Researchers at the University of California, San Francisco (UCSF) have identified a protein that plays a key role in age-related decline in the hippocampus, a brain region important for learning and memory. The study, published in Nature Aging on August 19, focused on how genes and proteins change in the hippocampus over time in mice.
The team found that levels of a protein called FTL1 were higher in older mice compared to younger ones. This increase was linked to fewer connections between brain cells and reduced cognitive abilities. When researchers artificially raised FTL1 levels in young mice, their brains and behavior began to resemble those of older animals. In laboratory experiments, nerve cells engineered to produce high amounts of FTL1 grew simpler neural structures rather than the more complex branching typically seen.
Reducing FTL1 levels in the hippocampus of old mice led to improvements. These mice showed more connections between nerve cells and performed better on memory tests.
“It is truly a reversal of impairments,” said Saul Villeda, PhD, associate director of the UCSF Bakar Aging Research Institute and senior author of the paper. “It’s much more than merely delaying or preventing symptoms.”
The study also found that FTL1 slows metabolism in hippocampal cells. However, treating these cells with a compound that stimulates metabolism counteracted these effects. Villeda expressed hope that this research could lead to therapies targeting FTL1’s impact on the brain.
“We’re seeing more opportunities to alleviate the worst consequences of old age,” he said. “It’s a hopeful time to be working on the biology of aging.”
Other contributors from UCSF include Laura Remesal, PhD; Juliana Sucharov-Costa; Karishma J.B. Pratt, PhD; Gregor Bieri, PhD; Amber Philp, PhD; Mason Phan; Turan Aghayev, MD, PhD; Charles W. White III, PhD; Elizabeth G. Wheatley, PhD; Brandon R. Desousa; Isha H. Jian; Jason C. Maynard, PhD; and Alma L. Burlingame, PhD.
The research received funding from several sources including the Simons Foundation, Bakar Family Foundation, National Science Foundation, Hillblom Foundation, Bakar Aging Research Institute, Marc and Lynne Benioff, and the National Institutes of Health.
