Researchers have reversed memory loss in aging mice by targeting a protein that builds up in brain cells, pointing toward a potential pathway to counter the cognitive declines of aging.
In a new study, researchers from the University of California, San Francisco, examined a protein called ferritin light chain 1 (FTL1), which was found to accumulate in the brain’s memory center as mice aged.
When they artificially increased the protein in young mice, the animals developed memory impairments. But when they reduced its levels in older mice, their cognitive performance was boosted to levels seen in much younger mice.
The protein is believed to disrupt energy production within cells, essentially starving neurons of the power needed to form and store memories.
FTL1 is linked to normal, age-related memory decline, which includes common cognitive changes that affect nearly everyone as they get older, even without a disease like Alzheimer’s. Focusing on this protein represents a much larger segment of the aging population.
Dr Saul Villeda, associate director of the UCSF Bakar Aging Research Institute and senior author of the paper, said: ‘It is truly a reversal of impairments. It’s much more than merely delaying or preventing symptoms.
Understanding how aging alters brain cells and molecules is crucial to explaining why some people develop neurodegenerative diseases, including Alzheimer’s and other forms of dementia.
Between six and 12 million Americans 65 and up have been diagnosed with mild cognitive impairment (MCI), a precursor to dementia. About a third of those people develop Alzheimer’s disease within five years.
Rebecca, a 48-year-old single mom, was diagnosed with early-onset Alzheimer’s after debilitating cognitive symptoms upended her life
Researchers at the University of California, San Francisco discovered that a protein known as ferritin light chain 1 (FTL1) builds up in the brain’s memory hub of aging mice (stock image)
Using specialized genetic tools and viruses, the scientists either increased or decreased the levels of the FTL1 protein – which is part of the body’s system that stores iron in cells – in the mice’s brains, specifically in the brain’s memory center.
They put the mice through various memory and learning tests, such as mazes and recognizing new objects, to see how these changes affected their cognitive abilities.
After the tests, they examined the mouse brain tissue under microscopes, counting how many connections between brain cells were lost or regained.
They then measured if the brain cells were generating enough energy to function properly and used dyes to see how iron was being stored in the brain cells.
Researchers found that levels of the FTL1 protein were significantly higher in the memory center of old mice compared to young mice. The higher the FTL1 levels in old mice, the worse they performed on memory tests.
When scientists artificially increased FTL1 in young, healthy mice, it made them forgetful. They performed just as poorly on memory tests as old mice.
But when they reduced FTL1 levels in old, forgetful mice, their memory dramatically improved. They started performing like young mice again.
Repeat experiments proved their results were not a fluke. Multiple trial rounds, using different genetic approaches to reduce FTL1, consistently produced the same outcome.
They published their findings in the journal Nature Aging.
An estimated 6 to 12 million Americans aged 65 and older have mild cognitive impairment (MCI). Approximately one-third of these individuals will progress to Alzheimer’s dementia within a five-year period (stock image)
While the findings are promising, the authors cautioned that the research was conducted only in male mice and that human applications remain in the distance.
A process that successfully reverses memory decline in a mouse’s brain may not work the same way, or at all, in the far more complex human brain.
Dementia research has traditionally centered on beta-amyloid and tau proteins, which are known to accumulate in the brain and form clumps and tangles.
The harmful buildup of proteins is exacerbated as the aging brain loses its natural ability to dispose of metabolic waste.
This research significantly broadens the potential pool of people who could benefit from the findings.
Amyloid and Tau research primarily aims to treat or prevent Alzheimer’s disease, but not everyone who ages will get Alzheimer’s.
But for thousands of people today, the reality of cognitive decline is a present and devastating diagnosis.
Rebecca, a 48-year-old single mother from British Columbia, was diagnosed with early-onset Alzheimer’s after months of debilitating cognitive symptoms that disrupted her daily life.
Jana Nelson was 50 when diagnosed with early-onset dementia, following severe personality changes and a sharp cognitive decline that left her unable to solve simple math problems or name colors
She experienced severe memory lapses, most notably forgetting names and mid-conversation blackouts where she would suddenly lose her train of thought entirely.
The episodes progressed beyond simple forgetfulness to a profound inability to process information, such as opening her work laptop and having ‘zero idea how to do my job,’ even when looking at her own training notes.
Meanwhile, Jana Nelson’s diagnosis of early-onset dementia at age 50 was preceded by severe personality changes, going from a laid-back woman to being short-tempered with extreme, unmanageable mood swings.
Her cognitive abilities sharply declined, manifesting as an inability to solve simple math problems like calculating change from five dollars or name different colors. She became unsteady on her feet, began to repeat herself, and struggled profoundly with problem-solving tasks and spatial reasoning, such as fitting a key into a shaped hole or drawing a clock face.
FTL1 research aims to address the mechanisms behind the general, age-related memory decline that affects nearly everyone, even younger adults who begin to experience memory lapses.
Dr Villeda said: ‘We’re seeing more opportunities to alleviate the worst consequences of old age. It’s a hopeful time to be working on the biology of aging.’
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