“Zombie” Cells Reveal a Surprising New Driver of Chronic Inflammation

Key Points:

• Researchers have discovered a new mechanism by which dysfunctional mitochondria in senescent cells promote age-related inflammation by activating inflammatory genes through epigenetic modifications.
• Senescent cells release inflammatory molecules contributing to chronic inflammation linked to aging-related diseases, but instead of eliminating these cells, the study explores switching off their harmful inflammation.
• The study identifies two mitochondrial signals driving inflammation: leaked mitochondrial DNA/RNA triggering immune pathways and increased acetyl-CoA production enabling epigenetic changes that enhance inflammatory gene expression.
• Blocking the mitochondrial citrate transporter SLC25A1 reduces acetyl-CoA availability and limits inflammatory gene activation, suggesting a potential therapeutic target to reduce inflammation without destroying senescent cells.
• The findings, published in Nature by Mayo Clinic and Sanford Burnham Prebys Medical Discovery Institute researchers, provide a novel approach to promote healthier aging by modulating mitochondrial metabolism and epigenetic regulation of inflammation.