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Elderly population and age-related diseases are on the rise. On the contrary, aging studies are technically hard to conduct, because they require elderly animals, the maintenance of which requires ample effort and is expensive. To tackle this problem, D-galactose is used to hasten the aging process in various tissues in rodent models and it has been shown to successfully mimic the oxidative alterations that take place in the natural aging process in various tissues both by our group and others. In the present study, the validity of D-galactose aging model in skeletal muscles was tested both on predominantly slow-twitch (soleus) and rather fast-twitch (gastrocnemius) muscle in male Sprague-Dawley rats and the results are compared with young littermate controls and naturally aged rats. Redox-related modifications in soleus and gastrocnemius were assessed by measurement of protein carbonyl groups, advanced oxidation protein products, lipid hydroperoxides, total thiol, and Cu, Zn-superoxide dismutase activities. In the present study, we provide biochemical evidence demonstrating that D-galactose-induced mimetic aging does result in oxidative stress-related redox alterations that are comparable with the alterations that occur in natural aging in soleus. On the contrary, in the D-galactose-induced mimetic aging of gastrocnemius, even though the oxidative stress markers were significantly increased, the endpoint redox homeostasis markers were not statistically comparable with the redox status of naturally aged group.

It is well known that in vitro storage lesions lead to membrane dysfunction and decreased number of functional erythrocytes. As erythrocytes get older, in storage media as well as in peripheral circulation, they undergo a variety of biochemical changes. In our study, the erythrocytes with different age groups in citrate phosphate dextrose adenine-formula 1 (CPDA-1) storage solution were used in order to investigate the possible effect of gender factor on oxidative damage. Oxidative damage biomarkers in erythrocyte membranes such as ferric reducing antioxidant power, pro-oxidant-antioxidant balance, protein-bound advance glycation end products, and sialic acid were analyzed. Current study reveals that change in membrane redox status during blood-bank storage condition also depends on both gender depended homeostatic factors and the presence of CPDA-1. During the storage period in CPDA-1, erythrocytes from the male donors are mostly affected by free radical-mediated oxidative stress but erythrocytes obtained from females are severely affected by glyoxidative stress.

Background: Testosterone biosynthesis gradually decreases with age. Impaired redox homeostasis-related oxidative damage in cellular macromolecules has a high risk for the development of renal insufficiency. Our aim was to study the effects of testosterone replacement therapy on redox homeostasis., Methods: We investigated various oxidative damage biomarkers in kidney. Experimental animals were separated into three groups-naturally aged rats, testosterone-administered naturally aged rats (single dose of 25 mg/kg testosterone enanthate), and their respective young controls., Results: Our results showed that the testosterone-administered naturally aged group shared significant similarities with the young rats with respect to their redox status. In testosterone-administered naturally aged rats, kynurenine, protein carbonyl, advanced oxidation protein products, lipid peroxidation markers, and xanthine oxidase activities were significantly lower and Cu-Zn superoxide dismutase activities and testosterone levels were higher than naturally aged rats. In testosterone-administered naturally aged rats, catalase activities, ferric reducing anti-oxidant power, and testosterone levels were significantly lower and dityrosine, N-formyl kynurenine, protein carbonyl, and protein hydroperoxides were significantly higher than in young rats. On the other hand, in naturally aged rats, Cu-Zn superoxide dismutase, catalase activities, ferric reducing anti-oxidant power, and testosterone levels were lower and dityrosine, kynurenine, protein carbonyl, protein hydroperoxide, advanced oxidation protein products, lipid peroxidation markers, advanced glycation end products, and xanthine oxidase activities were higher than controls., Conclusions: Our results showed that a single dose of testosterone administration has a positive effect on the redox status of the aged kidney. Future studies are needed to clarify the exact molecular mechanism(s) involved in the action of testosterone in maintaining kidney redox homeostasis.

Background: Increased systemic oxidative stress is considered as an important risk factor for prostate cancer occurrence; however, the relationship between impaired redox homeostasis of prostate tissue and aging remains unclear., Objective: In our study, we hypothesized that age-related deterioration of redox homeostasis in prostate tissue may be considered as a predisposing factor for prostate cancer occurrence., Methods: Sprague-Dawley rats were divided into two groups as young control (5 months) and naturally aged (24 months). We investigated the levels of oxidant and antioxidant parameters in prostate tissue., Results: Advanced oxidation protein products, protein carbonyl, non-protein thiol and lipid hydroperoxides levels of aged rats were significantly higher than in the young control rats (p < 0.01, p < 0.05, p < 0.001, p < 0.05, respectively). Additionally, antioxidant activity of Cu-Zn-superoxide dismutase in elderly group was significantly lower than young controls (p < 0.05)., Conclusions: We suggest that increased non-protein thiol levels found in aged rats may prevent further dissemination of oxidative protein damage. We also propose that the increased levels of oxidative protein damage markers and decreased Cu-Zn superoxide dismutase activity in aged prostate may be considered as a predisposing factor for prostate cancer. Further studies are warranted to clarify all these oxidative changes as initiation factors for prostate cancer in the association of aging with prostate cancer.

Background: The effect of the natural aging process on systemic redox homeostasis is previously documented. However, none of the studies specify the effect of experimental aging on systemic redox homeostasis. The purpose of this study is to clarify the ambiguity raised in preliminary reports as to mimetic aging dependency of the type and magnitude of oxidative damage on constituents of plasma., Methods: In the current study, we investigated the interrelationship among various groups of the systemic oxidative damage markers such as protein oxidation products (protein carbonyl groups, protein hydroperoxides, advanced oxidation protein products, protein thiol groups), lipid peroxidation products (malondialdehyde, lipid hydroperoxides, conjugated dienes), glycoxidation adducts (advanced glycation end products), and antioxidant capacity (ferric reducing/antioxidant power, Cu,Zn-superoxide dismutase, total thiol, non-protein thiol). All these markers were measured in plasma of mimetically aged (MA) rats (5-month-old rats subjected to d-galactose-induced experimental aging), naturally aged (NA) rats (24-month-old), and their corresponding young controls (YC) (5months old)., Results and Conclusions: Our current results show that systemic oxidation markers of the MA group share significant similarities in terms of impaired redox homeostasis with the NA rats and may be considered as a reliable experimental aging model for intravascular aging. Additional methodological studies including d-galactose dosage and application time are warranted to clarify the potential involvement of all these systemic redox variations as mechanistic factors in the development of mimetic aging related intravascular deterioration. Reversing or preventing systemic oxidative damage in experimental and natural aging should therefore be considered the primary target for the development of effective therapeutic strategies to prevent or treat age-related vascular disorders., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Age-related myocardial dysfunction has important implications with impaired redox homeostasis. Current study focused on investigation of redox homeostasis and histopathological changes in the myocardium of mimetically (MA), naturally aged (NA), and young control (YC) rats. Chronic D-galactose administration to young male Wistar rats (5 months old) was used to set up experimental aging models. We investigated 16 different oxidative damage biomarkers which have evaluated redox homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a protein oxidation biomarker, advanced oxidation end products, protein carbonyl groups, protein-bound advanced glycation end products, dityrosine, kynurenine, and N-formylkynurenine concentrations in MA and NA rats were found to be significantly higher compared to those in YC rats. On the other hand, the levels of protein thiol groups were not significantly different between groups, whereas lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and malondialdehyde in MA and NA rats were found to be significantly higher in comparison to those in YCs. For the assessment of oxidative DNA damage, we analyzed eight hydroxy-5'-deoxyguanosine concentrations of MA and NA groups which were higher than YCs. As an antioxidant status in the MA and NA groups, Cu-Zn superoxide dismutase, ferric reducing antioxidant power, and total thiol levels were lower than those in the YCs. Only nonprotein thiol levels were not significantly different. We also observed similar histopathological changes in MA and NA rats. We concluded that the mimetic aging model could be considered as a reliable experimental model for myocardial senescence.

A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not been fully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original research focuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic aging rats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establish mimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonyl groups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialic acid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides) and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young control groups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA (Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our results demonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose- induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, which are pertinent to increased oxidative stress and altered redox homeostasis.

Ageing of kidneys is a clinical health issue of the society. Age-related renal insufficiency has important implications due to impaired redox homeostasis. We examined protein, DNA and lipid oxidation biomarkers as well as protein-bound sialic acid (SA) in the kidney tissues of D-galactose induced ageing rats, naturally aged rats and their corresponding young control group. Intraperitoneal injection of D-galactose (60 mg/kg/day) for 6 weeks to young male Sprague-Dawley rats (20-week-old) was used to establish mimetic ageing model. In this study, we investigated the levels of protein carbonyl groups (PCO), various thiol fractions such as total thiol groups (T-SH), protein (P-SH) and non-protein thiol groups (NP-SH), lipid oxidation parameters such as lipid hydroperoxides (LHP) and malondialdehyde (MDA), SA and 8-hydroxy-2'deoxyguanosine (8-OHdG) parameters for comparison of naturally aged, induced aged and young rats. In D-galactose induced aged group, PCO, LHP, MDA, and 8-OHdG concentrations were significantly higher than young control group, whereas T-SH, P-SH levels were significantly lower than the young rats. In addition, NP-SH and SA concentrations were similar between the mimetic ageing and young control groups. In naturally ageing rats, PCO and MDA levels were significantly higher, whereas T-SH, P-SH, NP-SH concentrations were low compared to young controls. On the other hand, SA and 8-OHdG levels were not different between the naturally ageing group and the young control group. Our results demonstrated that the rats in the mimetic ageing group, have significant similarities with the naturally aged rats in terms of impaired redox homeostasis and can be used as a reliable animal model for renal ageing.

It has been reported that d-galactose administration causes an increase in oxidative and osmotic stresses in several tissues of rodents. In this study, we established a brain ageing model by using d-galactose and investigated the concentrations of oxidative stress markers on the hippocampus, parietal and frontal lobes of male Sprague-Dawley rats. A mimetic ageing model was established by injecting d-galactose (60 mg/kg/day/i.p.) in the experimental group for 42 days. At the end of this period, we tested spatial memory using the Morris water maze test. To investigate the magnitude of oxidative damage in proteins, lipids and DNA, we studied the concentrations of various oxidative stress parameters in the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell oxidative damage was observed in each of the three anatomic regions. It was found that protein carbonyl groups and advanced oxidation product concentrations in the d-galactose applied group were significantly high in each of the three brain lobes compared with the control group. Thiol concentration was found to be decreased in the parietal lobe. A concurrent increase in lipid hydroperoxides was also observed in this lobe. On the other hand, 8-hydroxy-2'-deoxyguanosine concentration was significantly increased in the hippocampal lobe of rats in the experimental group when compared with the controls. The results obtained from the mimetic ageing model rats showed that various anatomical regions of brain have different susceptibility to oxidative damage of proteins, lipids and DNA., (© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.)

A shift from redox regulation to oxidative damage is known to contribute organ dysfunction and aging-related disorders. Exposure to reactive oxygen species throughout the life-span increases the incidence of several liver diseases. A redox basis of the loss of antioxidant capacity of aged livers has not been fully elucidated in both genders. In the current study, we investigated the gender-dependent relations between protein carbonyl (PCO), a commonly used marker of protein oxidation and other protein oxidation parameters such as advanced oxidation protein products (AOPP) and total thiol (T-SH). Our study also covered other oxidative stress markers, such as malondialdehyde (MDA), lipid hydroperoxides (LHP), and glutathione (GSH) in liver tissue of the male and female aged rats. PCO and AOPP levels in old male and female rats were significantly higher than those in the young control groups (P < 0.001 and P < 0.01, respectively for male rats; P < 0.001 for both parameters in female rats). On the other hand, T-SH levels were not found to be different between young and old rat groups. Plasma MDA levels of old male and female rats were significantly higher compared to those of the young control groups (P < 0.01 and P < 0.001, respectively). LHP levels were only found out to be significantly higher in old female rats when compared to those in young male rats. GSH levels in old male and female rats were significantly lower than in the corresponding young control groups (P < 0.01 for male rats; P < 0.05 for female rats). Our results demonstrated greater susceptibility to hepatic oxidative damage in females than in males. This appears to contradict the general assumption that females are less susceptible to oxidative injury than males are.