Ageing individuals suffer endothelial dysfunction as a result of the activation of inducible nitric oxide synthase (iNOS) rather than eNOS [92]; in ageing rats, impaired endothelium-dependent vasodilatation was associated with reduced eNOS and increased iNOS, oxidative stress was increased and endogenous antioxidants were downregulated, whereas CR restored endothelial function and reduced iNOS expression and oxidative stress [92]. Here, NOS3 is linked to endothelial dysfunction.