An Overview of NO Signaling Pathways in Aging

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.

Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation

“…L-NG-nitroarginine methyl ester (L-NAME) treatment increases angiostatin via the inhibition of Cathepsin D, resulting in interstitial fibrosis [1]. In fact, the vascular dysfunction caused by endothelial dysfunction is one of the main vasculature alterations during cardiovascular ageing [2,3]. In addition, endothelial dysfunction, which is assessed by flow-medicated vasodilatation, is observed in CKD patients [4].…”

Anti-SARS-CoV-2 Action of Fluvoxamine may be Mediated by Endothelial Nitric Oxide Synthase

“…Further, the replication of SARS-CoV has been found to be inhibited by NO through two clearly different mechanisms: (i) Decrease in the palmitoylation of nascently-expressed spike (S) protein that impacts the fusion of the S protein with its cognate receptor, angiotensin converting enzyme 2; (ii) Decline in the production of viral RNA in the very first stages of viral replication, most likely attributed to the impact on one or both of the cysteine proteases that are encoded in open reading frame 1a (Orf1a) protein of SARS-CoV [6]. Later in the course of SARS-CoV infection, FLV-S1R-induced NO-increase may be cardio-, and renoprotective through lower oxidative stress, apoptosis, and systemic inflammatory responses, as previously demonstrated [7]. Patients with acute respirator y distress syndrome in a moderate-sized coronavirus disease 2019 (COVID-19) cohort showed lower soluble eNOS levels, implying that greater eNOS activity and the presumed increased NO synthesis probably prevent patients from serious lung complications [8].…”

Association between Glucose-6-Phosphate Dehydrogenase Deficiency and Asthma

“…It can be conjectured that the chronic depletion of NO, resulting from G6PD deficiency, may affect the basal bronchodilator tone sustained by this molecule [ 53 ]. More importantly, NO depletion manifests its effect, especially in the elderly, where there is a progressive impairment of antioxidant mechanisms [ 54 ]; perhaps this may partly explain why in our study, the magnitude of the association of G6PD deficiency with asthma was higher in patients after age 60 ( Figure 3 ).…”