ArticleJournal of the American Heart Association2014
Aging of the nitric oxide system: are we as old as our NO?
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA.Current cardiology reviews · 2017Pooled it
- Effects of Fermented Garlic Extract Containing Nitric Oxide Metabolites on Blood Flow in Healthy Participants: A Randomized Controlled Trial.Nutrients · 2022Trial
- Effect of Vitamin C and Protein Supplementation on Plasma Nitrate and Nitrite Response following Consumption of Beetroot Juice.Nutrients · 2022Trial
- A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults.PloS one · 2020Trial
- Trial
- Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.Hormones & cancer · 2017Trial
- Asymmetric Dimethylarginine Limits the Efficacy of Simvastatin Activating Endothelial Nitric Oxide Synthase.Journal of the American Heart Association · 2016Trial
- Pathophysiology of Atherosclerotic Carotid Disease.Seminars in neurology · 2026Review
- Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations.International journal of molecular sciences · 2026Review
- Life-Course Regulation of Health and Disease by Nitric Oxide: Mechanistic Insights.Antioxidants (Basel, Switzerland) · 2026Review
- Iron, arginine, and redox metabolism in peripheral blood mononuclear cells distinguishes sickle cell disease and pulmonary hypertension.HemaSphere · 2026Article
- Microvascular Health as a Key Determinant of Organismal Aging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- NO-ergic mechanisms of age differences in photostimulation of lymphatic drainage, filtration, and clearance.Biomedical optics express · 2025Article
- Asymmetric Dimethylarginine: A Never-Aging Story.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2025Review
- Oxidative stress and regulation of adipogenic differentiation capacity by sirtuins in adipose stem cells derived from female patients of advancing age.Scientific reports · 2024Article
- Vascular Aging in Ischemic Stroke.Journal of the American Heart Association · 2024Review
- Sarcopenic obesity in older adults: a clinical overview.Nature reviews. Endocrinology · 2024Review
- Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.International journal of molecular sciences · 2024Article
- Inflammaging, immunosenescence, and cardiovascular aging: insights into long COVID implications.Frontiers in cardiovascular medicine · 2024Review
- Hallmarks of aging: middle-aging hypovascularity, tissue perfusion and nitric oxide perspective on healthspan.Frontiers in aging · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImpaired generation and signaling of nitric oxide (NO) contribute substantially to cardiovascular (CV) risk (CVR) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent CVR factor. Many processes involved in aging are modulated by NO. We therefore postulated that aging might be independently associated with impaired NO signaling. METHODS AND
resultsIn a prospective cohort study of 204 subjects (mean age 63±6 at study entry), we evaluated the effects of 4 years of aging on parameters of NO generation and effect, including platelet aggregability and responsiveness to NO, and plasma concentrations of the NO synthase inhibitor, asymmetric dimethylarginine (ADMA). Clinical history, lipid profile, high-sensitivity C-reactive protein, routine biochemistry, and 25-hydroxyvitamin D levels were obtained at study entry and after 4 years of follow-up. Aging was associated with marked deterioration of responsiveness of platelets to NO (P<0.0001) and increases in plasma ADMA concentrations (P<0.0001). There was a significant correlation between changes in these parameters over time (r=0.2; P=0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to NO were female gender (β=0.17; P=0.034) and low vitamin D concentrations (β=0.16; P=0.04), whereas increases in ADMA were associated with presence of diabetes (β=0.16; P=0.03) and impaired renal function (β=0.2; P=0.004).
conclusionsAging is associated with marked impairment of determinants of NO generation and effect, to an extent which is commensurate with adverse impact on CV outcomes. This deterioration represents a potential target for therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.