The abstract is read at the publisher; the summary is JClub's.
In primary human fibroblasts, mitochondrial respiratory chain inhibition creates NADH-reductive stress alongside profound NADPH depletion, and NADH/NAD+ normalization alone does not rescue proliferation arrest.
- Why it matters: NADH-reductive stress is linked to mitochondrial dysfunction and ageing, but the specific NAD(P)H redox coupling that produces metabolic vulnerabilities and limits recovery is unclear.
- What they did: The study used EcSTH in cells with intact mitochondria to perturb NAD(H) and NADP(H), then applied metabolomics, transcriptomics, and stable isotope tracing; it also tested SaNADK to expand NADP(H).
- The result: SaNADK restored reductive carboxylation and de novo pyrimidine biosynthesis in fibroblasts, reversing proliferation arrest and senescence features, and hepatic SaNADK expression in aged male mice partially alleviated inflammation and metabolic dysregulation signatures.
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.