Deciphering the Transcriptomic Signatures of Aging Across Organs in Mice

Aging, a major risk factor for numerous diseases, is associated with significant transcriptional changes across organs. However, the age of onset, extent of transcriptomic changes and how they unfold are not fully understood. We performed bulk RNA sequencing on eight organs (brain, heart, kidney, liver, lung, skeletal muscle, spleen, and testis) from male C57BL/6J mice across much of the murine lifespan covering 3-, 5-, 8-, 14-, 20- and 26-month-old animals. Our analysis revealed that age-related transcriptomic shifts vary in both timing and extent, with early shifts in lung, spleen, and testis; mid-life changes in heart, kidney, and skeletal muscle; and later alterations in brain and liver. The extent of age-related transcriptomic changes ranged from very low (testis) to high (kidney, liver, spleen). A linear mixed-effects model identified genes with tissue-specific aging trajectories. By integrating hub gene analysis and functional enrichment, we uncovered aging signatures that are either tissue-specific or shared across multiple organs, including those related to immune response, mitochondrial dysfunction, extracellular matrix remodeling, and cellular senescence. This study provides a systems-level resource for advancing aging research.