By using three liver-targeted AAV8-based gene therapies targeting longevity-associated genes (fibroblast growth factor 21, FGF21; α-klotho; and the soluble form of mouse transforming growth factor-β receptor 2, sTGFβR2), this research aimed to tackle the combined pathologies of four age-related diseases, obesity, type II diabetes, heart failure, and renal failure, with a single treatment strategy. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.