The fidelity of genetic information transfer with aging skeletal muscle segregates according to biological processes https://www.biorxiv.org/content/10.1101/2022.07.18.500243v1
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 (TF; ‘input message’) and corresponding target genes (TG; ‘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 (i.e., channel capacity). When we ranked TF:TG pairs by MI, pairs associated with fatty acid oxidation displayed the greatest loss of communication with aging, while 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.
Figure 1: Useful information transmitted in transcriptional regulatory network declines with age as shown by decreasing mutual information.
Figure 2: Channel capacity with age declines with age.
Figure 3: TF:TG pairs can be segregated into a sub-set that display preserved information flow and channel capacity versus a sub-set in which information transfer is compromised.
Figure 4: Preserved and compromised genes displayed distinct enrichment to functional module.
Please check figshare to access the raw data. https://doi.org/10.6084/m9.figshare.20379720
Pre-processing steps for Smartseq2 data used here. https://github.com/czbiohub-sf/tabula-muris-senis/tree/master
Email me for any questions at sruthisivakumar.pitt@gmail.com