Evidences suggest that in healthy individuals SIRT6 suppresses IGF signaling–related genes by binding and silencing expression from AP1-dependent promoters, and this contributes to metabolic homeostasis and the maintenance of a healthy heart. Low expression of SIRT6 possibly caused by a high-fat diet, sedentary lifestyle and/or genetics results in reduced SIRT6 silencing, and overexpression of IGF and possibly also of other AP1-dependent genes, thus promoting cardiomyopathy, heart failure and early death.
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