Nitric Oxide as a Determinant of Human Longevity and Health Span

Abstract

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration.

Nitric Oxide as a Determinant of Human Longevity and Health Span

“…Food rich in L-arginine and antioxidants can exert potent anti-aging effects that increase health and fitness. Biomatrix precision supplementation uses nutrients that target the decisive metabolic pathways [40][41][42][43][44][45][46][47][48]. These are the arginine and tryptophan pathways, and they have to be rerouted [49][50][51][52][53][54][55][56][57][58][59][60].…”

“…Recent research has confirmed the decisive roles of these metabolic pathways in regulating and determining human health [40][41][42]. Exploring new avenues that enable active living and healthy aging by preserving our fitness throughout our entire lifetime is the ultimate aim and goal of ongoing research in the field [43][44][45][46][47][48]. The upregulation of NO bioavailability can prevent premature aging and neurodegeneration characterized by cognitive decline [49][50][51][52][53][54][55][56][57].…”

“…Supplementation with L-arginine and the B vitamins B 6 , folic acid, and B 12 can stop the vicious cycle [22,23]. Thus, tryptophan levels have to be selectively increased, for instance, by L-arginine or L-arginine-rich food that contains sufficient B vitamins, leading to enhanced formation of the antioxidant indole agents to boost NO bioactivity and bioavailability [22,23,[43][44][45][46][47]58,59]. Supplementation and dietary management of age-associated diseases target elevated blood pressure in the normal and high-normal range due to reduced endothelium-derived NO formation, reduced blood flow by improving endothelium-dependent NO-mediated vasodilation in the early stages of arteriosclerosis, and enhanced homocysteine levels by supplying sufficient folate, vitamin B 6 , and B 12 as needed [22,23,[43][44][45][46][47]58,59].…”

“…A biomatrix precision supplementation can provide all these nutrients that target the lower gastrointestinal tract with its resident symbiotic organisms to supply sufficient amounts of amino acids, antioxidants, and B vitamins [59]. This will restore an adequate supply of nitric oxide and increase tryptophan levels and synthesis of the protective antioxidant indole agents, melatonin, indole-3-propionic acid, and indole-3propionamide [43,45,59]. Current ongoing studies focus on approaches that utilize the potential of protective antioxidant scavenging and signaling by NO to significantly extend human life and health span [64].…”

“…Potent beneficial effects of L-arginine and B vitamins have been demonstrated to maintain or even improve human cardiometabolic and cardiovascular health [22,23,[61][62][63][64][65][66]. They exert antioxidant, anti-inflammatory, and antiaggregatory effects that can limit or even reverse premature aging and degenerative diseases [22,23,41,45,46,[59][60][61][62][63][64][65][66]. The supplementation of L-arginine and L-arginine-rich food with the B vitamins, vitamin B 6 , folic acid, and vitamin B 12 , allows for the successful dietary management of the age-dependent cardiometabolic diseases by assuring a sufficient supply of NO [20][21][22][23][24][61][62][63][64][65][66].…”