Cited by 102Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionGenetics, Aging, and Longevity in Model Organisms

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An Overview of NO Signaling Pathways in Aging

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Pourbagher-Shahri, Ali Mohammad, Farkhondeh, Tahereh, Talebi, Marjan, Kopustinskiene, Dalia M., Samarghandian, Saeed, Bernatoniene, Jurga·2021·Molecules

DOI 10.3390/molecules26154533PMC PMC8348219

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Abstract

Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. Herein, we review the mechanisms of NO signaling in the cardiovascular system, central nervous system (CNS), reproduction system, as well as its effects on skin, kidneys, thyroid, muscles, and on the immune system during aging. The aging-related decline in NO levels and bioavailability is also discussed in this review. The decreased NO production by endothelial nitric oxide synthase (eNOS) was revealed in the aged cardiovascular system. In the CNS, the decline of the neuronal (n)NOS production of NO was related to the impairment of memory, sleep, and cognition. NO played an important role in the aging of oocytes and aged-induced erectile dysfunction. Aging downregulated NO signaling pathways in endothelial cells resulting in skin, kidney, thyroid, and muscle disorders. Putative therapeutic agents (natural/synthetic) affecting NO signaling mechanisms in the aging process are discussed in the present study. In summary, all of the studies reviewed demonstrate that NO plays a crucial role in the cellular aging processes.

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ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways
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Authors: Pourbagher-Shahri, A. M., Farkhondeh, T., Talebi, M., Kopustinskiene, D. M., Samarghandian, S., & Bernatoniene, J.
Affiliations: Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand 9717853577, Iran
Birjand University of Medical Sciences (IR)
Shahid Beheshti University (IR)
Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy, Lithuanian University of Health Sciences, Sukileliu Pr. 13, LT-50161 Kaunas, Lithuania
Neyshabur University of Medical Sciences (IR)
Corresponding author: Samarghandian, Saeed
ORCID: Pourbagher-Shahri, Ali Mohammad
Farkhondeh, Tahereh
Talebi, Marjan
Kopustinskiene, Dalia M.
Samarghandian, Saeed
Bernatoniene, Jurga
Venue: Molecules
Publisher: MDPI AG
Published: 2021-07-27
Volume: 26
Issue: 15
Pages: 4533
ISSN: 1420-3049 (ISSN-L)
DOI: 10.3390/molecules26154533
PMC: PMC8348219
OpenAlex: W3185759716
Cited by: 101
References: 307
Citations by year: 2026: 12 · 2025: 32 · 2024: 19 · 2023: 19 · 2022: 16 · 2021: 3
FWCI: 1.90
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Molecules (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Lithuanian University of Health Sciences (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: nitric oxide signaling, aging, endothelial nitric oxide synthase, neuronal nitric oxide synthase, cardiovascular aging, central nervous system aging, reproductive aging, erectile dysfunction, skin aging, kidney aging, muscle aging, immunosenescence, memory and cognition, therapeutic agents
MeSH terms: Aging, Animals, Cardiovascular System, Central Nervous System, Female, Genitalia, Humans, Male, Nitric Oxide, Signal Transduction, Down-Regulation, Cellular Senescence, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type III

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An Overview of NO Signaling Pathways in Aging

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