Summary: Aging disrupts memory by increasing levels of the protein FTL1 in the hippocampus, new research shows. In mice, excess FTL1 caused neurons to grow abnormally and led to memory decline, while reducing FTL1 reversed these impairments.
Old mice with suppressed FTL1 regained youthful neural connections and performed better on memory tasks. The findings suggest that blocking FTL1 may open a path toward therapies that restore cognitive function in aging brains.
Key Facts
- FTL1 Discovery: Higher FTL1 levels in old brains impair neural connections and memory.
- Reversal Effect: Reducing FTL1 restored youthful brain connectivity and memory in old mice.
- Therapeutic Potential: Targeting FTL1 may enable treatments that reverse age-related decline.
Source: UCSF
Aging is particularly harsh on the hippocampus, the brain region responsible for learning and memory.
Now, researchers at UC San Francisco have identified a protein that’s at the center of this decline.
They looked at how the genes and proteins in the hippocampus changed over time in mice and found just one protein that differed between old and young animals. It’s called FTL1. Old mice had more FTL1, as well as fewer connections between brain cells in the hippocampus and diminished cognitive abilities.
When the researchers artificially increased FTL1 levels in young mice, their brains and behavior began to resemble that of old mice. In experiments in petri dishes, nerve cells engineered to make lots of FTL1 grew simple one-armed neural wires, or neurites, rather than the branching neurites that normal cells create.
But when scientists reduced the amount of FTL1 in the hippocampus of the old mice, they regained their youth. They had more connections between nerve cells, and the mice did 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, which appears in Nature Aging on Aug. 19. “It’s much more than merely delaying or preventing symptoms.”
In old mice, FTL1 also slowed down metabolism in the cells of the hippocampus. But treating the cells with a compound that stimulates metabolism prevented these effects. Villeda is optimistic the work could lead to therapies that block the effects of FTL1 in 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.”
Authors: Other UCSF authors are 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. For all authors see the paper.
Funding: This work was funded in part by 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 (AG081038, AG067740, AG062357, P30 DK063720). For all funding see the paper.
About this genetics, aging, and memory research news
Author: Levi Gadye
Source: UCSF
Contact: Levi Gadye – UCSF
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment” by Laura Remesal et al. Nature Aging
Abstract
Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment
Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age.
Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition.
Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline.
Mimicking an age-related increase in neuronal FTL1 in young mice alters labile iron oxidation states and promotes synaptic and cognitive features of hippocampal aging.
Targeting neuronal FTL1 in the hippocampi of aged mice improves synaptic-related molecular changes and cognitive impairments.
Using neuronal nuclei RNA sequencing, we detect changes in metabolic processes, such as ATP synthesis, and boosting these metabolic functions through NADH supplementation mitigated pro-aging effects of neuronal FTL1 on cognition.
ur data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
Source link
