Abstract
Human diploid fibroblasts (HDFs) possess Ca(2+)-dependent membrane currents. These currents were suppressed in late-passage normal (senescent) HDFs and prematurely senescent HDFs derived from a subject with Werner syndrome (WS), compared with early-passage normal (young) HDFs. When young HDFs were microinjected with mRNA transcribed in vitro from a cDNA (WS3-10) which encodes a protein bearing a putative Ca(2+)-binding site and whose endogenous gene is overexpressed in senescent and WS HDFs, membrane currents fell to levels present in senescent and WS HDFs. Thus, both replicative senescence and forced expression of the WS3-10 gene sequence lead to suppression of Ca(2+)-dependent membrane currents, which suggests that a causal connection exists between these two processes.