UC San Francisco researchers have discovered a surprising guilty in brain aging: a protein called FTL1.
In aged mice, too much of this protein weakened the memory and interrupted neuronal connections. But when the scientists blocked FTL1, the brains of the mice recovered the youth function, and their memory tests improved dramatically.
Aging hits hard hippocampus
Aging has a great cost in the hippocampus, the part of the brain that drives learning and memory.
UC San Francisco scientists have now identified a single protein, FTL1, which seems to play a central role in this decline related to age.
When studying how genes and proteins in the hippocampus change over time in mice, the team discovered that only one stood out as constantly different among young and old animals: FTL1.
Imitating old age in young brains
The oldest mice showed higher levels of FTL1, less connections between the hippocampus neurons and the weakest memory performance. When researchers artificially increased FTL1 in young mice, their brains and behavior quickly began to resemble those of much older animals.
In cell culture experiments, neurons designed to produce large amounts of FTL1 developed abnormally. Instead of growing complex and branched neurites, they only formed simple extensions of a single assembly.
Reversion of the decrease in memory down FTL1
When scientists reduced FTL1 in the aged mice hippocampus, the results turned. Their neurons made more connections and the animals improved significantly in memory tests.
“It is really a reversal of the impediments,” said Saul Villeda, PHD, associate director of the Bakar Avejement Research Institute of UCSF and main author of the document, which appears in Aging of nature on August 19. “It is much more than simply delaying or preventing symptoms.”
Metabolism, FTL1 and Hope of Therapies
In old mice, FTL1 also slowed metabolism in hippocampus cells. But the treatment of cells with a compound that stimulates metabolism avoided these effects.
Villeda is optimistic that work could lead to therapies that block the effects of FTL1 on the brain.
“We are seeing more opportunities to relieve the worst consequences of old age,” he said. “It is a hopeful moment to work on the biology of aging.”
Reference: “Targeting Iron-Associated Protein FTL1 in the Brain of Old Mice Improvs Age-Related Cognitive Impairment” by Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma JB Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W. White III, Elizabeth G. Wheatley, Bende Zou, Brandon R. Desuse, Julien Couthouis, Isha H. Jian, Xinmin S. Xie, Yi Lu, Jason C. Maynard, Alma L. Burlingame and Saul A. Villeda, August 19, 2025, Aging of nature.
DOI: 10.1038/S43587-025-00940-Z
Authors: Other UCSF authors are Laura Remesal, PHD, Juliana Sucharov-Costa, Karishma JB Pratt, PHD, Gregor Bieri, PHD, Amber Philp, PHD, Mason Phan, Turan Aghayev, MD, PHD, Charles W. White III, PHD, Elizabeth G. Wheatley, PHD, PHD, PHD, PHD, ISHA H. JIAN, WHITE, PHD, ELIZABETH G. WHEATLEY, PHD, PHD, PHD, PHD, ISLAND, ISLAND, ISLAND, III, PHD, ELIZABETH G. WHEATLEY, PHD, PHD, PHD, PHD, PHD, Elizabeth G. Wheatley, PHD, PHD, PHD, PHD, ISLAND, ISLAND, ISH. Jason C. Maynard, PHD, and Alma L. Burlingame, PHD.
Financing: This work was financed by the Simons Foundation, Bakar Family Foundation, National Science Foundation, Hillblom Foundation, Bakar Aging Research Institute, Marc and Lynne Benioff, and the National Health Institutes (AG081038, AG067740, AG062357, P30 DK063720).
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