Figure 1. Derepression of IGF signaling–related genes and hypertrophic cardiomyopathy by SIRT6 deficiency.

Sundaresan et al.7 provide evidence to 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. Ac, acetylated H3K9.