The association between IGF-1 levels and longevity in humans is very complex, and a recent meta-analysis shows that there is a U-shape nonlinear relationship with mortality; however, bioavailability of IGF-1 is affected by chronic inflammation and diet, and particularly proteins, dietary restrictions, obesity and lifestyle can modulate the level of IGF-1 to a physiological level [68]. Here, IGF1 is linked to obesity due to melanocortin 4 receptor deficiency.