Transcriptional drift in aging cells: A global de-controller.

As cells age, they undergo a remarkable global change: In , hundreds of genes become overexpressed while hundreds of others become underexpressed. Using archetype modeling and Gene Ontology analysis on data from aging worms, we find that the upregulated genes code for sensory proteins upstream of stress responses and downregulated genes are growth- and metabolism-related. We propose a simple mechanistic model for how such global coordination of multi-protein expression levels may be achieved by the binding of a single ligand that concentrates with age. A key implication is that a cell's own responses are part of its aging process, so unlike for wear-and-tear processes, intervention might be able to modulate these effects.