articleNature CommunicationsJan 27, 2024GOLD OA

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging

JIJuan Ignacio Jiménez‐LoygorriBVBeatriz Villarejo‐ZoriÁVÁlvaro Viedma-PoyatosJZJuan Zapata‐MuñozRBRocío Benítez‐Fernández

Centro de Investigaciones Biológicas Margarita Salas · University of Fribourg · +2 more institutions

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Abstract

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological…

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Topics & keywords

Topics
Keywords
  • Mitophagy
  • Autophagy
  • Cell biology
  • Downregulation and upregulation
  • Mitochondrion
  • Inflammation
  • Cytosol
  • Sting
UN Sustainable Development Goals
  • Good health and well-being
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