ADCY5 and obesity due to melanocortin 4 receptor deficiency: As the AC5 KO mice exhibit longevity and protection against diabetes, obesity, and cardiovascular disease (Yan et al., 2007, 2014; Lai et al., 2013; Ho et al., 2015) along with enhanced exercise performance demonstrated in the current investigation, this model replicates the human paradigm of healthful aging.