Researchers at the University of California, San Francisco report that higher levels of the iron-associated protein FTL1 in the hippocampus of older mice are tied to weaker neural connections and worse performance on cognitive tests. In the experiments, reducing FTL1 in older mice was associated with increased neuronal connectivity and improved memory performance, findings published in Nature Aging.
Scientists at the University of California, San Francisco tracked changes in genes and proteins in the hippocampus of mice as they aged and identified FTL1 as the protein that most consistently differed between young and old animals, according to a research summary released by the university.
In older mice, the researchers reported higher levels of FTL1 alongside fewer connections between neurons in the hippocampus and poorer performance on cognitive tests. In a separate set of experiments, boosting FTL1 in young mice caused the animals’ brains and behavior to resemble those of older mice. In lab experiments, neurons engineered to produce high amounts of FTL1 developed simplified structures, forming shorter, less complex extensions.
The team also reported a metabolic link: higher FTL1 levels in older mice were associated with slower cellular metabolism in the hippocampus. When researchers treated cells with a compound described as boosting metabolism, they found the negative effects were prevented.
The most dramatic effects were reported when FTL1 was reduced in older mice. The researchers said connections between brain cells increased and performance on memory tests improved.
“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.”
Villeda said the work could point to future approaches aimed at countering age-related brain decline. “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.”
The paper is titled “Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment,” and was published in Nature Aging. The university said the work was funded in part by the Simons Foundation, the Bakar Family Foundation, the National Science Foundation, the Hillblom Foundation, the Bakar Aging Research Institute, Marc and Lynne Benioff, and the National Institutes of Health.
