Aging-Induced Decline in Brain Waste Disposal Function Suggests New Treatment Possibilities
The decline in the brain's ability to clear waste due to aging has long been identified as one of the primary causes of major neurodegenerative diseases such as Alzheimer's and Parkinson's disease. This decline becomes particularly pronounced with age, leading to the accumulation of toxic substances in the brain that cause damage to nerve cells. However, recent research suggests the possibility of restoring this age-related decline in brain waste disposal function through medication. This study, conducted by researchers at the University of Rochester, was based on animal experiments and was published on August 15, 2024 (local time) in the journal Nature Aging. Medical news outlet Medical Xpress reported that the findings could mark a significant turning point in the development of new treatments for brain diseases like Alzheimer's and Parkinson's.
Neurodegenerative diseases such as Alzheimer's and Parkinson's are known to occur when toxic substances are not properly removed from the brain. As the brain's waste disposal capacity decreases with aging, the risk of these diseases increases. The accumulation of toxic proteins in nerve cells can eventually lead to nerve damage and cognitive decline. However, this study confirmed that the medication used can reverse the brain's functional decline due to aging. The researchers conducted experiments on aged mice and found that the drug treatment significantly improved the brain's waste disposal capacity.
Restoring Cervical Lymphatic Function to Improve Brain Waste Disposal Rate
Douglas Kelley, a professor at the University of Rochester and one of the study's lead researchers, devised a method to restore the function of the cervical lymphatic vessels to recover the brain's waste disposal ability impaired by aging. The cervical lymphatic vessels play a crucial role in removing waste and toxic substances from the brain to the outside of the body. Professor Kelley stated, "By restoring the function of the cervical lymphatic vessels, we can substantially improve the waste disposal rate in the brain that has been reduced due to aging." He added, "Given that this method can be realized using drugs already in clinical use, it has significant potential to develop into a practical treatment." This study is expected to open up new avenues for the development of treatments for neurological disorders.
Maiken Nedergaard, the study's co-lead researcher, was part of the team that discovered the brain's waste clearance system, known as the glymphatic system, in 2012 and played an essential role in this study as well. The glymphatic system functions by washing away excess proteins generated from neurons and other cells in the brain via cerebrospinal fluid (CSF) after energy has been expended. This system is vital for maintaining brain health, and its impairment can lead to neurodegenerative diseases such as Alzheimer's and Parkinson's. The discovery of the glymphatic system has provided key insights into developing new treatments for these neurological disorders, and this study has created a new breakthrough by showing that the system's function can be restored with drugs.
Restoring Aging-Induced Decline in Lymphatic Function with Medication
In a young and healthy brain, the glymphatic system effectively clears toxic proteins, but as one ages, this system's functionality declines, increasing the likelihood of disease. Particularly, protein waste accumulated in the skull is processed through the lymphatic system to the kidneys via cerebrospinal fluid. However, as aging progresses, the lymphatic system's function deteriorates, leading to a reduced ability to dispose of brain waste. The researchers observed this process using advanced imaging and particle tracking techniques, analyzing in detail how cerebrospinal fluid exiting the brain moves through the cervical lymphatic vessels.
In particular, the researchers recorded not only the flow of cerebrospinal fluid but also measured the pulsation of the lymphangion, a key component of the lymphatic system. The lymphangion acts as a small pump that transports lymph fluid to other parts of the body, with these pumps forming the lymphatic vessels. Professor Kelley explained that the lymphatic system is structured to transport fluid through a network of small pumps, emphasizing the process of how these pumps form the lymphatic vessels. The study found that in older mice, the frequency of lymphangion contraction decreased, and valve failures occurred, significantly slowing the brain's waste disposal rate. These findings suggest that as aging progresses, the lymphatic system's function gradually declines, potentially increasing the risk of neurodegenerative diseases.
Improving Lymphatic Function with Prostaglandin F2α
In their search for a way to restore the function of the lymphangion, which consists of smooth muscle cells lined up in sequence, the researchers found that prostaglandin F2α, a hormone-like compound that assists in smooth muscle contraction, was effective. This drug, already used clinically for various purposes, can be used to restore lymphatic function by promoting smooth muscle cell contraction. The researchers reported that administering prostaglandin F2α to the cervical lymphatic vessels of aged mice restored the contraction frequency of the lymphangion and the flow of cerebrospinal fluid to levels seen in young mice.
Professor Kelley explained, "The cervical lymphatic vessels are located close to the skin surface, making them easily accessible," and emphasized that this study could serve as a foundation for new treatments for neurological disorders associated with aging. He also noted, "The cervical lymphatic vessels play a crucial role in connecting the nervous system and the lymphatic system, facilitating the smooth processing of brain waste." This research has significant potential to evolve into more advanced treatments through future clinical trials in humans.
