Innovative Computational Platform Identifies Potential Compounds to Rejuvenate Aging Brain Cells

As our global population ages rapidly, age-related neurodegenerative diseases are becoming increasingly prevalent, posing significant health challenges worldwide. In response, a collaborative team of scientists from Spain and Luxembourg has developed a groundbreaking computational tool that could revolutionize how we approach brain aging. This innovative platform, detailed in the journal Advanced Science, employs a specialized brain-specific transcriptomic clock trained on gene expression data from healthy individuals aged 20 to 97. By applying machine learning techniques, the researchers identified 365 key genetic predictors of brain age, enabling precise estimates of biological age at the cellular level.

The research team used this clock to analyze gene expression data from various brain cell types, including neurons, to assess age-related changes. They found that patients with neurodegenerative conditions tend to have a higher biological age, supporting the idea that neurodegeneration can be viewed as accelerated aging of the brain. Importantly, the clock's predictions suggest that interventions capable of reducing this biological age could serve as neuroprotective strategies.

To find such potential rejuvenating agents, the scientists tested thousands of compounds on neural progenitor cells and neurons. They identified 453 substances that demonstrated significant rejuvenating effects, with some already known to extend lifespan or treat neurological disorders. These findings support the hypothesis that the predicted effects on biological age correlate with neuroprotection and health span extension.

Further validation involved testing three of these compounds in aged mice, where they observed notable improvements: reduced anxiety levels, enhanced spatial memory, and gene expression shifts toward a younger phenotype. These promising results highlight the computational clock's ability to identify candidate therapies for neurodegenerative diseases and pave the way for future research into brain rejuvenation.

Prof. Antonio Del Sol emphasizes that this platform not only identifies known therapeutic agents but also uncovers many novel candidates with rejuvenating potential. The study’s implications point towards a future where targeted molecular interventions could mitigate brain aging and neurodegeneration, ultimately improving quality of life and health outcomes for the aging population.