As we age, our brain’s ability to clear out harmful waste slows down, making us more susceptible to neurological disorders like Alzheimer’s and Parkinson’s. However, recent research in mice suggests that age-related effects on the brain’s waste-clearing process can be reversed.
“This research shows that restoring cervical lymph vessel function can substantially rescue the slower removal of waste from the brain associated with age,” said Douglas Kelley, PhD, a professor of Mechanical Engineering at the University of Rochester Hajim School of Engineering and Applied Sciences. “Moreover, this was accomplished with a drug already being used clinically, offering a potential treatment strategy.” Kelley is one of the lead authors of the study, which appears in the journal Nature Aging, along with Maiken Nedergaard, MD, DMSc, co-director of the University’s Center for Translational Neuromedicine.
In 2012, Nedergaard and her colleagues discovered the glymphatic system, the brain’s unique waste-removal process that uses cerebrospinal fluid to wash away harmful proteins. This finding opens up new possibilities for treating diseases associated with protein buildup in the brain. In healthy, young brains, the glymphatic system effectively removes toxic proteins, but as we age, its efficiency decreases, paving the way for these neurological disorders.
The transportation of protein waste in the cranial cerebrospinal fluid (CSF) to the lymphatic system and eventually to the kidneys for processing is a critical process for maintaining overall bodily health.
Using advanced imaging and particle tracking techniques, recent research has provided a detailed description of the pathway through the cervical lymph vessels in the neck, which is responsible for allowing approximately half of the “dirty” CSF to exit the brain.
Furthermore, in addition to monitoring the flow of CSF, the researchers were able to observe and document the rhythmic pulsation of the lymph vessels in the neck, which aids in the expulsion of CSF from the brain.
“Unlike the cardiovascular system, which has one big pump, the heart, fluid in the lymphatic system is instead transported by a network of tiny pumps,” said Kelley.
These intricate micro-pumps, known as lymphangions, feature valves that prevent reverse flow and are linked in succession to create lymph vessels.
The study revealed that as the mice matured, the contractions decreased in frequency and the valves ceased to function. Consequently, the velocity of contaminated CSF exiting the brains of older mice was 63 percent slower when compared to younger animals.
The team then set out to see if they could revive the lymphangions and identified a drug called prostaglandin F2α, a hormone-like compound commonly used medically to induce labor and known to aid smooth muscle contraction.
The lymphangions are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymph vessels in older mice, the frequency of contractions and the flow of dirty CSF from the brain both increased, returning to a level of efficiency found in younger mice.
“These vessels are conveniently located near the surface of the skin; we know they are important, and we now know how to accelerate function,” said Kelley. “One can see how this approach, perhaps combined with other interventions, could be the basis for future therapies for these diseases.”
Journal reference:
- 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 & Douglas H. Kelley. Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage. Nature Aging, 2024; DOI: 10.1038/s43587-024-00691-3