Date: October 28, 2024
Source: University of California – Los Angeles
Researchers at UCLA have uncovered a promising new path toward slowing cognitive decline. Their study, published in Nature Communications, reveals that a protein called filamentous actin, or F-actin, accumulates in aging fruit fly brains, impairing the cellular “waste disposal” system that keeps brain cells functioning well. This buildup appears to accelerate cognitive decline and overall aging. Remarkably, by genetically preventing F-actin buildup, researchers were able to improve brain function and increase the healthy lifespan of fruit flies by about 30%.
Brain Decline Linked to Cellular Waste Accumulation
The UCLA team, led by Edward “Ted” Schmid and Professor David Walker, found that F-actin, a structural protein, builds up in brain cells as fruit flies age, blocking autophagy—the cell’s ability to clear out damaged or unnecessary components like DNA, lipids, proteins, and cellular organelles. This waste buildup hinders neurons and accelerates brain aging.
“Flies become forgetful as they age, just as humans do,” said Walker, UCLA professor of integrative biology and physiology. “Preventing F-actin buildup allowed older flies to retain learning and memory functions, pointing to a direct link between F-actin and cognitive health.”
Key Findings and Methods
The team discovered two major indicators that F-actin accumulation could be related to aging: fruit flies on restricted diets, which generally live longer, had lower F-actin levels in their brains, and flies treated with the drug rapamycin, known for lifespan extension, also showed reduced F-actin buildup. To establish causation, the researchers used genetic tools to specifically target genes associated with F-actin production, like the Fhos gene, to reduce the protein’s accumulation in the brain.
By decreasing Fhos expression in neurons, the team prevented F-actin buildup. The result? Flies not only maintained cognitive function but also showed improvements in other organ systems, suggesting a broad impact on health.
Cellular “Garbage Disposal” Revitalized
Further analysis indicated that F-actin buildup directly interferes with autophagy. Without an active “cellular garbage disposal,” brain cells accumulate waste, which speeds up cellular aging. When the researchers removed F-actin but blocked autophagy, aging effects persisted, suggesting that F-actin’s primary aging mechanism is its interference with autophagy.
The findings suggest that preserving autophagy could delay age-related cognitive decline, making this pathway a compelling target for age-related therapies in humans.
Implications for Human Aging and Cognitive Health
Although the study was conducted on fruit flies, the research opens doors for future studies on age-related cognitive decline in humans. Since humans share similar cellular processes, blocking F-actin buildup might protect aging human brains from cognitive impairment and neurodegenerative diseases.
“Much of our aging research is focused on healthspan—years of good health—as well as lifespan,” Walker emphasized. “If we could apply similar genetic or pharmacological methods in humans, we might be able to help people live healthier, longer lives.”
Moving Forward: Exploring Human Applications
Future research will examine F-actin’s role in other organisms to see if similar results apply beyond flies. By studying whether diet, lifestyle changes, or drugs like rapamycin can reduce F-actin in humans, researchers hope to uncover ways to naturally protect brain health.
Study Support and Acknowledgments
This work was funded by the National Institute on Aging of the NIH. Researchers anticipate that the study’s insights into cellular processes could drive new treatments to extend not just lifespan but also the quality of life in later years.
Journal Reference: Edward T. Schmid, Joseph M. Schinaman, Naomi Liu-Abramowicz, Kylie S. Williams, David W. Walker. Accumulation of F-actin drives brain aging and limits healthspan in Drosophila. Nature Communications, 2024; 15 (1).DOI: 10.1038/s41467-024-53389-w