A recent study published in Nature Aging has shown that it is possible to reverse age-related slowing of brain waste clearance, a key process that may contribute to neurological diseases like Alzheimer’s and Parkinson’s. Using a drug already approved for clinical use, researchers were able to restore this waste-clearing function in older mice, bringing it back to the efficiency seen in younger brains. The findings offer a potential pathway for developing treatments that target brain waste removal, which could delay or mitigate the effects of age-related neurological disorders.
Neurological diseases such as Alzheimer’s and Parkinson’s are often linked to the accumulation of toxic proteins in the brain. Over time, these proteins build up due to a failure of the brain’s waste removal system, which clears out harmful substances. In younger individuals, this system, known as the glymphatic system, works efficiently to wash away these toxic proteins using cerebrospinal fluid (CSF). However, as people age, the brain’s ability to clear out waste slows down, increasing the risk of diseases associated with this toxic buildup.
Researchers have long suspected that the lymphatic system—the network of vessels that remove waste from the body—may play a critical role in this process. Specifically, lymph vessels in the neck are believed to help remove CSF loaded with waste from the brain. But as the body ages, these vessels lose their ability to function properly. This study aimed to determine whether it was possible to restore their function and, by extension, the brain’s waste removal capabilities.
“The circulation of water-like fluid through and around brain tissue clears away wastes whose buildup correlates with diseases like Alzheimer’s and Parkinson’s. Those diseases are more likely in older patients, and many studies have shown that waste is cleared more slowly in older animals. We wondered if the lymph vessels in the neck, which take fluid from the skull, might play a role, and if we could counteract some effects of aging,” said Douglas H. Kelley, a professor of mechanical engineering at the University of Rochester.
To investigate, the researchers focused on a particular set of lymph vessels in the neck, known as cervical lymph vessels. These vessels drain approximately half of the brain’s waste-laden cerebrospinal fluid into the body’s lymphatic system, where it is ultimately processed and eliminated. The study used advanced imaging techniques to observe and measure how efficiently these vessels worked in younger and older mice.
The researchers tracked the flow of CSF from the brain through the cervical lymph vessels, paying close attention to the way the vessels pulsed, which helps to pump the fluid. In young mice, the vessels contracted regularly and efficiently, but in older mice, the vessels were less active, contracting less frequently and with reduced strength. This resulted in a 63% slowdown in the removal of CSF from the brain in older mice compared to younger ones.
After documenting the decline in function, the research team wanted to see if they could restore the activity of these aging lymph vessels. They used a drug called prostaglandin F2 alpha, a hormone-like compound that stimulates smooth muscle contractions. This drug is already in medical use to induce labor and has a known effect on smooth muscle tissue, which lines the lymph vessels.
By applying prostaglandin F2 alpha to the cervical lymph vessels, the researchers were able to restore the vessels’ ability to pump CSF out of the brain as efficiently as in younger animals. This finding suggests that it may be possible to develop treatments that target this mechanism, potentially offering a way to slow or prevent the buildup of toxic proteins in the brain and delay the onset of neurological diseases.
“As mice get older, neck lymph vessels don’t work as well to clear brain waste, but a muscle-stimulating drug (prostaglandin 4 alpha) can make old vessels pump fluid as well as young ones,” Kelley told PsyPost. “Personally, I was surprised and impressed that the effect of the drug was so strong!”
While the study offers promising insights into how brain waste clearance might be restored in aging populations, there are several important limitations to consider. The study was conducted in mice, and it is unclear whether the same results would apply to humans. While the underlying mechanisms of brain waste clearance and lymph vessel function are likely to be similar, further research will be necessary to confirm whether the same approach would work in people.
“We worked only with mice, so many more trials will be necessary before human patients see similar treatments,” Kelley noted. “We applied the drug directly to the lymph vessels, during surgery, so developing an ointment, pill, or injection would make it more convenient.”
Additionally, while the drug successfully restored lymph vessel function in the study, it is unclear how long the effects would last or whether repeated treatments would be necessary. The researchers also noted that combining this approach with other interventions might be even more effective.
While much work remains to be done before this approach can be applied to humans, the findings point toward a promising new strategy for combating diseases that have long been linked to aging and toxic protein buildup in the brain. Kelley said the long-term goal is to “help prevent or alleviate diseases like Alzheimer’s and Parkinson’s by improving brain waste clearance.”
The study, “Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage,” was authored by Ting Du, Aditya Raghunandan, Humberto Mestre, Virginia Plá, Guojun Liu, Antonio Ladrón-de-Guevara, Evan Newbold, Paul Tobin, Daniel Gahn-Martinez, Saurav Pattanayak, Qinwen Huang, Weiguo Peng, Maiken Nedergaard, and Douglas H. Kelley.