Role of Melatonin in Angiotensin and Aging

Abstract

The cellular utilization of oxygen leads to the generation of free radicals in organisms. The accumulation of these free radicals contributes significantly to aging and several age-related diseases. Angiotensin II can contribute to DNA damage through oxidative stress by activating the NAD(P)H oxidase pathway, which in turn results in the production of reactive oxygen species. This radical oxygen-containing molecule has been linked to aging and several age-related disorders, including renal damage. Considering the role of angiotensin in aging, melatonin might relieve angiotensin-II-induced stress by enhancing the mitochondrial calcium uptake 1 pathway, which is crucial in preventing the mitochondrial calcium overload that may trigger increased production of reactive oxygen species and oxidative stress. This review highlights the role and importance of melatonin together with angiotensin in aging and age-related diseases.

Chronic arsenite exposure induced skeletal muscle atrophy by disrupting angiotensin II‐melatonin axis in rats

“…MT could effectively antagonize the cytotoxic effect of arsenic and acted as a novel potent therapeutic candidate in arsenic toxicity 44 . More importantly, accumulating evidence suggested there is a mutual regulatory relationship between AngII and MT, forming a negative feedback loop, so termed AngII–MT axis 34,45 …”

“…44 More importantly, accumulating evidence suggested there is a mutual regulatory relationship between AngII and MT, forming a negative feedback loop, so termed AngII-MT axis. 34,45 In order to illustrate the influence of environmental arsenic exposure on endogenous MT secretion and the possible roles of AngII-MT axis in arsenic-induced skeletal muscle atrophy, we further examined the influence of arsenite on serum AngII and MT levels. To our surprise, we found the serum levels of AngII and MT were both elevated after 3 months of arsenite exposure, however, the ratio of AngII to MT did not change obviously compared with the control group (Figure 5).…”

Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases

“…Of interest, the activation of the NADPH oxidase pathway by angiotensin II significantly promotes DNA damage and accelerates both aging and the appearance of multiple age-related pathologies, especially cardiovascular disorders. In relation to this, it has been suggested that melatonin could alleviate oxidative stress induced by angiotensin II through the activation of the mitochondrial calcium uptake 1 pathway, which is crucial in the prevention of mitochondrial calcium overload that may trigger exacerbated generation of damaging ROS (Sehirli et al, 2021).…”

A Review of the Potential Effects of Melatonin in Compromised Mitochondrial Redox Activities in Elderly Patients With COVID-19

“…It upregulates the production of IL-8, which acts as a chemotactic and activating factor for neutrophils, endothelial cells, and macrophages. SARS-CoV-2 infection enhances the expression of AGII, which activates NOX through the AGII type 1 receptor, and in turn, triggers the production of ROS and subsequent damage ( 26 ). SARS-CoV-2 may recognize the CD147 receptor (a glycoprotein that can cause a cytokine storm in lung epithelial cells) on the surface of the host cell by binding the viral nucleocapsid protein to the CD147 ligand cyclophilin A ( 27 ).…”

“…Previous studies have shown that melatonin can retard the aging of the gastric mucosa by stimulating telomerase activity and effectively inhibiting lipid peroxidation and cell proliferation ( 226 ). Melatonin can also reduce oxidative damage induced by angiotensin by inhibiting the production of ROS and RNS, inflammatory cytokines, and advanced glycation end products and preventing telomere shortening ( 26 ) ( Figure 7 ).…”