Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection

Vatner, Stephen F.; Pachon, Ronald; Vatner, Dorothy E.

doi:10.1155/2015/250310

Cited by 31 publications

(32 citation statements)

References 142 publications

(112 reference statements)

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“…The liver is a central organ for the maintenance of lipid and glucose homeostasis and, due to this fact it is susceptible to oxidative stress damage [Qureshi and Abrams, ; Meng et al, ]. It is known that oxidative stress increases with aging [Vatner et al, ]. Thus, we hypothesize whether disturbances in the hepatic glucose homeostasis is related to the oxidative stress in old rats.…”

Section: Discussionmentioning

confidence: 88%

Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age‐Related Changes in the Hepatic Metabolism of Rats

Heck

Fulco

Quines

et al. 2016

J of Cellular Biochemistry

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Aging is characterized by a widespread loss of homeostasis in biological systems and is accompanied by pathophysiological changes including the liver injury. The aim of the present study was to investigate the effects of the combined therapy with swimming exercise (20 min session, 5 days/week during 4 weeks) and a diet supplemented with 1 ppm of (PhSe) on the hepatic metabolic alterations caused by aging in rats. In this study, male old Wistar rats had an increase in the epididymal fat relative weight, disturbances in the activities of hepatic enzymes associated to the glucose homeostasis, higher hepatic triglyceride content and higher activity of the plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The combined therapy normalized the activities of glucose-6-Pase and tyrosine aminotransferase, gluconeogenic enzymes, increased the hepatic glycogen content and was effective against the increase in the hepatic triglycerides content, without altering the activities of hexoquinase, and citrate synthase. Moreover, the combined therapy normalized the activities of AST and ALT, indicating a hepatoprotective effect. The combined therapy with swimming exercise and a diet supplemented with 1 ppm of (PhSe) contributed to the hepatic glucose homeostasis in old rats. Nevertheless, more studies are needed to investigate the possible mechanisms of action behind these effects. J. Cell. Biochem. 118: 1574-1582, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 88%

Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age‐Related Changes in the Hepatic Metabolism of Rats

Heck

Fulco

Quines

et al. 2016

J of Cellular Biochemistry

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“…AC5 is a major regulator of cardiac inotropy and chronotropy, however it could also have adverse effects for the heart. In fact, in mouse models, cardiac-specific overexpression of AC5 enhanced basal cardiac performance [ 139 ], but also decreased the cardiac resistance to prolonged stress [ 140 ]. The adverse effects of AC5 overexpression are attributed to a pathway that involves the SIRT1/FoxO3a axis [ 141 ].…”

Section: Key Playersmentioning

confidence: 99%

Compartmentalized Signaling in Aging and Neurodegeneration

Benedetto

Iannucci

Surdo

et al. 2021

Cells

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The cyclic AMP (cAMP) signalling cascade is necessary for cell homeostasis and plays important roles in many processes. This is particularly relevant during ageing and age-related diseases, where drastic changes, generally decreases, in cAMP levels have been associated with the progressive decline in overall cell function and, eventually, the loss of cellular integrity. The functional relevance of reduced cAMP is clearly supported by the finding that increases in cAMP levels can reverse some of the effects of ageing. Nevertheless, despite these observations, the molecular mechanisms underlying the dysregulation of cAMP signalling in ageing are not well understood. Compartmentalization is widely accepted as the modality through which cAMP achieves its functional specificity; therefore, it is important to understand whether and how this mechanism is affected during ageing and to define which is its contribution to this process. Several animal models demonstrate the importance of specific cAMP signalling components in ageing, however, how age-related changes in each of these elements affect the compartmentalization of the cAMP pathway is largely unknown. In this review, we explore the connection of single components of the cAMP signalling cascade to ageing and age-related diseases whilst elaborating the literature in the context of cAMP signalling compartmentalization.

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“…The rapid progress in the understanding of the human genome has opened up new avenues for studying interactions between nutrients and the genome [ 1 ]. Up to now, it has been clearly shown that one common mechanism that mediates cellular longevity and healthful aging is protection against oxidative stress [ 2 ]. Notably, an excessively high level of reactive oxygen species (ROS) with normal levels of endogenous antioxidant enzymes is the basis for oxidative stress in the brain, which causes apoptosis and cell damage.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Hydrogen Peroxide‐Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone‐Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes

Ismail

Azmi

et al. 2015

Oxidative Medicine and Cellular Longevity

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Nigella sativa Linn. (N. sativa) and its bioactive constituent Thymoquinone (TQ) have demonstrated numerous pharmacological attributes. In the present study, the neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated. TQRF was extracted using supercritical fluid extraction while TQ was acquired commercially, and their effects on H2O2 were evaluated using cell viability assay, reactive oxygen species (ROS) assay, morphological observation, and multiplex gene expression. Both TQRF and TQ protected the cells against H2O2 by preserving the mitochondrial metabolic enzymes, reducing intracellular ROS levels, preserving morphological architecture, and modulating the expression of genes related to antioxidants (SOD1, SOD2, and catalase) and signaling genes (p53, AKT1, ERK1/2, p38 MAPK, JNK, and NF-κβ). In conclusion, the enhanced efficacy of TQRF over TQ was likely due to the synergism of multiple constituents in TQRF. The efficacy of TQRF was better than that of TQ alone when equal concentrations of TQ in TQRF were compared. In addition, TQRF also showed comparable effects to TQ when the same concentrations were tested. These findings provide further support for the use of TQRF as an alternative to combat oxidative stress insults in neurodegenerative diseases.

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Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection

Cited by 31 publications

References 142 publications

Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age‐Related Changes in the Hepatic Metabolism of Rats

Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age‐Related Changes in the Hepatic Metabolism of Rats

Compartmentalized Signaling in Aging and Neurodegeneration

Modulation of Hydrogen Peroxide‐Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone‐Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes

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