Memory generally begins to decline slowly after the brain reaches its peak capacity before the age of 30. Although researchers understand many of the mechanisms involved in creating and maintaining memories, the molecular causes of normal age-related memory loss remain unclear.
A study published in Cell offers a possible explanation. Researchers examined the brains of 10 million fruit flies at eight stages of life, from the first day after hatching to 35 days of age, a stage comparable to old age in the insects. The six-year project is described as one of the largest investigations of its kind.
The work focuses on Funes, a protein named after Funes the Memorious, the character created by Argentine writer Jorge Luis Borges. Funes belongs to the chaperone family, whose members help proteins fold into the three-dimensional shapes needed for them to function correctly.
The researchers found that increasing Funes production in older flies caused amyloid proteins involved in memory to move toward more youthful states. The flies also showed improved memory. In contrast, increasing production of another chaperone, CG6693, had the opposite effect: young flies accumulated misfolded amyloids and performed worse in memory tests.
Amyloids are often associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, the study adds to evidence that some amyloids are soluble and beneficial, helping form and preserve long-term memories rather than creating harmful plaques. One example is Orb2, whose atomic structure was previously described by the same research line.
The findings suggest that memory loss may involve a gradual transition in amyloid proteins from functional and benign forms to more rigid and damaging ones. Rubén Hervás, a Spanish biochemist at the University of Hong Kong who led the study, said the process could explain part of the normal memory decline that occurs with ageing.
The researchers also point to a possible connection with humans. Orb2 has human counterparts, including CPEB3. Hervás said that, if similar structural changes occur in human CPEB3 and can be reversed by certain chaperones, future drugs might be able to preserve or restore forms of the protein associated with more efficient synaptic protein production and better memory.
A project funded by the Government of Hong Kong with one million euros will investigate whether the mechanism observed in fruit flies also occurs in humans. José Javier Lucas, a researcher at the Severo Ochoa Molecular Biology Center who was not involved in the study, said the work could help explain the molecular basis of memory loss that affects people as they age.
Lucas also highlighted the broader implications of the research. Amyloids may regulate physiological functions throughout the body, not only in the brain, raising the possibility that changes in their functionality could contribute to other age-related problems. Whether the same process occurs in humans remains to be established.
Sources: El País Ciencia.