Extended Data Fig. 10: Schematic illustration of nuclear egress and its regulation by glucose and metformin. | Nature Aging

Extended Data Fig. 10: Schematic illustration of nuclear egress and its regulation by glucose and metformin.

From: Metformin inhibits nuclear egress of chromatin fragments in senescence and aging

Extended Data Fig. 10: Schematic illustration of nuclear egress and its regulation by glucose and metformin.

During senescence and aging, chromatin fragments can be produced in the nucleus and shuttled to the cytoplasm via nuclear egress, mediated by ESCRT-III (including ALIX) and Torsin proteins. CCF in the cytoplasm activates the cGAS-STING pathway, driving chronic inflammation. Low glucose level or metformin activates AMPK, which phosphorylates ALIX, promoting ALIX binding to the autophagy adaptor LC3 and ALIX autophagic degradation. The loss of ALIX impairs nuclear egress of CCF, thereby inhibiting cGAS-STING activation and inflammation.

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