As we get older, our learning and memory functions diminish – and we now know the protein that’s responsible for making this happen.
Researchers at UC San Francisco have identified the culprit – an iron-associated protein known as FTL1 – whose effects impair our cognition throughout the ageing process, and knowing this may be able to help us target it in the treatment of neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease.
“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, published in Nature Aging. “It’s much more than merely delaying or preventing symptoms.”
The brain’s hippocampus is responsible for learning and memory, but is particularly vulnerable to the effects of ageing. The researchers detected an increase in neuronal FTL1 in the hippocampus of older mice, which matched symptoms of diminished cognitive abilities – and fewer connections between brain cells.
To test its effects, scientists artificially boosted FTL1 in young mice. The animals' brains and behaviour began to resemble those of the older mice – with the increase of FTL1 making it harder for the brain’s synapses to form connections, and ultimately meaning that the mice’s memory deteriorated.
Their motor skills and anxiety levels were unaffected, which showed that the cognitive effects were specific to their memory and synaptic function.
When the researchers reduced the amount of FTL1 in the hippocampus of old mice, they saw more connections between nerve cells. The mice performed better on memory tests. Essentially, they became more youthful.
The FTL1 protein plays a role in iron storage and metabolism, keeping long-term levels balanced. As we age, our brain iron metabolism changes and this increases levels of neuronal FTL1.
By reversing the ageing process in the mice’s cognition, this discovery could lead to therapies that block the effects of FTL1 in the brain and restore cognitive function in older people.
"It's always interesting when we find something that seems to drive ageing, and keeping our brains young is one of the most important aspects of staying healthy and active overall as we get older. FTL1 seems to be such a factor," anti-ageing expert Andrew Steele told BBC Science Focus.
"This is fascinating early research, but there are a few steps between this and new brain ageing medicines for humans. This work was in mice, and we'll have to wait and see whether this protein has the same effect in people."
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