Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells

Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing time over the adult life and their combination at midlife is strongly related to increased vulnerability to diseases. However, their causal connection remains largely unclear. Combining multi-omics and functional analyses on adipose derived stromal cells established from young (1 month) and midlife (12 months) mice we show that the increase of Interferon Regulatory Factor 7 (IRF7) over the adult life drives major metabolic changes, which includes impaired mitochondrial function, altered amino acid biogenesis and reduced expression of genes involved in branched chain amino acid (BCAA) degradation. Our results draw a new paradigm of aging as the 'sterile' activation of a cell-autonomous pathway of self-defense and identify a crucial mediator of this pathway, IRF7, as driver of metabolic dysfunction with age.