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As global populations age—with over 2 billion people projected to be over 60 by 2050—the race to combat neurodegenerative diseases intensifies. A breakthrough computational tool now offers a promising path: an AI-driven "aging clock" that not only measures brain cell biological age but systematically identifies compounds to reverse it.

Decoding Biological Age with 365 Genes

Researchers from CIC bioGUNE and the University of Luxembourg trained a machine learning model on gene expression data from 365 genes across healthy human brains (ages 20–97). Unlike chronological age, this clock measures biological age—revealing accelerated aging in neurodegenerative patients.

"Neurodegeneration manifests as accelerated aging. Our clock correlates predicted biological age with functional decline and disease severity," explains Dr. Guillem Santamaria, lead author of the study published in Advanced Science.

The Rejuvenation Screening Pipeline

The team applied the clock to screen 43,840 genetic and chemical perturbations, identifying 453 interventions predicted to reverse brain cell aging. Notably:
- 25% were known lifespan extenders (e.g., rapamycin analogues)
- 15% are currently used in neurological treatments
- 60% represent novel, unexplored compounds

"This isn't just validation—it's a discovery engine for entirely new neuroprotective pathways," emphasizes Prof. Antonio Del Sol, senior author.

From Silicon to Synapse: Mouse Model Validation

In collaboration with neuroscientists, three top compounds were tested in aged mice with striking results:
1. Reduced anxiety behaviors in maze tests
2. Enhanced spatial memory retention
3. Molecular rejuvenation: Cortical gene expression shifted toward younger profiles

The Therapeutic Horizon

While clinical applications require extensive validation, the platform enables systematic prioritization of high-potential interventions. Next steps include:
- Testing compound combinations for synergistic effects
- Validating efficacy in human neural organoids
- Assessing blood-brain barrier permeability

This convergence of computational biology and neuroscience marks a paradigm shift: instead of treating symptoms, we're now engineering tools to target aging itself—the root cause of neurodegeneration.

Source: CIC bioGUNE via Neuroscience News. Original research: Del Sol Mesa et al. (Advanced Science)