Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation.

ABSTRACT: Werner syndrome (WS), caused by mutations in the RecQ helicase WERNER (WRN) gene, is a classical accelerated aging disease with patients suffering from several metabolic dysfunctions without a cure. While, as we previously reported, depleted NAD⁺ causes accumulation of damaged mitochondria, leading to compromised metabolism, how mitochondrial NAD⁺ changes in WS and the impact on WS pathologies were unknown. We show that loss of WRN increases senescence in mesenchymal stem cells (MSCs) likely related to dysregulation of metabolic and aging pathways. In line with this, NAD⁺ augmentation, via supplementation with nicotinamide riboside, reduces senescence and improves mitochondrial metabolic profiles in MSCs with WRN knockout (WRN^-/-

SUBMITTER: Lautrup S 

PROVIDER: S-EPMC12074813 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature