Researchers have made significant progress in reversing aging-related brain waste accumulation in mice by using an already clinically approved drug. This discovery may provide a new treatment option for neurological disorders like Alzheimer’s and Parkinson’s, which are characterized by the brain’s inability to efficiently clear toxic waste.
These conditions are often exacerbated by aging, as the brain’s waste-clearing abilities diminish with time. The study, published in *Nature Aging*, suggests that restoring waste removal processes could mitigate the effects of these diseases.
The brain’s waste removal system, known as the glymphatic system, was first described in 2012 by Dr. Maiken Nedergaard and her team. This system uses cerebrospinal fluid (CSF) to clear excess proteins produced by neurons and other brain cells during regular activity.
In young and healthy brains, this system efficiently removes harmful proteins like beta-amyloid and tau, linked to Alzheimer’s, and alpha-synuclein, associated with Parkinson’s. However, as people age, the glymphatic system slows down, which can lead to the accumulation of these toxic proteins and the onset of neurological diseases.
In the study, researchers focused on understanding how waste-laden CSF exits the brain through cervical lymph vessels in the neck, where it is eventually processed by the kidneys.
Using advanced imaging and particle tracking techniques, they detailed how this process works, particularly noting the role of tiny pumps in the lymphatic system that help transport fluid. Unlike the cardiovascular system, which has a single heart pump, the lymphatic system relies on a series of microscopic pumps called lymphangions, which keep fluid moving and prevent backflow.
As the mice aged, researchers observed that these lymphangions became less efficient, resulting in a significant decrease in the removal of waste from the brain. The contractions of these pumps became slower, and the valves started failing, reducing the flow of waste-filled CSF by 63 percent in older mice compared to younger ones.
This reduction in waste clearance was linked to the increased buildup of harmful proteins in the brain, contributing to neurological decline.
To counteract this, the researchers applied a drug called prostaglandin F2α, commonly used to induce labor, which helps stimulate smooth muscle contractions.
When applied to the cervical lymph vessels in older mice, the drug increased the contraction frequency and restored the flow of CSF to levels similar to those found in younger mice.
This finding suggests that targeting the lymphatic system could be a promising strategy for developing future therapies aimed at preventing or treating aging-related neurological disorders.
