Tier 3 — preclinical

Nitric Oxide Signaling and Sensing in Age-Related Diseases

Mazuryk O, Gurgul I, Oszajca M, Polaczek J, Kieca K, Bieszczad-Żak E, Martyka T, Stochel G
Antioxidants (Basel) 2024 13(10):1213

Bibliography

PubMed
PMID 39456466
PubMed Central
PMC11504650
DOI
10.3390/antiox13101213
Funding
Supported by a grant from the National Science Centre, Poland (grant no. 2019/35/B/ST4/04266).
Competing interests
The authors declare no conflicts of interest.

Study snapshot

DesignNarrative literature review (not a primary study)
ModelN/A - review of cardiovascular, nervous, and immune system aging models
SampleN/A - review (280 references)
InterventionN/A - review
DurationN/A - review
EndpointsNO bioavailability and signaling pathway activity; S-nitrosation and nitration of disease-relevant proteins; NO sensing/detection method performance (sensitivity, selectivity)

What the study showed, in plain terms

Nitric oxide (NO) is a small gaseous signaling molecule that helps regulate blood vessel tone, nerve communication, and immune defenses throughout life. This review pulls together current research on how NO signaling changes as we age, and how those changes contribute to cardiovascular disease, neurodegeneration, and cancer.

As cells age, they tend to produce less NO and become less able to remove chemically-modified ("nitrosated" or "nitrated") proteins that accumulate from years of NO-related chemistry. The authors describe how this shift disrupts normal cell signaling in blood vessels, the brain, and immune cells, and survey emerging strategies - NO-releasing drugs, NO synthase inhibitors, and better diagnostic sensors for detecting NO in the body - that could help correct this imbalance and treat age-related disease.

Key findings

  • NO signaling relies heavily on post-translational protein modifications - S-nitrosation (of cysteine thiols) and tyrosine nitration - and both accumulate with age, disrupting protein function in mitochondria, sirtuins (SIRT1), and neuronal signaling proteins
  • In mitochondria, NO and peroxynitrite nitrate and S-nitrosate electron transport chain proteins (complexes I-IV) and regulators like Drp1, impairing energy metabolism and linking NO dysregulation to Parkinson's disease
  • NO plays a dual, context-dependent role in cancer, exerting both pro- and antitumorigenic effects depending on concentration, duration, and cellular source
  • New NO-sensing technologies - electrochemical sensors, fluorescent probes, photoacoustic imaging - are enabling earlier, non-invasive detection of NO dysregulation in cardiovascular, neurodegenerative, and cancer diagnostics

What this study can and cannot tell us

This is a narrative review, not a systematic review or meta-analysis, so it does not apply formal quality-appraisal criteria to the underlying studies it cites. Most of the mechanistic evidence discussed comes from cell and animal models rather than human clinical trials, and translating NO-modulating therapies to safe, targeted clinical use in aging populations remains an open challenge.

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Citation network

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Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability