The fidelity of genetic information transfer with aging segregates according to biological processes

Abstract

AbstractMaintenance of cellular function requires highly coordinated communication between trillions of biomolecules. However, over time, communication deteriorates, thereby disrupting effective information flow and compromising cellular health. To quantify the age-related loss of molecular communication, we applied information theory to quantify communication efficiency between transcription factors (TF) and corresponding target genes (TGs). Using single cell RNA-seq data from the limb muscle of young, middle-aged, and aged mice, we found that the precision with which TFs regulate TGs diminished with age, but that information transfer was preferentially preserved in a subset of gene pairs associated with homeostasis—a phenomenon we termed “age-based canalization”. Collectively, these data suggest that aging may be accompanied by a reallocation of resources that favor messages crucial to maintenance of stability and survival.One sentence summaryAs communication efficiency in the regulatory network diminishes, aged cells prioritize homeostatic over adaptive functions.