Signals from mitochondria to the nucleus may cause DNA fragments in the cell fluid and inflammation during cell aging

Dysfunctional mitochondria may drive the formation of cytoplasmic chromatin fragments (CCFs), triggering a proinflammatory response in senescent cells.

• CCFs are linked to a complex inflammatory response known as the senescence-associated secretory phenotype (SASP).
• A retrograde signaling pathway involving reactive oxygen species (ROS) and the JNK protein is implicated in CCF formation.
• The JNK protein interacts with 53BP1, which regulates processes related to DNA damage and CCF development.
• Low-dose HDAC inhibitors may restore mitochondrial gene expression, improve mitochondrial function, and reduce CCFs and SASP in senescent cells.
• In mouse models, HDAC inhibitors appear to mitigate oxidative stress, CCF formation, and tissue damage associated with senescence.

Simplified