Interferon Regulatory Factor 7 inhibition reverts the age-induced mitochondrial alterations in mesenchymal stem cells

Abstract

Mitochondrial dysfunction and a low-grade-chronic inflammation are amongst the major hallmarks of aging, but the mechanisms underlying their etiology and causal connection with age remain largely unknown. We reveal herein an unprecedented, cell-autonomous role of Interferon Regulatory Factor 7 (IRF7) in leading mitochondrial alterations with age. Specifically, we show that increased interferon signaling and mitochondrial alterations are the prominent changes which occur in mesenchymal stem cells as they age. Integrated transcriptional analysis indicate IRF7 to be the major driver of these changes and the inhibition of IRF7 is sufficient to revert both, determining diminished interferon signaling and increased mitochondrial gene expression. In addition, IRF7 inhibition partially reverted age-associated alterations of mitochondrial structure and "metabolomics" profile. Our results reveal IRF7 as a major regulator of aging-related mitochondrial alterations and point it out as an ideal candidate for the development of effective therapies against aging and aging-related diseases