Mitochondria are essential for cellular health, acting as the cell’s powerhouses. When damaged, they are cleared through mitophagy, vital for the function of long-lived cells, particularly in the brain.
Impaired mitophagy has been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, making it a key target for drug development and therapeutic research.
New research from the McWilliams Lab at the University of Helsinki, led by doctoral researcher Anna Rappe, reveals a dynamic and unexpected pattern of mitophagy in different brain cell types as animals age. In a specialized brain region responsible for movement, mitophagy levels increased with age, while in memory-related brain cells, mitophagy initially rose but sharply declined in old age.
These findings highlight midlife as a critical point for healthy brain aging and provide new insights into the molecular mechanisms that support brain function.
Another important discovery was that some lysosomes, which break down cellular waste, lose acidity as the brain ages. This change mirrors observations in Alzheimer’s disease models, suggesting that normal aging processes may be worsened in neurodegenerative diseases.
The study challenges the previous belief that mitophagy declines with age, showing that the process is more complex and dynamic in longer-lived mammals than previously thought.
For this study, the team used cutting-edge mouse genetics, optobiology, neuroscience, and advanced imaging tools to track mitophagy over time in different brain cell types. Their results highlight the importance of developing new perspectives when studying brain aging in longer-lived species, with midlife emerging as a critical period for preserving brain function.
Associate Professor Thomas McWilliams said, “There is no doubt that mitophagy decreases in shorter-lived species. While we share important genes and mechanisms, the tissues of longer-lived mammals have evolved under distinct pressures to handle different challenges. Our work reveals that mitophagy is highly dynamic in the aging mouse brain and suggests midlife is a crucial period for mammalian brain health.”
Despite progress in understanding neurodegenerative diseases, the high failure rate of current therapies highlights the urgent need for new approaches.
Dr. Anna Rappe and her team are excited by their recent findings, which offer a fresh perspective on brain aging. Working alongside clinical collaborators, they aim to advance this research into more human-centered applications. The team hopes their results will provide a valuable roadmap for companies and translational researchers, helping to accelerate the development of new therapies for brain diseases.
Journal Reference:
- Anna Rappe, Helena A Vihinen, Fumi Suomi, Antti J Hassinen, Homa Ehsan, Eija S Jokitalo, Thomas G McWilliams. Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging. The EMBO Journal, 2024; DOI: 10.1038/s44318-024-00241-y
