Abstract
Background: The decline in organ function due to aging significantly impacts the health and quality of life of the elderly. Assessing and delaying aging has become a major societal concern. Previous studies have largely focused on differences between young and old, often overlooking the complexity and gradual nature of aging.
Methods: We annotated the aging trajectories of 16 organs to reveal functional specificity and identify organ-specific aging trend genes. Through inter-organ correlation analysis, we identified a set of global aging trend genes and constructed a multi-organ aging assessment (2A) model, which was validated using gene expression and pharmacogenomic data from mice and humans. Additionally, we used a random walk algorithm and GSEA enrichment analysis to screen for drugs that could improve multi-organ aging.
Results: The 2A model, constructed using aging trend genes, effectively evaluates the aging status in human and mouse tissues and predicts the clearance of senescent cells. The model scores exhibit a strong correlation with actual age, highlighting its robustness and reliability. Functional annotation indicated that the lungs and kidneys are particularly sensitive to aging, with immune function and cell death playing key roles. Notably, single-cell data confirmed that plasma cell accumulation and naive-like cell reduction showed linear changes during organ aging. The aging trend genes of each organ are significantly enriched with aging-related functions, allowing for precise assessment of the aging process and identification of specific aging milestones for each organ. In addition, drug screening pinpointed Fostamatinib, Ranolazine, and Metformin as influential in multi-organ aging. Enrichment analysis further elucidated their impact on critical aging-related pathways, including longevity regulation and circadian rhythm.
Conclusion: This study elucidated functional changes during organ aging and developed the 2A model as a robust method for monitoring aging. Additionally, our research provides a foundation for anti-aging drug screening and establishes a scientific framework for intervening in organ aging.