Aging severely damages the hippocampus, a part of the brain that plays a central role in learning and memory.
Scientists at the University of California, San Francisco have identified a protein that appears to be responsible for much of this decline.
FTL1 emerges as a major factor in brain aging
To understand age-related changes, researchers tracked changes in genes and proteins in the mouse hippocampus over time. Of all the animals they studied, only one stood out as being consistently different between young and old animals. That protein is called FTL1.
Older mice showed higher levels of FTL1. At the same time, they had fewer connections between neurons in the hippocampus and performed worse on cognitive tests.
How FTL1 changes brain function
When the research team increased FTL1 levels in young mice, the effect was significant. Their brains began to look and function like those of older mice, and their behavior reflected this change.
Laboratory experiments revealed more details. Neurons engineered to produce large amounts of FTL1 developed simplified structures that formed short, single outgrowths instead of the complex branched networks seen in healthy cells.
Reverse memory degradation by lowering FTL1
The most surprising results came when the researchers reduced FTL1 in older mice. The animals showed clear signs of recovery. Increased connections between brain cells and improved performance on memory tests.
“This is truly a reversal of the disorder,” said Dr. Saul Villeda, associate director of the UCSF Bakar Aging Research Institute and lead author of the paper. natural aging. “It’s not just about delaying or preventing symptoms.”
Metabolism leads to new treatments
Further experiments showed that FTL1 also influences how brain cells use energy. In older mice, higher levels of the protein slowed cellular metabolism in the hippocampus. But when the researchers treated these cells with compounds that boost their metabolism, the negative effects were prevented.
Expectations for future brain aging treatment
Villeda believes these findings could pave the way for treatments that target FTL1 and counteract its effects in the brain.
“There are increasing opportunities to mitigate the worst outcomes of old age,” he said. “This is a hopeful time to address the biology of aging.”
Author and funding
Other UCSF authors are Laura Remesal, Ph.D., Juliana Sucharov-Costa, Ph.D., Karishma J.B. Pratt, Ph.D., Gregor Bieri, Ph.D., Amber Phillip, Ph.D., Mason Huang, Ph.D., Turan Agayev, MD, Charles W. White III, Ph.D., Elizabeth G. Wheatley, Ph.D., Brandon R. DeSousa, Ph.D., Isha H. Jiang, and Jason C. Maynard. PhD, Dr. Alma L. Burlingame. See paper for all authors.
This research was funded in part by the Simmons Foundation, the Bakar Family Foundation, the National Science Foundation, the Hillblom Foundation, the Bakar Institute on Aging, Marc Benioff and Lynn Benioff, and the National Institutes of Health (AG081038, AG067740, AG062357, P30 DK063720). See paper for all funding.
