Sarm1-containing extrachromosomal circular DNA promotes aging-associated cardiac fibrosis via TGF-β/Smad activation - PubMed
4 hours ago
- #cardiac aging
- #eccDNA
- #TGF-β-Smad pathway
- Sarm1-containing extrachromosomal circular DNA (eccDNA) promotes aging-associated cardiac fibrosis via TGF-β/Smad activation.
- The number of eccDNAs is higher in aged cardiac tissues compared to young ones.
- Sarm1, located in eccDNAs, is identified as a key driver of cardiac aging through pro-fibrotic signaling.
- Knockdown of Sarm1 in aged mice improves cardiac function and reduces fibrosis.
- Overexpression of Sarm1 in young mice accelerates cardiac aging phenotypes.
- The TGF-β-Smad2/3 pathway is the dominant mechanism through which Sarm1 drives cardiac fibrosis.
- Pharmacological inhibition of Smad2/3 phosphorylation by SIS3 blocks Sarm1-driven effects.
- Targeting eccDNAs clearance and Sarm1 inhibition are proposed as novel therapeutic strategies for aging-related cardiac fibrosis.