Researchers at UC San Francisco have identified a protein, FTL1, that appears to play a central role in the aging of the hippocampus, a brain region important for learning and memory. The study compared gene and protein changes in the hippocampus of young and old mice, finding that FTL1 was present at higher levels in older animals. These older mice also had fewer connections between brain cells and showed reduced cognitive abilities.
Increasing FTL1 artificially in young mice led their brains and behavior to resemble those of old mice. In laboratory experiments, nerve cells engineered to produce more FTL1 developed simpler neurites instead of the usual branching structures seen in healthy cells.
Reducing FTL1 levels in the hippocampus of old mice reversed these effects. The older mice regained more neural connections 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 published in Nature Aging on August 19. “It’s much more than merely delaying or preventing symptoms.”
The study also found that high levels of FTL1 slowed metabolism within hippocampal cells. However, treating these cells with a compound that stimulates metabolism prevented these effects. Villeda expressed optimism about future therapies targeting FTL1.
“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 authors from UCSF contributed to this research, which received funding from organizations including the Simons Foundation, Bakar Family Foundation, National Science Foundation, Hillblom Foundation, Bakar Aging Research Institute, Marc and Lynne Benioff, and several grants from the National Institutes of Health.
