SIRT1 and cardiac hypertrophy: Sirt1 deletion protects against pressure overload (PO)-induced cardiac hypertrophy (Oka et al., 2011; Sundaresan et al., 2011); however, low-level overexpression of SIRT1 in the heart attenuates age-associated cardiac hypertrophy, fibrosis, and cardiac dysfunction, while high-level overexpression of SIRT1 increases these pathological effects (Alcendor et al., 2007).