This project focuses on the brain’s “glycocalyx”—a complex network of sugars on the cell surface, which plays a crucial role in many brain functions including how neurons connect and communicate and how memories are formed and stored. Despite the glycocalyx’s importance in the brain’s response to aging and neurodegenerative diseases like Alzheimer’s, the exact roles and changes of the glycocalyx throughout life are poorly understood.
The ketogenic diet, fasting, and ketone supplements switch the body's fuel source from carbs to fats, a state known as ketosis. This switch can be good for your brain, helping to keep it healthy and resilient to damage. In ketosis, your liver makes a special fat-derived fuel called beta-hydroxybutyrate (BHB). BHB is like a cleaner fuel for your brain—it doesn't leave as many harmful leftovers as sugar does, and it can also tell your brain to turn on defense mechanisms.
Myelin, traditionally thought of as the brain's electrical insulator, has emerged as an active and dynamic regulator of brain functions including neuroprotection, learning, and memory. Myelin dysfunction and loss is increasingly found to be central to brain aging and neurodegenerative diseases including Alzheimer's. However, the causes of myelin dysfunction and loss in the aged or diseased brain remain unknown, precluding therapies to promote its preservation and proper function.
This team aims to use the power of artificial intelligence to make new findings about brain aging, with the goal of boosting brain repair and resilience. They are particularly interested in spatial changes in the brain during aging. Their goal is to understand how aging renders the brain susceptible to injuries that accentuate neurodegenerative diseases. This is an underexplored question because brain injuries are usually not studied from the standpoint of age, and this viewpoint should identify new ways to boost brain repair and resilience.
Neuroinflammation is common in several neurodegenerative diseases, with brain immune cells, specifically microglia, being a main driver of the inflammatory process. Understanding what triggers microglial activation and its pathways will lead to a better knowledge of inflammatory mechanisms involved in neurodegenerative disease pathology. Circular RNAs (circRNAs) have been studied extensively in the peripheral immune system due to their ability to induce innate immune responses.
This team will study the brains of individuals who lived past ninety with their cognitive function intact, using advanced tissue imaging and computer science to understand mechanisms of resilience that could slow neurodegeneration and preserve brain health.
This team aims to discover whether the brain’s endocannabinoid system is dysregulated during aging, triggering inflammation via molecules called prostaglandins. If so, a drug that decouples these systems might restore a youthful brain state and rescue cognitive function.
This team plans to study whether changes in neurons in the midbrain that regulate sleep, wakefulness, and immunity could contribute to aging and neurodegeneration. If successful, this information could rescue deficits in sleep and restore a normal immune profile.
Using new animal models such as the African killifish, this team aims to develop approaches to predict individual brain aging trajectories early in life based on behaviors that can be modulated to promote healthy memory, executive function, and processing speed as well as to counter dementia.
This team aims to define how and why protein production breaks down in aging cells, leading to disease. This research may lead to new diagnostic and therapeutic approaches against neurodegenerative diseases and potentially aging itself.