This Protein Slows the Aging Brain, and We Know How to Counter It
The findings raise the possibility of new treatments for aging-related cognitive decline.
Artificial neurons grown in petri dishes will grow branching wires, or neurites, with several “arms.” When these same neurons were engineered to produce a lot of FTL1 protein, their neurites became much simpler, rarely branching out. Credit: Remesal et al., Nature Aging.
Aging is particularly harsh on the hippocampus, the brain region responsible for learning and memory. Now, a team led by researchers at UC San Francisco and including Yi Lu, a professor of chemistry at The University of Texas at Austin, have identified a protein that’s at the center of this decline. Their findings, published today in the journal Nature Aging, raise the possibility of new treatments for aging-related cognitive decline.
This work was funded in part by the National Science Foundation, the National Institutes of Health, Simons Foundation, Bakar Family Foundation, Hillblom Foundation, Bakar Aging Research Institute, and Marc and Lynne Benioff.
The researchers 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, 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.”
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,” said Villeda, Endowed Professor of Biomedical Sciences. “It’s a hopeful time to be working on the biology of aging.”
Adapted from a press release by the University of California San Francisco.
