Amelioration of premature aging in Werner syndrome stem cells by targeting SHIP/AKT pathway.

ABSTRACT:

Background

Pathogenic or null mutations in WRN helicase is a cause of premature aging disease Werner syndrome (WS). WRN is known to protect somatic cells including adult stem cells from premature senescence. Loss of WRN in mesenchymal stem cells (MSCs) not only drives the cells to premature senescence but also significantly impairs the function of the stem cells in tissue repair or regeneration.

Results

In this study, we profiled the signaling pathways altered in WRN-deficient MSC and applied pharmacological method to activate the AKT signaling in these cells and examined their cellular phenotype related to aging. We found that the AKT signaling in WRN-deficient MSCs was significantly suppressed while the AKT upstream phosphatases (SHIP1/2) were upregulated. Knockdown or inh

SUBMITTER: Tam HY 

PROVIDER: S-EPMC11765919 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature