Popular anti-aging drug combo caused severe brain damage in mice

The findings, published in PNAS, showed that the drug pairing dasatinib+quercetin (D+Q) damaged myelin, the protective coating that surrounds nerve fibers and helps electrical signals travel efficiently through the brain and body.

"When you administer this cocktail to an animal, young or old, the myelin is damaged, which makes it disappear. Even worse in the young animals" than in the aged ones, says UConn School of Medicine immunologist Stephen Crocker.

Myelin loss can lead to numbness, pain, difficulty walking, and problems with memory and thinking. Damage to myelin is also a defining feature of multiple sclerosis.

Anti-Aging Drugs and Brain Health Concerns

D+Q has become one of the most popular drug combinations in anti-aging research. Scientists have investigated it for its ability to remove aged cells that contribute to inflammation and age-related disease. The treatment is currently being explored for conditions including type II diabetes and Alzheimer's disease.

Outside clinical settings, some people interested in longevity have also experimented with the drugs on their own, despite warnings from medical professionals. However, very little research has examined how the combination affects the brain.

Researchers Evan Lombardo '23 (CLAS), now a neuroscience graduate student at Dartmouth, and Robert Pijewski '21 Ph.D., currently at Anna Maria College, wanted to see whether D+Q might help repair brain damage associated with multiple sclerosis.

To test the idea, the team treated both young mice (6 to 9 months old) and older mice (22 months old) with the drug combination. They also studied oligodendrocytes grown in laboratory dishes. These specialized brain cells are responsible for producing and maintaining myelin.

Severe Myelin Loss and "Chemo Brain" Effects

The results surprised the researchers.

Healthy mice normally show thick myelin layers surrounding nerve fibers in the brain. In the treated mice, those protective layers were dramatically reduced after exposure to D+Q. Younger mice experienced even greater damage than older animals.

The researchers also found that the corpus callosum, a major structure that connects the two halves of the brain and supports many critical functions, had deteriorated in mice receiving the treatment. Similar damage is sometimes seen in people undergoing chemotherapy and is associated with symptoms often described as "chemo brain."

Brain Cells Reverted to an Immature State

When scientists examined the damaged tissue more closely, they discovered that the oligodendrocytes had not died. Instead, the cells appeared to regress into a more juvenile form.

The team also observed abnormal metabolism inside the cells.

"We suspect the drugs are choking off energy the cells need, and the cells respond by reducing complexity, reverting to a younger state, but less functional," Crocker says.

Interestingly, the altered cells closely resembled a distinct population of cells previously identified in people with multiple sclerosis. The researchers believe this could provide important clues about how the disease develops.

New Clues About Multiple Sclerosis

The findings suggest that in multiple sclerosis, myelin-producing cells may come under stress and revert to a younger, less functional state instead of dying completely. If true, that could mean the cells still have the potential to recover.

Researchers are now investigating whether those damaged cells can be restored and encouraged to repair the brain.

"If we can mimic this, we have an amazing opportunity to see if the cells can recover and repair the brain," Crocker says.