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Nitric oxide and aging — does it determine how quickly we age?

Sources: 10 · Article: 11 331 characters

Nathan S. Bryan claims that the body's ability to produce nitric oxide declines with age by 10–12% per decade.

  • According to him, nitric oxide depletion precedes symptoms and is linked to the onset and progression of chronic age-related diseases.
  • Nitric oxide is said to help neutralize harmful oxygen radicals.
  • Inside cells, it is said to increase the efficiency of converting oxygen into energy.

What the authors write

Nathan S. Bryan

As we age, the body is said to lose its ability to produce nitric oxide, declining by 10–12% per decade.

„As we age we lose our ability to produce NO. In fact about 10-12% every ten years starting in our late teens and early 20s. If you are over 40, no doubt you need nitric oxide even if you don’t have any clinical symptoms. Loss of nitric oxide is the first event in the onset and progression of a number of age related chronic conditions.”As we age we lose our ability to produce NO. In fact about 10-12% every ten years starting in our late teens and early 20s. If you are over 40, no doubt you need nitric oxide even if you don’t have any clinical symptoms. Loss of nitric oxide is the first event in the onset and progression of a number of age related chronic conditions.
Nathan S. Bryan

Nitric oxide depletion is said to precede symptoms and be linked to the onset and progression of chronic age-related diseases.

„Loss of nitric oxide is the first event in the onset and progression of a number of age related chronic conditions. You could be deficient in NO for a couple of years before you develop any clinical signs of deficiency. The best insurance policy you can have is to start a safe and effective nitric oxide product before any major health conditions.”Loss of nitric oxide is the first event in the onset and progression of a number of age related chronic conditions. You could be deficient in NO for a couple of years before you develop any clinical signs of deficiency. The best insurance policy you can have is to start a safe and effective nitric oxide product before any major health conditions.
Nathan S. Bryan

Nitric oxide is said to help neutralize harmful oxygen radicals.

„This explains why and how nitric oxide is a potent antioxidant molecule because it neutralizes toxic damaging oxygen radicals. Some people argue since nitric oxide metabolites, including nitrotyrosine are always present in diseases, that it is causing the disease.”This explains why and how nitric oxide is a potent antioxidant molecule because it neutralizes toxic damaging oxygen radicals. Some people argue since nitric oxide metabolites, including nitrotyrosine are always present in diseases, that it is causing the disease.
Nathan S. Bryan

Inside the cell, nitric oxide is said to increase the efficiency of converting oxygen into energy.

„Nitric oxide inside the cell increases the efficiency of oxygen conversion to cellular energy. Without sufficient nitric oxide, this process creates a lot of “oxidative stress” and formation of toxic oxygen radicals. This inefficient oxygen metabolism can lead to chronic fatigue syndrome, low pH, low oxygen and fermentation inside the cell.”Nitric oxide inside the cell increases the efficiency of oxygen conversion to cellular energy. Without sufficient nitric oxide, this process creates a lot of “oxidative stress” and formation of toxic oxygen radicals. This inefficient oxygen metabolism can lead to chronic fatigue syndrome, low pH, low oxygen and fermentation inside the cell.
Nathan S. Bryan

Nitric oxide is a molecule naturally produced in the body and a free radical.

„Nitric oxide is a naturally produced molecule in the human body. It is a free radical, which means it has an unpaired electron in its outer molecular orbit. Nitric oxide likes to donate its unpaired electron to make it more stable. Some free radicals like oxygen radicals will steal electrons from nitric oxide and other molecules causing oxidation.”Nitric oxide is a naturally produced molecule in the human body. It is a free radical, which means it has an unpaired electron in its outer molecular orbit. Nitric oxide likes to donate its unpaired electron to make it more stable. Some free radicals like oxygen radicals will steal electrons from nitric oxide and other molecules causing oxidation.

Research from PubMed · Europe PMC

We selected 4 studies with the best, positive results. This is a selection, not a full review of all research.

Total number of studies on this topic in PubMed: 5 844.

In mice, inhibiting arginase improved the intestinal barrier, reduced endotoxemia, and delayed the appearance of signs of aging in peripheral tissues.

Aim of the study: Aging is considered a state of low grade inflammation, occurring in the absence of any overt infection often referred to as 'inflammaging'. Maintaining intestinal homeostasis may be a target to extend a healthier status in older adults.

Results: In addition, employing multiple mouse models, we also show that while intestinal microbiota composition changes significantly during aging, fecal microbiota transplantation to old mice does not protect against aging-associated intestinal barrier dysfunction in small intestine. Rather, intestinal NO homeostasis and arginine metabolism mediated through arginase and NO synthesis is altered in small intestine of aging mice. Treatment with the arginase inhibitor norNOHA prevented aging-associated intestinal barrier dysfunction, low grade endotoxemia and delayed the onset of senescence in peripheral tissue e.g., liver. Intestinal arginine and NO metabolisms could be a target in the prevention of aging-associated intestinal barrier dysfunction and subsequently decline and 'inflammaging'.

Money for the studycompany together with others · Deutsche Forschungsgemeinschaft, Austrian Science Fund FWF, Europäische Kommission
Do the authors have ties to companies?no — the authors say so
Did a manufacturer help with the study?NO
Type of studyanimal study

“Not stated” does not mean nobody paid — the database does not always record it.

In mouse oocytes, exposure to nitric oxide delayed certain signs of aging and improved the integrity of the spindle apparatus.

Aim of the study: Nitric oxide (NO) is a ubiquitous signaling molecule that plays a crucial role in oocyte maturation and embryo development. However, its role in oocyte aging is unclear.

Results: Furthermore, NO exposure decreased the rate of spindle abnormalities in oocytes compared to unexposed controls. Interestingly, in old oocytes, the positive influence of NO was attenuated beyond 0.23 microM/min and disappeared at 0.46 microM/min NO. Overall, a significant dose-response relationship was noted between NO exposure and markers of aging with between 50 and 100 microM SNAP (0.11-0.23 microM/min NO, P < 0.0001). Collectively, our results demonstrate for the first time that exposure to NO delays oocyte aging and improves the integrity of the microtubular spindle apparatus in young and old oocytes.

Money for the studygovernment, public institutions · NHLBI NIH HHS
Do the authors have ties to companies?not stated
Did a manufacturer help with the study?unknown
Type of studyanimal study

“Not stated” does not mean nobody paid — the database does not always record it.

The review found that beetroot supplementation may briefly improve some measures of physical performance in older adults, but findings on blood pressure were inconsistent.

Aim of the study: The global population aged ≥65 years is increasing, posing challenges for healthcare systems and aging strategies. Beetroot extract (BE), derived from Beta vulgaris, is rich in inorganic nitrate (NO3-), nitrite (NO2-), betalains, and polyphenols, and has been proposed as an intervention to mitigate age-related physiological decline.

Results: However, robust cardiovascular benefits, particularly regarding blood pressure, cannot be firmly established because of heterogeneity in study designs, intervention durations, dosing protocols, participant characteristics, and small sample sizes. Furthermore, most trials have been conducted in younger or mixed-age cohorts, with limited evidence in older adults. Therefore, randomized controlled trials in aging populations are required to establish the clinical relevance of BE supplementation. The available evidence is preliminary and hypothesis-generating rather than sufficient to support BE as a strategy for healthy ageing.

Money for the studynot stated
Do the authors have ties to companies?not stated
Did a manufacturer help with the study?unknown
Type of studydiscussion of other studies

“Not stated” does not mean nobody paid — the database does not always record it.

In rats, walnut supplementation improved scores on a memory test, and serum reduced nitric oxide release in activated microglial cells.

Aim of the study: Aging is associated with increased neuroinflammation and a decrease in neuroplasticity, contributing to cognitive decline and increased risk for neurodegenerative disease. Nutritional interventions, such as walnut supplementation, may counteract these effects due to walnuts' high content of polyunsaturated fatty acids, polyphenols, and other bioactive compounds.

Results: Our results demonstrated that walnut supplementation improved performance by decreasing the number of errors made in the RAWM. Serum from walnut-fed rats significantly reduced NO release and iNOS expression in LPS-stimulated microglia. Hippocampal BDNF mRNA expression also differed according to age and diet, with higher expression in aged than young rats receiving the 9% walnut diet. These findings suggest that dietary walnuts may support healthy brain aging through effects on cognitive performance and circulating factors that modulate inflammatory responses and BDNF expression.

Money for the studynot stated
Do the authors have ties to companies?not stated
Did a manufacturer help with the study?unknown
Type of studyanimal study

“Not stated” does not mean nobody paid — the database does not always record it.

Perspectives and opinion materials

The content below presents the authors’ opinions, interpretations and hypotheses. It is not treated as equal to scientific studies and systematic reviews.

Orthomolecular Medicine News Service Opinion material
„(2023) Photobiomodulation and nitric oxide signaling. Nitric Oxide, 130:58-68. Gao X, Zhang W, Yang F, et al. (2021) Photobiomodulation Regulation as One Promising Therapeutic Approach for Myocardial Infarction. Oxid Med Cell Longev. 2021:9962922. Quirk BJ, Whelan HT (2020) What Lies at the Heart of Photobiomodulation: Light, Cytochrome C Oxidase, and Nitric Oxide-Review of the Evidence. Photobiomodul Photomed Laser Surg. 38:527-530. Ganipineni VDP, Gutlapalli SD, Ajay Sai Krishna Kumar I, et al.”(2023) Photobiomodulation and nitric oxide signaling. Nitric Oxide, 130:58-68. Gao X, Zhang W, Yang F, et al. (2021) Photobiomodulation Regulation as One Promising Therapeutic Approach for Myocardial Infarction. Oxid Med Cell Longev. 2021:9962922. Quirk BJ, Whelan HT (2020) What Lies at the Heart of Photobiomodulation: Light, Cytochrome C Oxidase, and Nitric Oxide-Review of the Evidence. Photobiomodul Photomed Laser Surg. 38:527-530. Ganipineni VDP, Gutlapalli SD, Ajay Sai Krishna Kumar I, et al.
Orthomolecular Medicine News Service Opinion material
„Niacin Increases Human Aortic Endothelial Sirt1 Activity and Nitric Oxide: Effect on Endothelial Function and Vascular Aging. Am J Transl Res 2023, 15, 6771-6778. Penberthy, W. Todd; Kristian B. Axelsen Table of NAD-Utilizing Enzymes 2022. Carlson, L.A. Nicotinic Acid: The Broad-Spectrum Lipid Drug. A 50th Anniversary Review. J Intern Med 2005, 258, 94-114, doi:10.1111/j.1365-2796.2005.01528.x.”Niacin Increases Human Aortic Endothelial Sirt1 Activity and Nitric Oxide: Effect on Endothelial Function and Vascular Aging. Am J Transl Res 2023, 15, 6771-6778. Penberthy, W. Todd; Kristian B. Axelsen Table of NAD-Utilizing Enzymes 2022. Carlson, L.A. Nicotinic Acid: The Broad-Spectrum Lipid Drug. A 50th Anniversary Review. J Intern Med 2005, 258, 94-114, doi:10.1111/j.1365-2796.2005.01528.x.
Orthomolecular Medicine News Service Opinion material
„This nutrient triage leads to cumulative oxidative and inflammatory injury, mitochondrial decay, and accelerated aging-manifesting clinically as cancer, ASCVD, diabetes, and neurodegeneration [19,76-78]. HDIVC directly reverses this triage imbalance: Repletion: It rapidly restores intracellular ascorbate far beyond dietary limits, replenishing a chronically triaged nutrient. Repair: It reactivates DNA demethylation (via TET enzymes), enhances collagen and carnitine synthesis, and normalizes nitric oxide signaling. Redox rebalance: It donates electrons to regenerate glutathione and vitamin E, reestablishing antioxidant buffering capacity.”This nutrient triage leads to cumulative oxidative and inflammatory injury, mitochondrial decay, and accelerated aging-manifesting clinically as cancer, ASCVD, diabetes, and neurodegeneration [19,76-78]. HDIVC directly reverses this triage imbalance: Repletion: It rapidly restores intracellular ascorbate far beyond dietary limits, replenishing a chronically triaged nutrient. Repair: It reactivates DNA demethylation (via TET enzymes), enhances collagen and carnitine synthesis, and normalizes nitric oxide signaling. Redox rebalance: It donates electrons to regenerate glutathione and vitamin E, reestablishing antioxidant buffering capacity.

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