New study provides molecular insight into how memory changes with age

By Samantha Black, Ph.D.

October 18, 2019 -- Researchers from King's College London and The Open University add evidence as to why memory in old age is less flexible than in young adulthood. They published research on October 17, in Current Biology.

Memories are stored in the brain by strengthening connections between synapses in a process called long-term potentiation. Most memory research has focused on the hippocampus due to its critical role in the formation of new memories. Previous research has shown that hippocampal memory formation declines with age. Moreover, memory recall can alter these connections and allow memories to be adapted for new situations. The researchers set out to determine if the memory updating process was affected by age.

The researchers trained young adult (3-4 months) and aged mice (18-22 months) in a fear memory task, finding that age did not affect overall ability to make new memories. However, when analyzing the synapses before and after the memory task, the researchers found fundamental differences between older and younger mice.

The team found that new memories were laid down via a completely different mechanism in older animals compared to younger ones. In aged animals, there is decreased ability for long-term potentiation, requiring that other mechanisms such a multi-innervated dendritic spines (MISs) may be required for memory generation. Further, in older mice the synaptic changes linked to new memories were much harder to modify than the changes seen in younger mice. To confirm differences in molecular levels of MIS in young and aged animals the researchers saw upregulation of synaptic proteins PSD-95 and nNOS. The researchers suggest that the basic biological processes for laying down memories is shared by mammals, so it is likely that memory formation in humans follows the same processes discovered in mice.

"Our results give a fundamental insight into how memory processes change with age. We found that, unlike in the younger mice, memories in the older mice were not modified when recalled. This 'fixed' nature of memories formed in old age was directly linked to the alternative way the memories were laid down, which our research revealed" said lead researcher Professor Karl Peter Giese, from the Institute of Psychiatry, Psychology & Neuroscience at King's.

"Until now it was thought that older people should be able to form memories in just the same way as younger people, so overcoming memory problems would simply involve restoring this ability," added Giese. "However, our results suggest this is not true, and that there is an important biological difference in how memories are stored in old age compared to young adulthood."

The results may have implications for conditions where memory recall is a problem, such as post-traumatic stress disorder (PTSD). Giese suggests that aging should be taken into consideration when treating patients with PTSD, since confronting and modifying traumatic memories is a core feature of some psychological treatments such as trauma-focused cognitive behavioral therapy.

This study was funded by the UK Biotechnology and Biological Sciences Research Council.

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