Common anti-aging drugs may damage brain’s protective coating
2-drug combo causes profound myelin loss, a hallmark of MS, in lab study
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A black lab mouse is held by a scientist. (Photo from iStock)
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In lab studies, a common anti-aging drug cocktail was found to cause a profound loss of myelin, the protective coating around nerve fibers that's damaged in MS.
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The researchers looked at two popular drugs, dasatinib and quercetin, used in combination.
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In mice, worse damage was seen in younger animals, with these findings "warranting caution" for the combo's clinical use, according to the scientists.
A combination of drugs widely used in anti-aging studies seems to compromise the function of the brain’s myelin-making cells and cause profound myelin loss, according to the findings of a new study in mice and lab-grown cells.
The dual treatment, which combines dasatinib and quercetin, also known as D+Q, caused oligodendrocytes — the cells that produce myelin, the protective coating around nerve cells that is damaged in multiple sclerosis (MS) — to shift into an immature, poorly functioning state, the researchers found.
These immature cells were similar to oligodendrocytes seen in MS lesions, areas of damaged tissue in the body’s nervous system that can be seen on imaging scans. As such, these findings may help shed light on the mechanisms of myelin damage, the scientists say.
“When you administer this cocktail to an animal, young or old, the myelin is damaged, which makes it disappear,” Stephen Crocker, PhD, an immunologist at the University of Connecticut School of Medicine, who led the study, said in a university press release detailing the research findings.
Crocker noted that the damage is “even worse in … young animals” than it is in older ones.
The study, “Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum,” was published in the journal PNAS.
The team noted that these data come from lab experiments and have yet to be confirmed in humans. Still, the findings may have “positive implications for understanding disease, while also warranting caution for [the drug combo’s] widespread use clinically,” the researchers wrote.
In MS, the immune system erroneously launches an inflammatory attack against the myelin sheath, which protects nerve cells. When myelin is damaged and lost, which is known as demyelination, it can result in a range of symptoms, such as fatigue, numbness or tingling, difficulty walking or loss of balance, and problems with vision.
Aging increases the risk of disease progression in MS. Because of this, there has been interest in developing treatments that target mechanisms involved in aging, such as senescence, in which old cells stop dividing and functioning properly but do not die.
Senolytics, or medications that remove senescent cells from aged tissues, are being tested in clinical trials as anti-aging medications. But their effects on the brain are still not well understood, according to the researchers.
Testing the effects of popular anti-aging drug combo D+Q
Here, Crocker’s team focused on a popular combination of anti-aging medicines that’s being explored for a range of conditions, including type 2 diabetes and Alzheimer’s disease.
The treatment combines dasatinib, a medication approved to treat leukemia, and the plant-derived supplement quercetin. The combo is also sometimes used off-label as an anti-aging cocktail, although this is discouraged by the medical community.
For their study, the researchers specifically tested D+Q in young and old mice and in oligodendrocytes grown in the lab. Compared with mice given a placebo, mice treated with D+Q developed significant demyelination — which was particularly worse in younger mice.
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.
The most affected area was the corpus callosum, a large bundle of myelinated nerve fibers that connects the two halves of the brain and is essential for communication between them. In treated animals, this structure disappeared, a phenomenon that sometimes happens in people who received chemotherapy and causes what’s commonly known as chemo brain.
When the researchers examined the brain more closely, they found that the oligodendrocytes had not died. Instead, they had shifted into a more immature state, like younger versions of themselves. This means the oligodendrocytes were still present but not functioning properly. Additional analyses found that the cells’ metabolism was disrupted.
“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 said. In addition, the oligodendrocytes showed signs of stress in the endoplasmic reticulum, a structure that helps fold and process proteins.
Interestingly, these changes closely resembled those observed in oligodendrocytes found in MS lesions.
“Due to the resemblance between oligodendrocytes treated with D+Q and those found in MS lesions, D+Q treatment offers a potential method to model an aspect of oligodendrocyte dysfunction relevant to MS,” the researchers wrote. The team is already working to advance their studies.
