Scientists unlock potential drug capable of ‘de-aging’ brain, reversing cognitive decline
Jan. 20, 2021, STANFORD, Calif. — As people age, certain cells in the body can become more problematic than others. Scientists at Stanford Medicine compare this to Smokey the Bear suddenly lighting forest fires instead of putting them out. Until now though, researchers didn’t know why the body begins to develop chronic inflammation during old age. They only knew inflammation could lead to cognitive decline in the brain. Now, a new study has discovered that a set of immune cells are to blame — leading to the possibility of a new treatment that will reverse the mental damage of age.
Professor Katrin Andreasson, a neurologist at Stanford University, says myeloid cells go into inflammatory overdrive as people age. These cells in the brain, circulatory system, and peripheral tissues fight off infectious intruders. They also clean up debris such as dead cells or clumps of proteins and provide nutrients to healthy cells.
As organisms age however, the study finds myeloid cells start neglecting their helpful functions and start hunting for nonexistent pathogens instead. This inflammatory function damages otherwise healthy tissue that gets in the cell’s way.
Blocking out inflammation harmful to the brain
In the study, researchers worked on blocking a particular hormone and receptor abundant in myeloid cells. In experiments on older mice and human cell cultures, the treatment not only restored the body’s youthful metabolism, but also reversed age-related mental decline in the mice. The animals saw their recall and navigation skills return to a level on par with younger mice.
The compound helps immune cells called macrophages – guards that patrol the body for signs of attack – function better by boosting their metabolism. It also inhibits the molecule called PGE2 (prostaglandin E2), which appears more and more in older patients and amps up inflammation.
The macrophages of the aging mice had a lower metabolic rate than those of younger peers. They also displayed high quantities of PGE2. The same applied to macrophages taken from human cell cultures of patients over 65 and under 35.
“It’s a double-whammy — a positive feedback loop,” Prof. Andreasson explains.
This buildup causes them to hoard glucose instead of “spending” it on energy production; driving them into an inflammatory rage and wreaking havoc on aging tissues.
“This powerful pathway drives aging. And it can be downshifted,” Andreasson adds.
Ready for human trials?
Tests on human cells showed similar rejuvenation is possible in people. Importantly, study authors did not observe any toxic side-effects in the mice, opening the door to a medication for human patients.
The study, set to appear in the journal Nature, highlights key changes that underpin cognitive decline and suggests the condition may not be permanent. It’s believed reducing inflammation could slow the aging process and stave off frailty, heart disease, cancer, and even the loss of mental sharpness that happens to nearly everyone in their senior years.
The mice in the study received one of two experimental compounds which interfere with PGE2. Researchers also incubated cultured mouse and human macrophages with these substances. The drugs caused the macrophages to metabolize glucose normally, thereby reversing the cells’ inflammatory characteristics.
One of the drugs was effective at reversing cognitive decline even though it doesn’t penetrate the blood-brain barrier. This suggests that just by resetting macrophages outside the brain, this approach can have a profound impact on what goes on inside the brain too.
“This work has implications not only for the preservation of brain health during aging, but also for conditions such as Alzheimer’s or sepsis,” says Dr. Jonas Neher of the German Centre for Neurodegenerative Diseases in a statement to SWNS. Neher was not involved in the study.
According to the Centers for Disease Control and Prevention, around five million Americans dealt with dementia in 2014. That number is projected to reach 14 million in 2060.
SWNS writer Mark Waghorn contributed to this report.