Computational modeling reveals declining transcriptional communication fidelity across aging mouse tissues, indicating that input mismatch drives regulatory failure.
Key Points
To establish an information-theoretic model to quantify regulatory communication fidelity between transcription factors and target genes, and evaluate how this fidelity changes during cellular aging.
Developed a conditional maximum entropy model treating regulatory networks as communication channels to estimate mutual information between transcription factors and their target genes.
Decomposed mutual information dynamics to isolate the separate contributions of communication channel integrity and transcription factor activity input distributions across aging mouse tissues.
Mutual information between transcription factors and target genes declined with age across mouse tissues, predominantly driven by input mismatch rather than channel corruption.
Aging coincided with network centralization and loss of stabilizing network motifs, while in silico upregulation of select transcription factors restored youthful information transfer and gene expression.