SIRT1 and obesity due to melanocortin 4 receptor deficiency: In aged mice, the exogenous administration of MOTS-c improved physical performance and metabolic profiles, partly through its ability to increase NAD+ availability and modulate sirtuin pathways, including SIRT1 and SIRT3, both essential regulators of mitochondrial function and stress resistance [116], whilst recent studies have demonstrated that MOTS-c may also exert protective effects against diet-induced obesity and insulin resistance by altering skeletal muscle gene expression related to metabolism and inflammation [117].