Structured Graphical Abstract.
The epigenetic regulator sirtuin 2 (SIRT2) governs a cytoplasm–mitochondria signal to repress vascular ageing. Ageing reduces SIRT2 protein levels and activity, which results in the hyperacetylation and activation of the adaptor protein p66Shc and production of mitochondrial reactive oxygen species (mROS), which subsequently reprogrammes the vascular transcriptome to aggravate ageing-induced vascular remodelling and diseases. The circulating SIRT2 may serve as a prognostic biomarker for ageing-related vascular diseases, and the cytoplasm–mitochondria axis SIRT2–p66Shc–mROS could be targeted for treating ageing-related vascular diseases.