Second, a combination gene therapy consisting of three longevity-associated AAV-delivered genes, namely fibroblast growth factor 21 (FGF21), αKlotho and a soluble form of mouse transforming growth factor-β receptor 2 (sTGFβR2) was shown to be beneficial on several mouse models of age-related diseases, such as obesity, type II diabetes, heart failure, and renal failure. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.