Researchers at the University of California, San Francisco (UCSF) say they have identified a single protein that may act as a master switch for brain aging — and blocking it could one day reverse cognitive decline.
The study, published in Nature Aging, focused on the hippocampus, the region of the brain responsible for memory and learning. Scientists tracked changes in genes and proteins in this area and found one stood out: a protein known as FTL1.
Mice with higher levels of FTL1 showed the hallmarks of brain aging. Their nerve cells made fewer connections, their metabolism slowed and their memory performance dropped. When researchers artificially increased FTL1 in young mice the animals quickly developed the same impairments seen in old age.
However, when FTL1 levels were reduced in the brains of older mice the results were dramatic. The animals regained sharp memory, grew stronger neural connections and performed better on learning tasks.
“It is truly a reversal of impairments,” said Dr Saul Villeda, associate director of the UCSF Bakar Aging Research Institute and senior author of the study. “It’s much more than merely delaying or preventing symptoms.”
The findings suggest that therapies designed to target FTL1 could eventually provide a way to restore cognitive function not just slow decline. Villeda said the next challenge is translating the results into treatments that are safe and effective for humans.
“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 work was supported by several research bodies including the National Institutes of Health, the Bakar Aging Research Institute and the Simons Foundation.
References
Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J. B. Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W. White, Elizabeth G. Wheatley, Bende Zou, Brandon R. Desousa, Julien Couthouis, Isha H. Jian, Xinmin S. Xie, Yi Lu, Jason C. Maynard, Alma L. Burlingame, Saul A. Villeda. Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment. Nature Aging. 19 August 2025. doi:10.1038/s43587-025-00940-z
