Gene expression-based drug repurposing to target aging

Area of Science:

• Gerontology and Pharmacology
• Neuroscience and Computational Biology

Background:

• Aging is the primary risk factor for numerous noncommunicable diseases.
• Genetic and chemical interventions in model organisms can extend lifespan and healthspan.
• Aging's complexity and interacting mechanisms challenge the discovery of anti-aging drugs.

Purpose of the Study:

• To discover drugs that combat aging in the human brain using a systems-level drug repurposing methodology.
• To identify pharmacological candidates by analyzing age-related gene expression changes in human brain tissue.
• To move beyond target-centric approaches by employing a data-driven, systems-level strategy.

Main Methods:

• Utilized multiple human brain gene expression datasets from individuals of varying ages.
• Identified gene expression patterns characteristic of aging.
• Compared aging-associated gene expression changes with drug-perturbed profiles in the Connectivity Map database.

Main Results:

• Identified 24 drugs significantly associated with age-related gene expression changes.
• Discovered drugs that may reverse detrimental aging effects or mimic cellular defense mechanisms.
• Validated the approach by finding known prolongevity drugs among the identified candidates, suggesting de novo drug discovery potential.

Conclusions:

• The systems-level drug repurposing approach effectively identifies potential anti-aging drugs for the human brain.
• This unbiased methodology, using human brain aging data, focuses on relevant biological processes.
• The findings open possibilities for discovering novel therapeutic targets for aging and age-related diseases.