Since time immemorial, people who have been fortunate enough to live a long life, have suffered toward the end of that span. They gradually lose the memories that they could quickly and easily call up when they were younger. Names, facts, and places become progressively harder to access and bring into conscious awareness. It has been widely accepted that this is just the natural order of things. People are born, grow to maturity, reach the height of their powers in adulthood, and then decline into old age and death. Nothing new here. It has always been this way. But just because it has always been this way does not mean that it must necessarily be this way.

If a human being, or really, any animal, reaches a peak of robust health, either physically or mentally, but then goes into decline, there must be a reason, a biological reason, for that decline. Whatever that reason is, if it can be identified, perhaps it can be countered or even eliminated.

There are probably multiple factors that contribute to the fading of memory that people experience as they age. Some of the suspect causes include protein synthesis, metabolism, inflammation, and immune responses. What each of these processes contribute has been unclear, but it has been known for many years, that a decline in protein synthesis plays a role. Misfolded proteins in the brain are not replaced in a timely manner as they should be, and they trigger the integrated stress response (ISR). Recent work, documented in this preprint from the lab of Susanna Rosi at the University of California at San Francisco, points to ISR having a causative role in cognitive decline.

Professor Rosi’s team countered the ISR in lab mice with a small molecule inhibitor named ISRIB. ISRIB was known to rescue traumatic brain injury behavioral and cognitive deficits. Rosi’s team reasoned that ISRIB might also rescue old mice from the cognitive decline due to aging. To test that hypothesis, several experiments were conducted. Old mice that had been injected with ISRIB on three successive days, were compared to age-matched control mice as well as young mice. All the test subjects were then placed in a water maze.

A water maze is a fiendish device that researchers use to test the cognitive power of murine test subjects. The water in it is deep enough to drown a mouse if it stops swimming, and it is dyed so that the mice cannot see what is beneath the surface. The maze has multiple branches, all but one of which lead to a dead end. The one branch that is not a dead end contains an underwater platform upon which the mouse can rest. Motivated by the threat of death by drowning, the mice must swim from one branch to another until they find the one with the platform.

After the mice take training runs to learn how to find the platform, they are tested for how well they remember where the platform is.

• The young mice, as expected, swam down the fewest dead-end maze branches before finding the one with the platform.
• The old mice who are given a sham injection on three successive days, with no ISRIB, swam down more dead-end branches, signifying impaired memory compared to the young mice.
• The old mice that had received ISRIB injections on three successive days performed significantly better than the old control mice, which had received sham injections. Their performance was close to that of the young mice.

Other tests showed that the mice that received the ISRIB treatment retained their cognitive advantage for at least 23 days, with no additional treatment.

This is exciting. ISR may not be the only cause of cognitive decline due to aging, but if it is a contributor, and if it can be remedied by a small molecule such as ISRIB, this seems like something deserving follow-up. If elderly people in care homes with cognitive deficits could recover their wits and return to normal life, it would be a life-changing boon for those affected as well as for those who care about them. It would also save huge amounts of money now spent on caring for people who cannot care for themselves.

BIO:

Allen G. Taylor is a 40-year veteran of the computer industry and the author of over 40 books, including Develop Microsoft HoloLens Apps Now, Get Fit with Apple Watch, Cruise for Free, SQL For Dummies, 9th Edition, Crystal Reports 2008 For Dummies, Database Development For Dummies, Access Power Programming with VBA, and SQL All-In-One For Dummies, Third Edition. He lectures internationally on astronomy, databases, innovation, and entrepreneurship. He also teaches database development and Crystal Reports through a leading online education provider. For the latest news on Allen’s activities, check out his blog at wwwallengtaylor.com or contact him at allen.taylor@ieee.org.