Experimental limitations: Although our study provided a likely causal relationshipamong cardiac mechanical function, intracellular Ca2+homeostasis, NADPH oxidase, O2− accumulation,Akt/eNOS and stress signaling activation between aging and obesity, caution shouldbe taken for the interpretation of the precise interaction between aging and obesityin cardiac dysfunction in the human setting. This evidence concerns the gene FMO5 and obesity due to melanocortin 4 receptor deficiency.