MAM-STAT3-Driven Mitochondrial Ca⁺² Upregulation Contributes to Immunosenescence in Type A Mandibuloacral Dysplasia Patients.

ABSTRACT: Individuals with homozygous laminA/C p.R527C mutations manifest a severe form of Mandibuloacral dysplasia-(MAD) and exhibit overlapping progeroid symptoms, for which the underlying molecular pathology remains unknown. Herein, it is shown that MAD patients achieved inflammaging with different pro-inflammatory cytokines compared to progeria-(HGPS) patient. Characterization of MAD iPSC-derived Mesenchymal stem cells (MAD-iMSC) uncovers deregulated mitochondrial Ca⁺² as the primary cause of inflammaging, mediated through inflammasome formation rather than the cGAS-STING pathway. Moreover, MAD-iMSCs extracellular vesicles (EVs) can also upregulate mitochondrial Ca⁺² in healthy cells. This deregulated Ca⁺² homeostasis is indirectly mediated by mitochondrial calci

SUBMITTER: Padhiar AA 

PROVIDER: S-EPMC11791949 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature