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Published April 30, 2021 | Version v1
Journal article Open

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

Creators

  • 1. University of Verona 1 Department of Neuroscience, Biomedicine and Movement, Section of Anatomy and Histology , , 37134 Verona , Italy
  • 2. University of Trento 2 Department of Cellular, Computational and Integrative Biology , , 38123 Trento , Italy
  • 3. University of Piemonte Orientale 3 Department of Sciences and Technological Innovation , , 28100 Alessandria , Italy; University of Piemonte Orientale 4 Center for Translational Research on Autoimmune and Allergic Disease – CAAD , , 28100 Novara , Italy
  • 4. Polytechnic University of Marche 5 Department of Life and Environmental Sciences , , 20121 Ancona , Italy
  • 5. University of Pavia 6 Department of Public Health, Experimental and Forensic Medicine , , 27100 Pavia , Italy
  • 6. University of Brescia 7 Department of Biomedical Sciences and Biotechnology , , 25123 Brescia , Italy
  • 7. Stem Cell Research Laboratory 8 Department of Medicine, Section of Hematology , , , 37134 Verona , Italy; University of Verona 8 Department of Medicine, Section of Hematology , , , 37134 Verona , Italy

Description

ABSTRACT Dysregulated immunity and widespread metabolic dysfunctions are the most relevant hallmarks of the passing of time over the course of adult life, and their combination at midlife is strongly related to increased vulnerability to diseases; however, the causal connection between them remains largely unclear. By combining multi-omics and functional analyses of adipose-derived stromal cells established from young (1 month) and midlife (12 months) mice, we show that an increase in expression of interferon regulatory factor 7 (IRF7) during adult life drives major metabolic changes, which include 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.

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