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. 2012 Nov 15;9(1):26.
doi: 10.1186/1742-4933-9-26.

Endothelial nitric oxide synthase, vascular integrity and human exceptional longevity

Annibale Alessandro Puca  1 , Albino Carrizzo, Anna Ferrario, Francesco Villa, Carmine Vecchione
Affiliations

Endothelial nitric oxide synthase, vascular integrity and human exceptional longevity

Annibale Alessandro Puca et al. Immun Ageing. .

Abstract

Aging is the sum of the deleterious changes that occur as time goes by. It is the main risk factor for the development of cardiovascular disease, and aging of the vasculature is the event that most often impacts on the health of elderly people. The "free-radical theory of aging" was proposed to explain aging as a consequence of the accumulation of reactive oxygen species (ROS). However, recent findings contradict this theory, and it now seems that mechanisms mediating longevity act through induction of oxidative stress. In fact, calorie restriction - a powerful way of delaying aging - increases ROS accumulation due to stimulation of the basal metabolic rate; moreover, reports show that antioxidant therapy is detrimental to healthy aging. We also now know that genetic manipulation of the insulin-like-growth-factor-1/insulin signal (IIS) has a profound impact on the rate of aging and that the IIS is modulated by calorie restriction and physical exercise. The IIS regulates activation of nitric oxide synthase (eNOS), the activity of which is essential to improving lifespan through calorie restriction, as demonstrated by experiments on eNOS knockout mice. Indeed, eNOS has a key role in maintaining vascular integrity during aging by activating vasorelaxation and allowing migration and angiogenesis. In this review, we will overview current literature on these topics and we will try to convince the reader of the importance of vascular integrity and nitric oxide production in determining healthy aging.

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Figures

Figure 1
Figure 1
a) Representative nitric oxide pathway.b) Effects of aging on nitric oxide pathway. BH4 = tetrahydrobiopterin; Ca2+ = calcium ion; cGMP = cyclic guanosine monophosphate; eNOS = endothelial nitric oxide synthase; GTP = guanosine triphosphate; NADPH = nicotinamide adenine dinucleotide phosphate; NO = nitric oxide; ONOO- = Peroxynitrite; ADMA = Dimethylarginine; ROS = reactive oxygen species.
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