Elife: God! Scientists have found that the drug can reverse age-related cognitive decline overnight

Cognitive ability refers to the ability of the human brain to process, store and extract information.
While everyone wants to keep their minds sharp forever, the effects of age on cognitive abilities are a fact that cannot be ignored, especially in older groups, where decreased executive ability and learning and memory skills are common.
a team at the University of California, San Francisco, published a study on eLife entitled "Small product cognitive enhancer reverses age-related-memory in mice", which offers new hope for reversing age-induced neuron, immune, and cognitive dysfunction.
the report is a drug called ISRIB, in which older mice recover quickly after taking several doses of the drug, while the brain and immune cells are re-active, meaning that brain function is improved.
Peter Walter, a professor in the Department of Biochemistry and Biophysics at the University of California, San Francisco and one of the co-authors of the report, said: "The aging brain does not appear to have permanently lost basic cognitive abilities, and the original cognitive resources still exist, but are hampered by a vicious cycle of cellular stress.
ISRIB showed us a way to break this barrier and restore cognitive ability.
"ISRIB is a comprehensive stress response (ISR) inhibitor (inhibitor).
Previously, protein steady-state loss had been shown to be associated with a variety of age-related diseases, including cognitive impairment, while ISR was the signaling center regulatory network induced by protein steady-state disorders, and the key regulatory step was the phosphattation of eIF2, the starting factor for the translation of energies.
The drug's discovery began in a 2013 study by Professor Walter, a bull who has been rooted in cellular stress for decades, trying to find "solutions" from more than 100,000 compounds that can effectively address cognitive decline caused by traumatic brain injury.
is 1,000 times more potency than other molecules, ISRIB stands out from the crowd and is used in subsequent studies.
2018, researchers published an article in Science that shed light on the mechanism by which ISRIB worked, laying the groundwork for further research on the drug.
new study is based on a previous mouse experiment in which researchers found that long-term ISR activity was associated with persistent cognitive and behavioral impairment in patients with traumatic brain injury, and that using ISRIB therapy almost overnight restored normal brain function in mice.
Because traumatic brain injury is often compared to premature aging, the researchers speculated whether cognitive decline caused by aging was also associated with ISR, and whether ISRIB therapy could also improve or even reverse age-related cognitive decline symptoms.
existing studies have shown that ISRs are able to sense different stress states experienced by cells through four kinases, HRI, PKR, PERK, and GCN2, although only the last three kinases are expressed in the mammalian brain.
To identify age-related upstream modification factors for ISR activation, the researchers explored the effects of age and ISRIB dosing on these three kinases and found significant changes in GCN2, which returned to the same level as the brains of young mice after ISRIB is given, meaning that transient ISRIB dosing can affect ISR activation in the brain.
ISRIB administration can affect ISR activation in the brain In further experiments, the researchers found that drug suppression of ISR significantly improved learning ability in older mice by training older mice to perform a difficult exercise to assess whether a decrease in ISR activation affected age-related cognitive impairment, meaning that inhibiting ISR reversed a broad decline in cognitive function.
to understand how ISRIB might improve brain function, the researchers analyzed the cell activity and anatomical structure of the mema of the region of the mouse brain that is critical to learning and memory, one day after ISRIB treatment.
found that the common features of neuron aging disappeared almost overnight, the loss of tyrups decreased, the electrical activity of neurons became brighter, the response to stimuli was more sensitive, and showed greater connectivity to surrounding cells and the ability to form stable connections with each other that usually occurred only in the brains of young mice.
In addition to age-related cognitive decline and traumatic brain injury, ISRIB may also be an effective treatment for diseases such as alzheimer's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Parkinson's disease, down syndrome, according to a review compiled by Walter and colleagues.
low-temperature electron microscope rendering of ISRIB molecules, of course, the toxic side effects of drugs are often a topic of concern.
ISR is an important cell security mechanism, there is a view that interference with ISR may have serious effects.
, however, interference with ISR does not appear to have produced serious adverse reactions.
researchers believe this may be because only a very small amount of ISRIB is needed to regulate ISR, and even the most powerful ISRIB works when cells mobilize ISR to fight diseases such as invasive infectious diseases.
, the researchers seem to have discovered an ideal way to manipulate ISR.