Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging.

ABSTRACT: Mitochondrial dysfunction is linked to age-associated inflammation or inflammaging, but underlying mechanisms are not understood. Analyses of 700 human blood transcriptomes revealed clear signs of age-associated low-grade inflammation. Among changes in mitochondrial components, we found that the expression of mitochondrial calcium uniporter (MCU) and its regulatory subunit MICU1, genes central to mitochondrial Ca²⁺ (mCa²⁺) signaling, correlated inversely with age. Indeed, mCa²⁺ uptake capacity of mouse macrophages decreased significantly with age. We show that in both human and mouse macrophages, reduced mCa²⁺ uptake amplifies cytosolic Ca²⁺ oscillations and potentiates downstream nuclear factor kappa B activation, which is central to

SUBMITTER: Seegren PV 

PROVIDER: S-EPMC10353943 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature