A novel information-theoretic approach reveals loss of effective biomolecular communication in aging muscle cells

Maintenance of organismal function requires tightly regulated biomolecular communication. However, with aging, communication deteriorates, thereby disrupting effective information flow. Using information theory applied to skeletal muscle single-cell RNA-seq data from young, middle-aged, and aged animals, we quantified the loss of communication efficiency over time. We considered communication channels between transcription factors (TFs; "input message") and corresponding target genes (TGs; "output message"). Mutual information (MI), defined as the information effectively transmitted between TFs and TGs, declined with age. This decline was attributed to escalating biological noise and loss of precision with which TFs regulate TGs (ie, channel capacity). When we ranked TF:TG pairs by MI, pairs associated with fatty acid oxidation displayed the greatest loss of communication with aging, whereas the system preserved communication between pairs related to RNA synthesis. These data suggest ineffective communication with aging against a backdrop of resource reallocation to support essential cellular functions.