neuronal aging had disappeared literally overnight.

“This was very exciting to me because we know that aging has a profound and persistent effect on T cells and that these changes can affect brain function in the hippocampus,” said Rosi in the press release. “At the moment, this is just an interesting observation, but it gives us a very exciting set of biological puzzles to solve.”

The data suggests that the brain does not permanently lose cognitive abilities – something that was commonly believed – but that memory and function are blocked or trapped by cellular stress according to Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. “Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time,” he said.

Further research is needed before ISRIB can be used to treat diseases like Alzheimer’s, dementia, Parkinson’s, and ALS. But, this is a very important first step to beat these dreaded diseases. Reversing cognitive decline and memory loss in otherwise healthy seniors will add to their quality of life and to the lives of others who will be able to share their pearls of wisdom.

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