As in heart failure, exercise tolerance is markedly diminished and is actually an early diagnostic sign, which precedes the overt manifestation of the inherent cardiac defect at rest, the development of a new therapeutic modality based on the salutary effects of the AC5 KO would be significant, not only to maintain fitness, but could also to ameliorate diseases such as heart failure, diabetes, obesity, and other chronic illnesses, which limit healthful aging. The gene discussed is ADCY5; the disease is obesity due to melanocortin 4 receptor deficiency.