The bottom line: A new mouse study suggests that the innate immune sensor STING may need to be controlled rather than completely switched off. Drug treatment improved several premature-aging features and extended survival in progeroid mice, while permanent genetic deletion produced more limited benefits. The work is mechanistic and preclinical.
Chronic activation of the cGAS-STING pathway has become a major candidate mechanism in inflammaging. The pathway normally detects DNA where it should not be and launches an immune response. With age, damage to the nuclear envelope can allow fragments of chromatin to appear in the cytoplasm, keeping that alarm active.
A study in Nature Communications describes a control system at the nuclear periphery. Lamin A/C, a structural protein encoded by LMNA, acted as a scaffold that brought STING together with the enzyme CK2alpha. CK2alpha phosphorylated STING and promoted its turnover, limiting its accumulation and downstream inflammatory signaling.
Related: A new study of mice without cGAS found that complete loss of the upstream sensor disrupted LINE1 control, increased inflammation and shortened median lifespan. Read Scientists Tried Removing an Inflammaging Trigger. The Mice Aged Faster.