Jump to content
Sign in to follow this  
corybroo

ISRIB reversed memory & mental flexibility overnight in mice

Recommended Posts

Drug reverses age-related cognitive decline within days

Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice

The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome , prevent noise-related hearing loss, fight certain types of prostate cancer , and even enhance cognition in healthy animals.

researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.

The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress

ISRIB, discovered in 2013 in Walter's lab, works by rebooting cells' protein production machinery after it gets throttled by one of these stress responses—a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).

recent animal studies … have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.

The cognitive deficits in TBI patients are often likened to premature aging, which led Rosi and Walter to wonder if the ISR could also underlie purely age-related cognitive decline. 

Several weeks after the initial ISRIB treatment, they trained the same mice to find their way out of a maze whose exit changed daily—a test of mental flexibility for aged mice who, like humans, tend to get increasingly stuck in their ways. The mice who had received brief ISRIB treatment three weeks before still performed at youthful levels, while untreated mice continued to struggle.

the researchers studied the activity and anatomy of cells in the hippocampus, a brain region with a key role in learning and memory, just one day after giving animals a single dose of ISRIB. They found that common signatures of neuronal aging disappeared literally overnight: neurons' electrical activity became more sprightly and responsive to stimulation, and cells showed more robust connectivity with cells around them while also showing an ability to form stable connections with one another usually only seen in younger mice.

Share this post


Link to post
Share on other sites

It sounds like Alphabet’s Calico has an interest in ISRIB.

Calico’s memory-enhancing drug reverses age-related mental decline

Longevity.Technology: ISRIB is licensed by Calico, the well-funded, but enigmatic arm of Alphabet, Google’s parent company, which researches the biology of aging. This new research indicates that ISRIB reverses the integrated stress response in the brain and mitigates age-related cognitive decline, albeit only in mice so far. If this indication can also be shown in humans, Calico would have a licence that dovetails with their mission to “discover and develop interventions that enable people to live longer and healthier lives”.

Saul, what is a "sall study"?

Share this post


Link to post
Share on other sites

Create an account or sign in to comment

You need to be a member in order to leave a comment

Create an account

Sign up for a new account in our community. It's easy!

Register a new account

Sign in

Already have an account? Sign in here.

Sign In Now
Sign in to follow this  

×