Calorie restriction − which improves health and slows the aging process − has been reported to induce eNOS expression, improve mitochondrial biogenesis and increase Sirt-1 expression; thus, a positive feedback loop links Sirt-1 and eNOS [71], and activation of SIRT1 may help to reset the activity of eNOS during situations of endothelial dysfunction where NO availability is limited. The gene discussed is NOS3; the disease is endothelial dysfunction.