biostudies-literatureUnknownMatsuzaki TNIGMS NIH HHSAs cells age, they undergo a remarkable global change: In <i>transcriptional drift</i>, 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 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.bioRxiv : the preprint server for biology2023.11.21.568122https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690170biostudies-literatureTranscriptional drift in aging cells: A global de-controller.PMC10690170R35 GM122561Matsuzaki Tde Graff ADill KABalazsi GWeistuch CfalseTranscriptional drift in aging cells: A global de-controller.As cells age, they undergo a remarkable global change: In <i>transcriptional drift</i>, 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 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.2023-01-01T00:00:00Z2023 Nov2025-08-18T09:53:03.736Z2025-04-05T23:54:21.991ZS-EPMC106901703804534210.1101/2023.11.21.568122