Aging cartilage and osteoarthritis--what's the link?

Cartilage aging can contribute to the development of osteoarthritis (OA), the most common cause of chronic pain and disability in older adults. Articular cartilage is a unique tissue from the perspective of aging in that the cells (chondrocytes) and the majority of the extracellular matrix proteins experience little turnover, resulting in a tissue that must withstand years of use and can also accumulate years of aging-associated changes. Accumulation of advanced glycation end products (AGEs) occurs in cartilage, and the potential role of AGEs in the development of OA is being investigated. An age-associated reduction in growth factor signaling and an increase in oxidative stress may also play an important role in the age-OA connection. Further elucidation of mechanisms that affect chondrocyte function with aging should lead to novel interventions designed to slow the aging process in cartilage with the goal of preventing age-associated OA.     

Involvement of advanced glycation end products in the pathogenesis of diabetic complications: the protective role of regular physical activity

Advanced glycation end products (AGEs) may play an important role in the pathogenesis of chronic diabetic complications and in the natural process of biological aging. In fact, maintained hyperglycaemia favours the formation of AGEs at the tissue level in diabetic patients, which may influence the triggering of different chronic pathologies of diabetes such as retinopathy, nephropathy, neuropathy and macro- and micro-vascular diseases. Moreover, the literature has also demonstrated the involvement of AGEs in biological aging, which may explain the accelerated process of aging in diabetic patients. The practice of regular physical activity appears to positively influence glycaemic control, particularly in type 2 diabetes mellitus patients. This occurs through the diminution of fasting glycaemia, with a consequent reduction of glycation of plasmatic components suggested by the normalisation of HbA1c plasmatic levels. This exercise-induced positive effect is evident in the blood of diabetic patients and may also reach the endothelium and connective tissues of different organs, such as the kidneys and eyes, and systems, such as the cardiovascular and nervous systems, with a local reduction of AGEs production and further deceleration of organ dysfunction. The aim of this paper was to review the literature concerning this topic to coherently describe the harmful effects of AGEs in organ dysfunction induced by diabetes in advanced age as well as the mechanisms behind the apparent protection given by the practice of regular physical activity.     

Nitric oxide and oxidative stress in cardiovascular aging

The long-standing free radical theory of aging, which attributes cellular pathology to the relentless accumulation of reactive oxygen species (ROS), remains attractive but controversial. Emerging insights into the molecular interactions between ROS and reactive nitrogen species (RNS) such as nitric oxide suggest that, in biological systems, one effect of increased ROS is the disruption of protein S-nitrosylation, a ubiquitous posttranslational modification system. In this way, ROS may not only damage cells but also disrupt widespread signaling pathways. Here, we discuss this phenomenon in the context of the cardiovascular system and propose that ideas regarding oxidative stress and aging need to be reevaluated to take account of the balance between oxidative and nitrosative stress.     

Structure-(Dys)function relationships in mitochondrial electron transport chain complex II?

It has been postulated that mitochondrially derived reactive oxygen species (ROS) play a major causative role in aging processes. The primary sources of these oxidants are believed to be complexes I and III of the electron transport chain, with little evidence supporting oxidant formation at complex II (succinate dehydrogenase). Mutation of a complex II protein has, however, been shown to cause increased oxidative stress and decreased life expectancy in the Caenorhabditis elegans mutant mev-1. A recent study by Yankovskaya and colleagues, in which the structure of Escherichia coli succinate dehydrogenase was determined, provides an explanation for these observations. Furthermore, these results suggest possible mechanisms by which electron leakage might occur at this site in the aged organism.     

Oxidative stress increases continuously with BMI and age with unfavourable profiles in males

Oxidative stress is a risk factor for chronic diseases and was previously shown to be independently associated with obesity. The authors investigated the relationship between body mass index (BMI), age and oxidative stress on 2190 subjects undergoing a health care examination. Total antioxidant status (TAS), total peroxides (TOC) and autoantibodies against oxidized LDL (oLAb) were used as oxidative stress biomarkers in addition to serum lipoproteins, bilirubin and uric acid. Gender-specific differences were observed for age, BMI, serum concentrations of bilirubin, low-density lipoprotein (LDL), uric acid and TAS, all of which were higher in males (p < 0.001), while high-density lipoprotein (HDL), HDL/LDL ratio and TOC were higher in females (p < 0.001). Total cholesterol (p < 0.05) and LDL were increased (p < 0.05), while HDL was decreased (p < 0.05) in overweight and obese subjects. This was accompanied by increased uric acid and TAS concentrations. Lowest oLAb titers were detected in obese subjects. In extremely obese subjects, increased TOC and decreased TAS were observed in spite of high uric acid levels. These results demonstrate that oxidative stress increases with increasing BMI and age, as a sequel to an impaired antioxidant status, the consumption of oLAbs, an increase of peroxides and uric acid and a disadvantaged lipid profile.     

Oxidative mutagenesis, mismatch repair, and aging

A PubMed search for the term "oxidative stress" yields over 29,000 articles published on the subject over the past 10 years; more than 2000 of these articles also include the term "aging" in their title or abstract. Many theories of aging predict causal roles for oxidative stress in the myriad of pathological changes that occur as a function of age, including an increasing propensity to develop cancer. A possible link between aging and cancer is the induction and accumulation of somatic mutations caused by oxidative stress. This Review focuses on small mutational events that are induced by oxidative stress and the role of mismatch repair (MMR) in preventing their formation. It also discusses a possible inhibitory effect of oxidative stress on MMR. We speculate that a synergistic interaction between oxidative damage to DNA and reduced MMR levels will, in part, account for an accumulation of small mutational events, and hence cancer, with aging.     

Exploiting proteomics in the discovery of drugs that target mitochondrial oxidative damage

To understand how oxidative stress contributes to aging and age-related diseases and to better evaluate the therapeutic effect of antioxidant drugs, it would be highly desirable to have a comprehensive and detailed readout of the types of oxidative damage that occur to proteins at a global or proteome level. In this Perspective, I examine how proteomics, defined here as the science of examining all proteins in an organelle, cell, or tissue in the context of biological phenomena, can be used to provide molecular details of mitochondrial protein oxidative damage. Specifically, I discuss approaches that combine knowledge of the mitochondrial proteome with newer mass spectrometry-based techniques that are capable of identifying proteins and sites of oxidative modification in a high-throughput manner.     

Why females live longer than males: control of longevity by sex hormones

Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.     

Insulin resistance,oxidative stress markers and the blood antioxidant system in overweight elderly men

The purpose of the study was to examine in the blood of overweight men aged from 62 to 83 years, the relationships between age and insulin resistance, selected parameters of the oxidative stress, and the antioxidant defense system. The population studied was divided into two groups: the group ‘young-old’ consisted of men aged 62 to 74 years old, and the group ‘old-old’– of men aged between 75 and 83 years. The total antioxidative status (TAS) and concentrations of thiobarbituric acid reactive substances (TBARS) were measured in the blood plasma. In the serum samples, the levels of antibodies against oxidized LDL (oLAB), glucose, total cholesterol, HDL-cholesterol, triglycerides and insulin were measured. Homeostasis Model Assessment of Insulin Resistance (HOMA_IR) was calculated. Concentration of reduced glutathione (GSH) and glutathione peroxidase activity (GPx) were determined in the red blood cells hemolysate. The results of the study did not show significant differences between groups investigated with respect to concentrations of TBARS, TAS, GSH and GPx. However, significantly higher concentrations of glucose and antibodies against oxLDL (p < 0.05) were observed in the group of men over 74 years old in comparison to the group of ‘young-old’ men. It was indicated that the increased insulin resistance and hyperglycemia in elderly men are related to body mass and that they cause intensified oxidative modifications of LDL.     

Oxidative stress and antioxidant defense system in healthy,elderly men: relationship to physical activity

The aim of the present study was to compare selected markers of oxidative stress and the antioxidant system between groups of men aged 65 or more, differentiated by their level of physical activity. Thirty-one community-dwelling healthy, elderly men (mean age 73.4 ± 6.1 years) with a good nutritional status participated in the study. The Caltrac accelerometer was used to estimate energy expenditure related to physical activity. Subjects were divided into two groups according to the criteria proposed by Bauman: less active (< 1600 kcal/week) and more active (> 1600 kcal/week). In all the men, plasma total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS) concentrations and hydrogen peroxide (H₂O₂) levels were determined. The reduced glutathione (GSH) content and glutathione peroxidase (GPx) activity in hemolyzed red blood cells were also measured. There were no significant differences in TAS, H₂O₂ concentrations and the activity of GPx between less and more active men. In the group of more active subjects, plasma levels of GSH were higher, while TBARS concentrations were lower compared with the group of less active men (p < 0.05). Negative correlation between GSH and TBARS levels was observed (r = -0.71; p < 0.01), and GSH concentrations positively correlated with level of physical activity (r = 0.63; p < 0.05). The results indicate that habitual physical activity can favorably affect antioxidant potential and prevent lipid peroxidation in healthy, elderly men.     

Determination of oxidative stress levels and some antioxidant enzyme activities in prostate cancer

In this study, the antioxidant enzyme activities such as (SOD, GSH, and CAT) and malondialdehyde (MDA) level which is the end product of lipid peroxidation, were determined from the serum samples taken from patients diagnosed with prostate cancer Van Yuzuncu Y?l University Medical Faculty of Educational Research and Training Hospital and ?stanbul Bagcilar Education Research Hospital. The SOD, GSH, and CAT activity of patient groups was found significantly lower than the healthy control group in patients with prostate cancer (p?相似文献   

A 1,408 km bicycle tour with prostate cancer patients—results of a pilot study

Negative psychological and physical effects of prostate cancer and its medical treatment may persist many years after diagnosis. The influence of a long cycling tour on rehabilitative or health-related effects with prostate cancer patients has not yet been studied. In practice, physicians and therapists rarely recommend cycling to prostate cancer. In May 2010, eight prostate cancer patients rode their bikes for over 1,408 km from Cologne to Marseille within 5 weeks. Endurance test, blood examinations (prostate-specific antigen (PSA), total testosterone, interleukin-6, oxidative stress, and antioxidant capacity) and quality of life questionnaires were completed before and after the tour. All eight subjects reached Marseille. Significant improvements could be observed in physical performance and certain quality of life scores (p?=?0.008), as well as a reduction of total testosterone (p?=?0.19). PSA levels did not change. This pilot study suggests that long bicycle tours with prostate cancer patients are feasible. Due to the missing control group and the small sample size, the results of this pilot study are limited.     

Non-income effects of welfare receipt on early childhood cognitive scores

Child poverty in America has become an enduring part of the social landscape that many families must navigate. As prior research has established that income transfers can affect child outcomes, we focus our attention on the conditions under which these transfers occur. Using panel data from the Fragile Families and Child Wellbeing Study, we examine the non-income effects of TANF participation on children's early cognitive development using methods to address statistical concerns about endogeneity and selection. Our results indicate that participating in TANF is negatively associated with cognitive development. Furthermore, we are able to identify maternal stress as a viable causal pathway between TANF receipt and cognitive development, a result that we are unable to replicate with a falsification test involving the Earned Income Tax Credit (EITC). Our results suggest that the structure of cash transfers may have effects on early childhood outcomes.     

No association of serum PSA with vitamin D or total oxidant-antioxidant capacity in healthy men

Background and aim: Vitamin D deficiency and oxidative stress were suggested to be related to prostate cancer risk. We aimed to investigate the association of serum PSA concentration with vitamin D and total oxidant/antioxidant levels.

Materials and methods: A total of 95 healthy men were enrolled for the cross sectional study. Serum PSA, 25(OH)D, serum total oxidant status, and total antioxidant status were measured.

Results: Serum PSA was significantly negatively correlated with serum total oxidant status (r=??0.309, p?=?.003) but there was no significant correlation between PSA and 25(OH)D (p?=?.383) or total antioxidant levels (p?=?.233). After adjustment for age BMI and smoking status with multiple regression analysis, there was no significant association between serum PSA and total oxidant status.

Conclusion: We find no evidence for an association between PSA and vitamin D levels or serum total oxidant/antioxidant levels.     

Glycation stimulates amyloid formation

Amyloidosis comprises a group of systemic and localized diseases with varied clinical presentations. In these diseases, amyloid forms when proteins with a largely alpha-helical structure lose their original conformation and are converted into a predominantly beta-sheet form, thereby increasing their propensity to form highly insoluble and fibrillar aggregates. Most soluble amyloid precursor proteins have substantial beta-pleated sheet secondary structure, and extensive beta-pleated sheet structure occurs in all of the deposited fibrils. The aberrant deposition of proteins as cellular inclusions or plaques in the form of amyloid fibrils is a characteristic hallmark of all amyloid diseases (or amyloidoses) and of the so-called conformational diseases. Environmental and genetic factors are known to be involved, but the mechanism by which this process happens still is poorly understood. Here we report a new finding from the Dutch group of Gebbink and colleagues, which points to the posttranslational process of glycation as a key mechanism in the formation of amyloid. These researchers showed that glycation causes albumin, a globular protein with a largely alpha-helical structure, to adopt a beta-pleated sheet structure and the quaternary structural element known as the cross-beta conformation. These are features commonly shared by all amyloids. This research is the first to show glycation as a predisposing factor for amyloidosis.     

The Psychoneuroendocrinology of (Sexual) Aggression

Summary

The contours of the psychoneuroendocrinology of (sexual) aggression are becoming clearer. The sex difference in aggression originally directed attention to androgens, but the role of androgens has been difficult to substantiate. Rather novel is the insight that (sexual) aggression may be viewed as a maladaptive stress response. The stress response system is composed of psychological elements (the interpretation and labeling of threats), the neural system, that subserves this interpretation, and finally the endocrine system permitting the organism to react to threats with a physical response such as flight or fight, and as such is vital for our self-protection. Aggression may be viewed as an inappropriate and exaggerated response to a perceived threat. The stress system is largely tuned by early life experiences. Both psychological and biological elements can be identified in the stress response system, allowing both psychotherapeutic and pharmacological approaches to treatment.     

The Levels of Cortisol,Oxidative Stress,and DNA Damage in the Victims of Childhood Sexual Abuse: A Preliminary Study

In this study we aimed to investigate serum cortisol, oxidative stress, and DNA damage in children who are sexual abuse victims. The study included 38 children who sustained child sexual abuse and 38 age- and gender-matched children who did not have a history of trauma. Cortisol levels reflecting the status of the hypothalamic-pituitary-adrenal axis, anti-oxidant enzymes glutathione peroxidase, superoxide dismutase, natural anti-oxidant coenzyme Q, and 8-hydroxy-2-deoxyguanosine as the indicator of DNA damage were analyzed in serum samples using the enzyme linked immunosorbent assay method. Cortisol levels were significantly higher in the child sexual abuse group compared to the control group. There were no significant differences between the groups in terms of oxidative stress and DNA damage. Cortisol and 8-hydroxy-2-deoxyguanosine levels decreased as the time elapsed since the sexual abuse increased. Coenzyme Q level was lower in victims who sustained multiple assaults than in the victims of a single assault. Cortisol and superoxide dismutase levels were lower in the victims of familial sexual abuse. Decreases in cortisol and 8-hydroxy-2-deoxyguanosine levels as time elapsed may be an adaptation to the toxic effects of high cortisol levels over a prolonged period of time. Child sexual abuse did not result in oxidative stress and DNA damage; however, some features of sexual abuse raised the level of oxidative stress.     

Work Psychology,Women and Stress: Silence,Identity and the Boundaries of Conventional Wisdom

It is argued that there has been a close connection between work psychologists and management which has produced a discourse about stress. In this discourse workers are positioned as victims whose suffering may be overcome through behavioural technologies. Having drawn attention to the assumptions, limitations and silences of the literature, recent debates surrounding gender and the politics of identity are considered in order to outline the possibility of a complementary approach to the study of gender and work stress. Theoretical and practical issues are addressed.     

Promoting Development in Weak Institutional Environments: The Understanding and Transmission of Sustainability by NGOS in Latin America

Non-governmental organizations (NGOs) are a major institutional force in promoting sustainable development, especially in institutional environments where governments have often not been able to assume the role of development agent. Despite this importance, the approach of Latin American NGOs to sustainability has received only little attention so far and respective research is scarce. To address this research gap, we conducted an online survey of 306 Latin American NGOs, investigating their understanding of sustainability and how they seek to transmit it. Due to the lack of previous empirical studies, our study is exploratory in nature and examines eight research categories: (1) NGOs definition of sustainability; (2) the role they see for themselves in its promotion, (3) dimensions of sustainability judged as important, (4) stakeholders and (5) partners considered, (6) motives for pursuing sustainability, (7) forms of implementation, and (8) measures regarded as necessary for spreading it further. Our findings are discussed against the institutional environment of Latin America, as we assume that the understanding and transmission of sustainability is contextual in nature. Our study shows that the sustainability concept of the sample NGOs is broad and that they take a wide variety of efforts for implementing it. Exploratory and confirmatory factor analyses confirmed the reliability and validity of the eight-component-model we applied for our study. Thus, it serves as a valuable starting point for future research into the “terra incognita” of Latin American NGOs’ approach to sustainability.