Effect of intracellular acidification on senescence-related transcriptomic changes

Several remodeling of intracellular environments has been identified in senescent cells, including enlargement of cell / nuclear size and intracellular acidification. Although these alterations of intracellular environments were reported to be involved in unique characteristics of senescent cells, the contribution of intracellular acidification to senescence-associated cellular phenotypes is poorly understood. Here, we identified that upregulation of TXNIP and its paralog ARRDC4 as a hallmark of intracellular acidification in addition to KGA-type GLS1. These genes were also upregulated in response to senescence-associated intracellular acidification. Neutralization of the intracellular acidic environment ameliorated not only senescence-related upregulation of TXNIP, ARRDC4, and KGA, but also inflammation-related genes, possibly through suppression of glycolysis. Taken toghether, our data implied that the contribution of intracellular pH to senescence-associated cellular features, such as SASP. To investigate the effect of intracellular acidification, we prepared nutlin3a-induced senescent cells and cultured them under normal or alkali environment. RNA-seq was performed to detect alkali-induced transcriptomic changes in senescent cells.