Loss of BCAP31 or POLR1E Accelerates Aging in C. elegans and Is Linked to Senescence in Vascular Endothelium

Building on our previous finding that the intracellular domain of CD44 (CD44ICD) is a critical aging regulator, we performed an interactome screen to identify its functional partners. This approach revealed BCAP31 and POLR1E as two previously unrecognized modulators of senescence.

Depletion of their respective orthologs in Caenorhabditis elegans (C. elegans) shortened lifespan and accelerated age-related functional decline. In human vascular endothelial cells, knockdown of BCAP31 or POLR1E induced premature cellular senescence, whereas their overexpression countered it. Importantly, the protein levels of both BCAP31 and POLR1E decreased during physiological aging across species, including in senescent endothelial cells, aged nematodes, and tissues from old mice, with BCAP31 reduction being particularly pronounced in the cardiovascular system.