Transcriptional drift in aging cells: A global decontroller.

Abstract

As cells age, they undergo a remarkable global change: In transcriptional drift, hundreds of genes become overexpressed while hundreds of others become underexpressed. Using archetype modeling and Gene Ontology analysis on data from aging <i>Caenorhabditis elegans</i> worms, we find that the up-regulated genes code for sensory proteins upstream of stress responses and down-regulated genes are growth- and metabolism-related. We observe similar trends within human fibroblasts, suggesting that this process is conserved in higher organisms. We propose a simple mechanistic model for how such global coordination of multiprotein expression levels may be achieved by the binding of a single factor that concentrates with age in <i>C. elegans</i>. A key implication is that a cell's own responses are part of its aging process, so unlike wear-and-tear processes, intervention might be able to modulate these effects.