YAP and TAZ in Cell Structure and Cell Senescence

This scientific commentary describes an interesting join the dots exercise in which scientists link together a number of different topics that have shown up over the years in research into aging. Here, the Hippo pathway (activated by YAP and TAZ), the shape and maintenance of the nuclear envelope, inflammatory cGAS/STING signaling, and cellular senescence are all connected. Declining expression of YAP and TAZ occur with aging, for reasons to be explored, and that decline appears sufficient in and of itself to trigger the rest of the linked cascade of changes and consequent cellular senescence and tissue dysfunction. A recent study tested the possibility that altered mechanosensing of the extracellular environment, i.e., the extracellular matrix (ECM), is a signal for physiological aging. The transcriptional coactivators and end effectors of the Hippo signaling pathway, YAP and TAZ, are established mediators that link mechanosensation to changes in cell behavior through the regulation of transcriptional programs. To explore the hypothesis that YAP/TAZ mediate effects of aging, the authors first performed a series of experiments employing single-cell RNA-seq data that indicated the downregulation of a YAP/TAZ activation signature gene set in dermal fibroblasts of old mice. This pattern of depressed YAP/TAZ activity was also observed in other stromal cells (e.g., kidney fibroblasts) as well as contractile cells (cardiomyocytes, vascular smooth muscle cells) but n...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs