FIG. 3.

SIRT1 and SIRT6 in vascular aging. Aging processes, by blocking all cellular signals controlled by SIRT1 and SIRT6 (circle enclosed), lead to vascular aging. SIRT1 and SIRT6 deacetylate their specific and common substrates, including histone and nonhistone molecules, thus improving genome stability and preventing cell senescence. SIRT1 regulates eNOS via transcriptional and post-transcriptional deacetylation, resulting in the NO-mediated vascular protection. SIRT1 and SIRT6 control inflammation by deacetylating the p65 subunit of NF-κB, thus inhibiting the expression of inflammation-related genes, including ICAM-1, as well as proinflammatory cytokines. In ECs, SIRT6 protects from senescence and oxidative stress by blocking p21^Cip1/Waf1 signaling and sustaining high eNOS levels. The crosstalk between sirtuins and senescence-related proteins, such as p66^Shc, prevents vascular diseases based on antioxidative stress responses. →, positive regulation; ˧, negative regulation. ECs, endothelial cells; ICAM-1, intercellular adhesion molecule-1.