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Sample records for repeatedly stressed aged

  1. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice

    Science.gov (United States)

    Buchanan, J.B.; Sparkman, N.L.; Chen, J.; Johnson, R.W.

    2008-01-01

    Summary Peripheral immune stimulation as well as certain types of psychological stress increases brain levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNFα). We have demonstrated that aged mice show greater increases in central inflammatory cytokines, as well as greater cognitive deficits, compared to adults in response to peripheral lipopolysaccharide (LPS) administration. Because aged mice are typically more sensitive to systemic stressors such as LPS, and certain psychological stressors induce physiological responses similar to those that follow LPS, we hypothesized that aged mice would be more sensitive to the physiological and cognitive effects of mild stress than adult mice. Here, adult (3–5 mo) and aged (22–23 mo) male BALB/c mice were trained in the Morris water maze for 5 days. Mice were then exposed to a mild restraint stress of 30 minutes before being tested in a working memory version of the water maze over a 3 day period. On day 4 mice were stressed and then killed for collection of blood and brain. In a separate group of animals, mice were killed immediately after one, two or three 30 min restraint sessions and blood for peripheral corticosterone and cytokine protein measurement, and brains were dissected for central cytokine mRNA measurement. Stress disrupted spatial working memory in both adult and aged mice but to a much greater extent in the aged mice. In addition, aged mice showed an increase in stress-induced expression of hippocampal IL-1β mRNA and MHC class II protein compared to non-stressed controls while expression in adult mice was unaffected by stress. These data show that aged mice are more sensitive to both the cognitive and inflammatory effects of mild stress than are adult mice and suggest a possible a role for IL-1β. PMID:18407425

  2. UV, stress and aging

    OpenAIRE

    Debacq-Chainiaux, Florence; Leduc, Cedric; Verbeke, Alix; Toussaint, Olivier

    2014-01-01

    Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic—also called "photo-aging"—resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on ...

  3. UV, stress and aging.

    Science.gov (United States)

    Debacq-Chainiaux, Florence; Leduc, Cedric; Verbeke, Alix; Toussaint, Olivier

    2012-07-01

    Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic-also called "photo-aging"-resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on the cell type (fibroblasts or keratinocytes, normal or immortalized) and the type of UV used (UVA or UVB).

  4. Oxidative stress and ageing.

    Science.gov (United States)

    Birch-Machin, M A; Bowman, A

    2016-10-01

    Oxidative stress is the resultant damage due to redox imbalances (increase in destructive free radicals [reactive oxygen species (ROS)] and reduction in antioxidant protection/pathways) and is linked to ageing in many tissues including skin. In ageing skin there are bioenergetic differences between keratinocytes and fibroblasts which provide a potential ageing biomarker. The differences in skin bioenergy are part of the mitochondrial theory of ageing which remains one of the most widely accepted ageing theories describing subsequent increasing free radical generation. Mitochondria are the major source of cellular oxidative stress and form part of the vicious cycle theory of ageing. External and internal sources of oxidative stress include UVR/IR, pollution (environment), lifestyle (exercise and diet), alcohol and smoking all of which may potentially impact on skin although many exogenous actives and endogenous antioxidant defence systems have been described to help abrogate the increased stress. This also links to differences in skin cell types in terms of the UVR action spectrum for nuclear and mitochondrial DNA damage (the latter a previously described UVR biomarker in skin). Recent work associates bioenergy production and oxidative stress with pigment production thereby providing another additional potential avenue for targeted anti-ageing intervention in skin. This new data supporting the detrimental effects of the numerous wavelengths of UVR may aid in the development of cosmetic/sunscreen design to reduce the effects of photoageing. Recently, complex II of the mitochondrial electron transport chain appears to be more important than previously thought in the generation of free radicals (suggested predominantly by non-human studies). We investigated the relationship between complex II and ageing using human skin as a model tissue. The rate of complex II activity per unit of mitochondria was determined in fibroblasts and keratinocytes cultured from skin covering

  5. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; ter Horst, J.P.; Loi, M.; den Blaauwen, J.; Bangert, E.L.; Fernández, G.; Joëls, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

  6. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Marit Arp, J; Ter Horst, Judith P; Loi, Manila; den Blaauwen, Jan; Bangert, Eline; Fernández, Guillén; Joëls, Marian; Oitzl, Melly S; Krugers, Harm

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal d

  7. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; Horst, J.P. ter; Loi, M.; Blaauwen, J. den; Bangert, E.; Fernandez, G.S.E.; Joels, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

  8. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; ter Horst, J.P.; Loi, M.; den Blaauwen, J.; Bangert, E.L.; Fernández, G.; Joëls, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal d

  9. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress

    NARCIS (Netherlands)

    Arp, J.M.; Horst, J.P. ter; Loi, M.; Blaauwen, J. den; Bangert, E.; Fernandez, G.S.E.; Joels, M.; Oitzl, M.S.; Krugers, H.J.

    2016-01-01

    Early life adversity can have long-lasting impact on learning and memory processes and increase the risk to develop stress-related psychopathologies later in life. In this study we investigated (i) how chronic early life stress (ELS) - elicited by limited nesting and bedding material from postnatal

  10. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  11. Repeatedly stressed rats have enhanced vulnerability to amygdala kindling epileptogenesis.

    Science.gov (United States)

    Jones, Nigel C; Lee, Han Ee; Yang, Meng; Rees, Sandra M; Morris, Margaret J; O'Brien, Terence J; Salzberg, Michael R

    2013-02-01

    Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n=18) or non-stressed (n=19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced ('the fully kindled state'). Stressed rats were exposed to 30min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122±17ng/ml; post-stress: 632±33ng/ml), with no habituation observed over the experiment. Stressed rats reached the 'fully kindled state' in significantly fewer stimulations than non-stressed rats (21±1 vs 33±3 stimulations; p=0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p<0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans.

  12. The stress of aging.

    Science.gov (United States)

    Cesari, Matteo; Vellas, Bruno; Gambassi, Giovanni

    2013-04-01

    Although the evolutionary theories of aging are quite well established, our knowledge about how we age is still very limited. The abundance and heterogeneity of available mechanistic theories of aging implicitly suggest that this phenomenon is overly complex and unlikely to be explained by a single pathway. Moreover, although aging remains a unique process, it is characterized by heterogeneous manifestations, not only determining inter-individual variations, but even intra-individual diversities. Such heterogeneity renders the inner nature of the aging process of difficult evaluation in older persons due to the potential biases introduced by multiple age-related social, biological, and clinical factors (and responsible for the evidence-based issue in geriatrics). Moving from the difficulties in translating anti-aging preclinical interventions into clinical trials, an alternative approach is illustrated. We encourage moving to a holistic evaluation of aging by adopting specific and consequent modifications in the design and conduction of clinical research. Such approach is today commonly applied in the clinical setting where the complexity of older patients often requires multidimensional interventions to adequately target the geriatric syndromes. Consistently, interventions targeting the aging process may result ineffective if too focused on a single underlying causal mechanism and/or failing to capture the complexity of the phenomenon. In this context, frailty (a geriatric syndrome characterized by age-related declines occurring across multiple physiologic systems) may indeed represent a clinically relevant threshold throughout the continuum of the aging process and a promising benchmark to test multidomain interventions against age-related conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    Science.gov (United States)

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits.

  14. Heat stress impairs repeated jump ability after competitive elite soccer games

    DEFF Research Database (Denmark)

    Mohr, Magni; Krustrup, Peter

    2013-01-01

    ABSTRACT:: The present study examined the effect of environmental heat stress on repeated jump performance after elite competitive soccer games. Male elite soccer players (n=19) from two Scandinavian teams participated (age; 26.7±1.0 yrs, height; 181.7±1.1 cm, body mass; 75.8±1.0 kg). The players...

  15. Age, CAG repeat length, and clinical progression in Huntington's disease.

    Science.gov (United States)

    Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa; Welsh, Claire S; Margolis, Russell L; Ross, Christopher A

    2012-02-01

    The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.

  16. Skin aging and oxidative stress

    OpenAIRE

    Sayeeda Ahsanuddin; Minh Lam; Baron, Elma D.

    2016-01-01

    Skin aging occurs through two main pathways, intrinsic and extrinsic. These pathways have significant interaction in contributing to the aging phenotype, which includes skin laxity, wrinkling, pigmentation irregularities, and the appearance of neoplastic skin lesions. Here, we review the critical role that oxidative stress plays in skin aging, including its effects on signaling pathways involved in skin matrix formation and degradation, proteasome activity, as well as DNA structure. Furthermo...

  17. Distinct effects of repeated restraint stress on basolateral amygdala neuronal membrane properties in resilient adolescent and adult rats.

    Science.gov (United States)

    Hetzel, Andrea; Rosenkranz, J Amiel

    2014-08-01

    Severe and repeated stress has damaging effects on health, including initiation of depression and anxiety. Stress that occurs during development has long-lasting and particularly damaging effects on emotion. The basolateral amygdala (BLA) plays a key role in many affective behaviors, and repeated stress causes different forms of BLA hyperactivity in adolescent and adult rats. However, the mechanism is not known. Furthermore, not every individual is susceptible to the negative consequences of stress. Differences in the effects of stress on the BLA might contribute to determine whether an individual will be vulnerable or resilient to the effects of stress on emotion. The purpose of this study is to test the cellular underpinnings for age dependency of BLA hyperactivity after stress, and whether protective changes occur in resilient individuals. To test this, the effects of repeated stress on membrane excitability and other membrane properties of BLA principal neurons were compared between adult and adolescent rats, and between vulnerable and resilient rats, using in vitro whole-cell recordings. Vulnerability was defined by adrenal gland weight, and verified by body weight gain after repeated restraint stress, and fecal pellet production during repeated restraint sessions. We found that repeated stress increased the excitability of BLA neurons, but in a manner that depended on age and BLA subnucleus. Furthermore, stress resilience was associated with an opposite pattern of change, with increased slow afterhyperpolarization (AHP) potential, whereas vulnerability was associated with decreased medium AHP. The opposite outcomes in these two populations were further distinguished by differences of anxiety-like behavior in the elevated plus maze that were correlated with BLA neuronal excitability and AHP. These results demonstrate a substrate for BLA hyperactivity after repeated stress, with distinct membrane properties to target, as well as age-dependent factors that

  18. Repeatability of OCT lens thickness measures with age and accommodation.

    Science.gov (United States)

    Doyle, Lesley; Little, Julie-Anne; Saunders, Kathryn J

    2013-12-01

    To investigate crystalline lens thickness (LT) across a range of ages and accommodative demands and to evaluate the repeatability of LT measurements using the Visante Anterior Segment Optical Coherence Tomographer (AS-OCT) (Zeiss Meditec, Germany) under non-cycloplegic conditions. Participants were 98 visually normal adults aged 18-75 years, stratified into age groups of 18-29, 30-39, 40-49, 50-59, and 60-75 years of age. Images of the crystalline lens were taken using the Visante AS-OCT during stimulation of accommodation at demands of 0, 1, 2, 3, 4, 5, and 8 D with accommodative response measured in a subgroup of participants. Images were analyzed and LT measured assuming a refractive index of 1.42. Repeat measures were taken from 86 participants for each accommodative demand at a second visit. The mean unaccommodated LT for all participants was 4.07 ± 0.40 mm. An average increase in LT of 20 μm per year was calculated (linear regression, R² = 0.61, F(1,89) = 143.92, p report the repeatability of LT measures using the Visante AS-OCT in the non-cyclopleged eye. It has also demonstrated the ability of the Visante AS-OCT to detect small changes in lens thickness with accommodation.

  19. Post-stress rumination predicts HPA axis responses to repeated acute stress.

    Science.gov (United States)

    Gianferante, Danielle; Thoma, Myriam V; Hanlin, Luke; Chen, Xuejie; Breines, Juliana G; Zoccola, Peggy M; Rohleder, Nicolas

    2014-11-01

    Failure of the hypothalamus-pituitary-adrenal (HPA) axis to habituate to repeated stress exposure is related with adverse health outcomes, but our knowledge of predictors of non-habituation is limited. Rumination, defined as repetitive and unwanted past-centered negative thinking, is related with exaggerated HPA axis stress responses and poor health outcomes. The aim of this study was to test whether post-stress rumination was related with non-habituation of cortisol to repeated stress exposure. Twenty-seven participants (n=13 females) were exposed to the Trier Social Stress Test (TSST) twice on consecutive afternoons. Post-stress rumination was measured after the first TSST, and HPA axis responses were assessed by measuring salivary cortisol 1 min before, and 1, 10, 20, 60, and 120 min after both TSSTs. Stress exposure induced HPA axis activation on both days, and this activation showed habituation indicated by lower responses to the second TSST (F=3.7, p=0.015). Post-stress rumination after the first TSST was associated with greater cortisol reactivity after the initial stress test (r=0.45, pHPA axis responses. This finding implicates rumination as one possible mechanism mediating maladaptive stress response patterns, and it might also offer a pathway through which rumination might lead to negative health outcomes.

  20. Influence of repeated daily diving on decompression stress.

    Science.gov (United States)

    Zanchi, J; Ljubkovic, M; Denoble, P J; Dujic, Z; Ranapurwala, S; Pollock, N W

    2014-06-01

    Acclimatization (an adaptive change in response to repeated environmental exposure) to diving could reduce decompression stress. A decrease in post-dive circulating venous gas emboli (VGE or bubbles) would represent positive acclimatization. The purpose of this study was to determine whether four days of daily diving alter post-dive bubble grades. 16 male divers performed identical no-decompression air dives on 4 consecutive days to 18 meters of sea water for 47 min bottom times. VGE monitoring was performed with transthoracic echocardiography every 20 min for 120 min post-dive. Completion of identical daily dives resulted in progressively decreasing odds (or logit risk) of having relatively higher grade bubbles on consecutive days. The odds on Day 4 were half that of Day 1 (OR 0.50, 95% CI: 0.34, 0.73). The odds ratio for a >III bubble grade on Day 4 was 0.37 (95% CI: 0.20, 0.70) when compared to Day 1. The current study indicates that repetitive daily diving may reduce bubble formation, representing a positive (protective) acclimatization to diving. Further work is required to evaluate the impact of additional days of diving and multiple dive days and to determine if the effect is sufficient to alter the absolute risk of decompression sickness.

  1. Protein stress and stress proteins: implications in aging and disease

    Indian Academy of Sciences (India)

    C Sőti; Péter Csermely

    2007-04-01

    Environmantal stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so called stress or heat shock proteins. The stress response as well as stress proteins are ubiquitous, highly conserved mechanism, and genes, respectively, already present in prokaryotes. Chaperones protect the proteome against conformational damage, promoting the function of protein networks. Protein damage takes place during aging and in several degenerative diseases, and presents a threat to overload the cellular defense mechanisms. The preservation of a robust stress response and protein disposal is indispensable for health and longevity. This review summarizes the present knowledge of protein damage, turnover, and the stress response in aging and degenerative diseases.

  2. Social support, stress and the aging brain.

    Science.gov (United States)

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress.

  3. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition.

    Science.gov (United States)

    Wei, J; Yuen, E Y; Liu, W; Li, X; Zhong, P; Karatsoreos, I N; McEwen, B S; Yan, Z

    2014-05-01

    Converging evidence suggests that females and males show different responses to stress; however, little is known about the mechanism underlying the sexually dimorphic effects of stress. In this study, we found that young female rats exposed to 1 week of repeated restraint stress show no negative effects on temporal order recognition memory (TORM), a cognitive process controlled by the prefrontal cortex (PFC), which was contrary to the impairment in TORM observed in stressed males. Concomitantly, normal glutamatergic transmission and glutamate receptor surface expression in PFC pyramidal neurons were found in repeatedly stressed females, in contrast to the significant reduction seen in stressed males. The detrimental effects of repeated stress on TORM and glutamate receptors were unmasked in stressed females when estrogen receptors were inhibited or knocked down in PFC, and were prevented in stressed males with the administration of estradiol. Blocking aromatase, the enzyme for the biosynthesis of estrogen, revealed the stress-induced glutamatergic deficits and memory impairment in females, and the level of aromatase was significantly higher in the PFC of females than in males. These results suggest that estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and PFC-dependent cognition, which may underlie the stress resilience of females.

  4. Aging is not a barrier to muscle and redox adaptations: applying the repeated eccentric exercise model.

    Science.gov (United States)

    Nikolaidis, Michalis G; Kyparos, Antonios; Spanou, Chrysa; Paschalis, Vassilis; Theodorou, Anastasios A; Panayiotou, George; Grivas, Gerasimos V; Zafeiridis, Andreas; Dipla, Konstantina; Vrabas, Ioannis S

    2013-08-01

    Despite the progress of analytic techniques and the refinement of study designs, striking disagreement exists among studies regarding the influence of exercise on muscle function and redox homeostasis in the elderly. The repeated eccentric exercise model was applied to produce long-lasting and extensive changes in redox biomarkers and to reveal more effectively the potential effects of aging on redox homeostasis. Ten young (20.6±0.5 years) and ten elderly men (64.6±1.1 years) underwent an isokinetic eccentric exercise session, which was repeated after three weeks. Muscle function/damage indices (torque, range of movement, muscle soreness and creatine kinase) and redox biomarkers (F2-isoprostanes, protein carbonyls, glutathione, catalase, superoxide dismutase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, uric acid, bilirubin and albumin) were assessed in plasma, erythrocytes or urine pre-exercise, immediately post-exercise and at 2 and 4 days post-exercise. As expected, the elderly group exhibited oxidative stress in baseline compared to the young group. Extensive muscle damage and extensive alterations in redox homeostasis appeared after the first bout of eccentric exercise. Noteworthy, the redox responses were similar between the age groups despite their differences in baseline values. Likewise, both age groups demonstrated blunted alterations in muscle damage and redox homeostasis after the second bout of eccentric exercise indicating adaptations from the first bout of exercise. Elderly individuals seem to be well fitted to participate in demanding physical activities without suffering detrimental effects on skeletal muscle and/or disturbances on redox homeostasis. The repeated eccentric exercise model may be a useful and practical physiological tool to study redox biology in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  6. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  7. Habituation to repeated stress: get used to it.

    OpenAIRE

    Grissom, Nicola; Bhatnagar, Seema

    2008-01-01

    Habituation, as described in the landmark paper by Thompson and Spencer (1966), is a form of simple, nonassociative learning in which the magnitude of the response to a specific stimulus decreases with repeated exposure to that stimulus. A variety of neuronal and behavioral responses have been shown to be subject to habituation based on the criteria presented in that paper. It has been known for several decades that the magnitude of hypothalamic-pituitary-adrenal (HPA) activation occurring in...

  8. Mechanical Alterations Associated with Repeated Treadmill Sprinting under Heat Stress

    Science.gov (United States)

    Brocherie, Franck; Morin, Jean-Benoit; Racinais, Sébastien; Millet, Grégoire P.; Périard, Julien D.

    2017-01-01

    Purpose Examine the mechanical alterations associated with repeated treadmill sprinting performed in HOT (38°C) and CON (25°C) conditions. Methods Eleven recreationally active males performed a 30-min warm-up followed by three sets of five 5-s sprints with 25-s recovery and 3-min between sets in each environment. Constant-velocity running for 1-min at 10 and 20 km.h-1 was also performed prior to and following sprinting. Results Mean skin (37.2±0.7 vs. 32.7±0.8°C; P<0.001) and core (38.9±0.2 vs. 38.8±0.3°C; P<0.05) temperatures, together with thermal comfort (P<0.001) were higher following repeated sprinting in HOT vs. CON. Step frequency and vertical stiffness were lower (-2.6±1.6% and -5.5±5.5%; both P<0.001) and contact time (+3.2±2.4%; P<0.01) higher in HOT for the mean of sets 1–3 compared to CON. Running distance per sprint decreased from set 1 to 3 (-7.0±6.4%; P<0.001), with a tendency for shorter distance covered in HOT vs. CON (-2.7±3.4%; P = 0.06). Mean vertical (-2.6±5.5%; P<0.01), horizontal (-9.1±4.4%; P<0.001) and resultant ground reaction forces (-3.0±2.8%; P<0.01) along with vertical stiffness (-12.9±2.3%; P<0.001) and leg stiffness (-8.4±2.7%; P<0.01) decreased from set 1 to 3, independently of conditions. Propulsive power decreased from set 1 to 3 (-16.9±2.4%; P<0.001), with lower propulsive power values in set 2 (-6.6%; P<0.05) in HOT vs. CON. No changes in constant-velocity running patterns occurred between conditions, or from pre-to-post repeated-sprint exercise. Conclusions Thermal strain alters step frequency and vertical stiffness during repeated sprinting; however without exacerbating mechanical alterations. The absence of changes in constant-velocity running patterns suggests a strong link between fatigue-induced velocity decrements during sprinting and mechanical alterations. PMID:28146582

  9. Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging?

    Science.gov (United States)

    Salmon, Adam B; Richardson, Arlan; Pérez, Viviana I

    2010-03-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is life span, i.e., does altering oxidative stress/damage change life span? Mice with genetic manipulations in their antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in life span. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory: increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean that (a) oxidative stress plays a very limited, if any, role in aging but a major role in health span and/or (b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an "antiaging" action, leading to changes in life span, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging.

  10. Work stress in aging police officers.

    Science.gov (United States)

    Gershon, Robyn R M; Lin, Susan; Li, Xianbin

    2002-02-01

    Data are sparse regarding the impact of psychosocial work stress on the health and well-being of aging workers, even for employees working in high-stress occupations, such as law enforcement. To improve our understanding of this issue in older workers, we assessed and characterized work stress, coping strategies, and stress-related health outcomes in a sample of police officers aged 50 years and older (n = 105). The most important risk factors associated with officers' perceived work stress were maladaptive coping behaviors (e.g., excessive drinking or problem gambling) (odds ratio [OR], 4.95; 95% confidence interval [CI], 2.11 to 11.6) and exposure to critical incidents (e.g., shootings) (OR, 3.84; 95% CI, 1.71 to 8.65). In turn, perceived work stress was significantly associated with anxiety (OR, 6.84; 95% CI, 2.81 to 16.65), depression (OR, 9.27; 95% CI, 3.81 to 22.54), somatization (OR, 5.74; 95% CI, 2.47 to 13.33), posttraumatic stress symptoms (OR, 2.89; 95% CI, 1.29 to 6.47), symptoms of "burnout" (OR, 5.93; 95% CI, 2.54 to 13.86), chronic back pain (OR, = 3.55; 95% CI, 1.57 to 8.06), alcohol abuse (OR, 3.24; 95% CI, 1.45 to 7.22), and inappropriately aggressive behavior (OR, 4.00; 95% CI, 1.34 to 11.88). These data suggest that older workers in high-stress jobs may be at increased risk for work stress-related health problems, especially if they rely on risky health behaviors to cope with stress. Given the size of the rapidly aging US workforce and the likelihood that many are employed in high-stress jobs, interventions are urgently needed to address this emerging public health issue.

  11. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H;

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...... implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs....

  12. Repeated stressful experiences differently affect brain dopamine receptor subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Puglisi-Allegra, S.; Cabib, S. (Istituto di Psicobiologia e Psicofarmacologia (CNR), Roma (Italy)); Kempf, E.; Schleef, C. (Centre de Neurochimi, Strasbourg (Italy))

    1991-01-01

    The binding of tritiated spiperone (D2 antagonist) and tritiated SCH 23390 (D1 antagonist), in vivo, was investigated in the caudatus putamen (CP) and nucleus accumbens septi (NAS) of mice submitted to ten daily restraint stress sessions. Mice sacrificed 24 hr after the last stressful experience presented a 64% decrease of D2 receptor density (Bmax) but no changes in D1 receptor density in the NAS. In the CP a much smaller (11%) reduction of D2 receptor density was accompanied by a 10% increase of D1 receptors. These results show that the two types of dopamine (DA) receptors adapt in different or even opposite ways to environmental pressure, leading to imbalance between them.

  13. [Telomere length, telomerase activity, stress and aging].

    Science.gov (United States)

    Spivak, I M; Mikhelson, V M; Spivak, D L

    2015-01-01

    The review is dedicated to analysis of data available at present time concerning possible influence of stress upon telomere lengths and telomerase activity, as well as various ways of counteracting it. Present-day telomerase theory of aging gains a new impetus, shedding light upon the influence of psychological state of humans and their ability to counteract stress, upon the process of aging. It also tends to regard telomere shortening and the decrease in the activity of telomerase as a marker of level of the ability to adapt to both inner and outer influences. Both aging and age-dependent diseases are proved to be substantially retarded not only by the administration of drugs, but also by psychological means, which forms a good way towards healthy longevity. With complete understanding of the impossibility to prevent or even to slow down natural senescence itself, these methods allow to remove causes, which accelerate senescence, and to increase the average human longevity.

  14. Over-representation of repeats in stress response genes: a strategy to increase versatility under stressful conditions?

    Science.gov (United States)

    Rocha, Eduardo P C; Matic, Ivan; Taddei, François

    2002-05-01

    The survival of individual organisms facing stress is enhanced by the induction of a set of changes. As the intensity, duration and nature of stress is highly variable, the optimal response to stress may be unpredictable. To face such an uncertain future, it may be advantageous for a clonal population to increase its phenotypic heterogeneity (bet-hedging), ensuring that at least a subset of cells would survive the current stress. With current techniques, assessing the extent of this variability experimentally remains a challenge. Here, we use a bioinformatic approach to compare stress response genes with the rest of the genome for the presence of various kinds of repeated sequences, elements known to increase variability during the transfer of genetic information (i.e. during replication, but also during gene expression). We investigated the potential for illegitimate and homologous recombination of 296 Escherichia coli genes related to repair, recombination and physiological adaptations to different stresses. Although long repeats capable of engaging in homologous recombination are almost absent in stress response genes, we observed a significant high number of short close repeats capable of inducing phenotypic variability by slipped-mispair during DNA, RNA or protein synthesis.

  15. Exaggerated phosphorylation of brain tau protein in CRH KO mice exposed to repeated immobilization stress.

    Science.gov (United States)

    Kvetnansky, Richard; Novak, Petr; Vargovic, Peter; Lejavova, Katarina; Horvathova, Lubica; Ondicova, Katarina; Manz, George; Filipcik, Peter; Novak, Michal; Mravec, Boris

    2016-07-01

    Neuroendocrine and behavioral stress responses are orchestrated by corticotropin-releasing hormone (CRH) and norepinephrine (NE) synthesizing neurons. Recent findings indicate that stress may promote development of neurofibrillary pathology in Alzheimer's disease. Therefore, we investigated relationships among stress, tau protein phosphorylation, and brain NE using wild-type (WT) and CRH-knockout (CRH KO) mice. We assessed expression of phosphorylated tau (p-tau) at the PHF-1 epitope and NE concentrations in the locus coeruleus (LC), A1/C1 and A2/C2 catecholaminergic cell groups, hippocampus, amygdala, nucleus basalis magnocellularis, and frontal cortex of unstressed, singly stressed or repeatedly stressed mice. Moreover, gene expression and protein levels of tyrosine hydroxylase (TH) and CRH receptor mRNA were determined in the LC. Plasma corticosterone levels were also measured. Exposure to a single stress increases tau phosphorylation throughout the brain in WT mice when compared to singly stressed CRH KO animals. In contrast, repeatedly stressed CRH KO mice showed exaggerated tau phosphorylation relative to WT controls. We also observed differences in extent of tau phosphorylation between investigated structures, e.g. the LC and hippocampus. Moreover, CRH deficiency leads to different responses to stress in gene expression of TH, NE concentrations, CRH receptor mRNA, and plasma corticosterone levels. Our data indicate that CRH effects on tau phosphorylation are dependent on whether stress is single or repeated, and differs between brain regions. Our findings indicate that CRH attenuates mechanisms responsible for development of stress-induced tau neuropathology, particularly in conditions of chronic stress. However, the involvement of central catecholaminergic neurons in these mechanisms remains unclear and is in need of further investigation.

  16. Myricetin Attenuates Depressant-Like Behavior in Mice Subjected to Repeated Restraint Stress

    Directory of Open Access Journals (Sweden)

    Zegang Ma

    2015-11-01

    Full Text Available Increasing evidence has shown that oxidative stress may be implicated in chronic stress-induced depression. Several flavonoids with anti-oxidative effects have been proved to be anti-depressive. Myricetin is a well-defined flavonoid with the anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective properties. The aim of the present study is to investigate the possible effects of chronic administration of myricetin on depressant-like behaviors in mice subjected to repeated restraint (4 h/day for 21 days. Our results showed that myricetin administration specifically reduced the immobility time in mice exposed to chronic stress, as tested in both forced swimming test and tail suspension test. Myricetin treatment improved activities of glutathione peroxidase (GSH-PX in the hippocampus of stressed mice. In addition, myricetin treatment decreased plasma corticosterone levels of those mice subjected to repeated restraint stress. The effects of myricetin on the brain-derived neurotrophic factor (BDNF levels in hippocampus were also investigated. The results revealed that myricetin normalized the decreased BDNF levels in mice subjected to repeated restraint stress. These findings provided more evidence that chronic administration of myricetin improves helpless behaviors. The protective effects of myricetin might be partially mediated by an influence on BDNF levels and might be attributed to myricetin-mediated anti-oxidative stress in the hippocampus.

  17. Age differences in stress and coping processes.

    Science.gov (United States)

    Folkman, S; Lazarus, R S; Pimley, S; Novacek, J

    1987-06-01

    The dramatic increase in the numbers of people who are living into old age has been accompanied by a growing interest among psychologists and health care professionals in their sources of stress and how they cope with them. Despite this interest, little is known about normative stress and coping patterns and the ways in which these patterns differ in older and younger people. This study, which draws on stress and coping theory, compares younger and older community-dwelling adults in daily hassles and eight kinds of coping. Two interpretations of age differences are evaluated: a developmental interpretation, which says that there are inherent, stage-related changes in the ways people cope as they age, and a contextual interpretation, which says that age differences in coping result from changes in what people must cope with. The findings indicate that there are clear age differences in hassles and coping. Overall, the findings tend to support the developmental interpretation, although the contextual interpretation also applies.

  18. Social context, stress, and plasticity of aging.

    Science.gov (United States)

    Amdam, Gro V

    2011-02-01

    Positive social contact is an important factor in healthy aging, but our understanding of how social interactions influence senescence is incomplete. As life expectancy continues to increase because of reduced death rates among elderly, the beneficial role of social relationships is emerging as a cross-cutting theme in research on aging and healthspan. There is a need to improve knowledge on how behavior shapes, and is shaped by, the social environment, as well as needs to identify and study biological mechanisms that can translate differences in the social aspects of behavioral efforts, relationships, and stress reactivity (the general physiological and behavioral response-pattern to harmful, dangerous or unpleasant situations) into variation in aging. Honey bees (Apis mellifera) provide a genetic model in sociobiology, behavioral neuroscience, and gerontology that is uniquely sensitive to social exchange. Different behavioral contact between these social insects can shorten or extend lifespan more than 10-fold, and some aspects of their senescence are reversed by social cues that trigger aged individuals to express youthful repertoires of behavior. Here, I summarize how variation in social interactions contributes to this plasticity of aging and explain how beneficial and detrimental roles of social relationships can be traced from environmental and biological effects on honey bee physiology and behavior, to the expression of recovery-related plasticity, stress reactivity, and survival during old age. This system provides intriguing opportunities for research on aging.

  19. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice

    Science.gov (United States)

    Hassan, Ahmed M.; Jain, Piyush; Reichmann, Florian; Mayerhofer, Raphaela; Farzi, Aitak; Schuligoi, Rufina; Holzer, Peter

    2014-01-01

    Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis. PMID:25414650

  20. Repeated Predictable Stress Causes Resilience against Colitis-Induced Behavioral Changes in Mice

    Directory of Open Access Journals (Sweden)

    Ahmed M Hassan

    2014-11-01

    Full Text Available Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2 % in drinking water decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and social interaction tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY, a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.

  1. [Ageing free radicals and cellular stress].

    Science.gov (United States)

    Barouki, Robert

    2006-03-01

    A number of theories have attempted to account for ageing processes in various species. Following the theory of Pearl, Harman suggested fifty years ago that the accumulation of oxidants could explain the alteration of physical and cognitive functions with ageing. Oxygen metabolism leads to reactive species, including free radicals, which tend to oxidize surrounding molecules such as DNA, proteins and lipids. As a consequence various functions of cells and tissues can be altered, leading to DNA instability, protein denaturation and accumulation of lipid byproducts. Oxidative stress is an adaptive process which is triggered upon oxidant accumulation and which comprises the induction of protective and survival functions. Experimental evidence suggests that the ageing organism is in a state of oxidative stress, which supports the free radical theory. A number of other theories have been proposed ; some of these are actually compatible with the free radical theory. Caloric restriction is among the best models to increase life span in many species. While the relationship between caloric restriction and corrected metabolic rate is controversial, the decrease in ROS production by mitochondria appears to be experimentally supported. The ROS and mitochondrial theories of ageing appear to be compatible. Genetic models of increased life span, particularly those affecting the Foxo pathway, are usually accompanied by an increased resistance to oxidative insult. The free radical theory is not consistent with programmed senescence theories involving the cell division dependent decrease in telomere length ; however, oxidants are known to alter telomere structure. An appealing view of the role of oxidative stress in ageing is the trade-off principle which states that a phenotypic trait can be evolutionarily conserved because of its positive effects on development, growth or fertility, and despite its negative effect on somatic functions and ageing. It is likely that most cellular

  2. Repeated stress increases catalytic TrkB mRNA in rat hippocampus.

    Science.gov (United States)

    Nibuya, M; Takahashi, M; Russell, D S; Duman, R S

    1999-05-28

    Northern blot analysis was utilized to distinguish between catalytic and truncated TrkB mRNA on the basis of transcript size. Repeated (10 days), but not acute, immobilization stress significantly increased levels of catalytic TrkB mRNA, but did not influence expression of truncated TrkB transcripts in rat hippocampus. Exposure to another paradigm, a combination of different, unpredictable stressors, also increased levels of catalytic, but not truncated, TrkB mRNA. In situ hybridization analysis demonstrated that chronic stress up-regulated TrkB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus. As previously reported, both acute and chronic immobilization stress decreased expression of BDNF mRNA, suggesting that up-regulation of catalytic TrkB mRNA may be a compensatory adaptation to repeated stress.

  3. Changes in Liver Proteome Expression of Senegalese Sole (Solea senegalensis) in Response to Repeated Handling Stress

    DEFF Research Database (Denmark)

    Cordeiro, O. D.; Silva, Tomé Santos; Alves, R. N.

    2012-01-01

    the detection of 287 spots significantly affected by repeated handling stress (Wilcoxon–Mann–Whitney U test, p stress seems to have affected protein synthesis, folding and turnover (40S ribosomal protein S12...... hormone metabolism (3-oxo-5-β-steroid 4-dehydrogenase), and purine salvage (hypoxanthine phosphoribosyltransferase). Further characterization is required to fully assess the potential of these markers for the monitoring of fish stress response to chronic stressors of aquaculture environment.......The Senegalese sole, a high-value flatfish, is a good candidate for aquaculture production. Nevertheless, there are still issues regarding this species’ sensitivity to stress in captivity. We aimed to characterize the hepatic proteome expression for this species in response to repeated handling...

  4. Epigenetics and Oxidative Stress in Aging

    Directory of Open Access Journals (Sweden)

    Amy Guillaumet-Adkins

    2017-01-01

    Full Text Available Aging is a multifactorial process characterized by the progressive loss of physiological functions, leading to an increased vulnerability to age-associated diseases and finally to death. Several theories have been proposed to explain the nature of aging. One of the most known identifies the free radicals produced by the mitochondrial metabolism as the cause of cellular and DNA damage. However, there are also several evidences supporting that epigenetic modifications, such as DNA methylation, noncoding RNAs, and histone modifications, play a critical role in the molecular mechanism of aging. In this review, we explore the significance of these findings and argue how the interlinked effects of oxidative stress and epigenetics can explain the cause of age-related declines.

  5. Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

    Science.gov (United States)

    Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

    2017-02-01

    The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

  6. Physiological responses to repeated stress in individuals with high and low trait resilience.

    Science.gov (United States)

    Lü, Wei; Wang, Zhenhong; You, Xuqun

    2016-10-01

    This study examined individual differences in trait resilience in physiological recovery from, and physiological habituation to, repeated stress (i.e. public speaking). Eighty-two college students were categorized as either high (n=40) or low (n=42) on trait resilience, based on the scores of the Connor-Davidson Resilience Scale (CD-RISC). Subjective and physiological data were collected from participants across seven laboratory stages: baseline, stress anticipation 1, stress 1, post-stress 1, stress anticipation 2, stress 2, and post-stress 2. Results indicated that high-trait-resilient participants exhibited more complete heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) recovery from the first and second stress anticipation exposures as compared to low-trait-resilient participants. High-trait-resilient participants demonstrated higher resting respiratory sinus arrhythmia (RSA) coupled with more complete RSA recovery from the first and second stress anticipation exposures as compared to their low-trait-resilient counterparts. Moreover, high-trait-resilient participants exhibited pronounced SBP and DBP habituation across two successive stress anticipation exposures, with greater decreases in SBP and DBP reactivity to recurrent stress anticipation as compared to the low-trait-resilient participants. These findings suggest an adaptive physiological response pattern to recurrent stress in high-trait-resilient individuals. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. The estrous cycle of the ewe is resistant to disruption by repeated, acute psychosocial stress.

    Science.gov (United States)

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Tilbrook, Alan J; Karsch, Fred J

    2010-06-01

    Five experiments were conducted to test the hypothesis that psychosocial stress interferes with the estrous cycle of sheep. In experiment 1, ewes were repeatedly isolated during the follicular phase. Timing, amplitude, and duration of the preovulatory luteinizing hormone (LH) surge were not affected. In experiment 2, follicular-phase ewes were subjected twice to a "layered stress" paradigm consisting of sequential, hourly application of isolation, restraint, blindfold, and predator cues. This reduced the LH pulse amplitude but did not affect the LH surge. In experiment 3, different acute stressors were given sequentially within the follicular phase: food denial plus unfamiliar noises and forced exercise, layered stress, exercise around midnight, and transportation. This, too, did not affect the LH surge. In experiment 4, variable acute psychosocial stress was given every 1-2 days for two entire estrous cycles; this did not disrupt any parameter of the cycle monitored. Lastly, experiment 5 examined whether the psychosocial stress paradigms of experiment 4 would disrupt the cycle and estrous behavior if sheep were metabolically stressed by chronic food restriction. Thirty percent of the food-restricted ewes exhibited deterioration of estrous cycle parameters followed by cessation of cycles and failure to express estrous behavior. However, disruption was not more evident in ewes that also encountered psychosocial stress. Collectively, these findings indicate the estrous cycle of sheep is remarkably resistant to disruption by acute bouts of psychosocial stress applied intermittently during either a single follicular phase or repeatedly over two estrous cycles.

  8. Repeating seismicity in the shallow crust modulated by transient stress perturbations

    Science.gov (United States)

    Frank, William B.; Shapiro, Nikolaï M.; Husker, Allen L.; Kostoglodov, Vladimir; Campillo, Michel

    2016-09-01

    Recent studies have reported seismic phenomena that are modulated by small stress perturbations (∼10 kPa), revealing their critically stressed nature. Such observations have been principally limited to plate interfaces with their occurrence linked to high fluid pore-pressure. In this study, we report observations of nine repeating seismic sources in the shallow crust in Guerrero, Mexico that emit events at rates comparable to other seismic phenomena in low stress environments. Testing their susceptibility to small stress perturbations, we find that all nine sources appear to be modulated by mining activity, tides, and a large slow slip event (Mw 7.5). Our results suggest that the fault conditions necessary for low effective stress seismicity can occur away from plate interfaces.

  9. Facilitation of hypothalamic-pituitary-adrenal responses to novel stress following repeated social stress using the resident/intruder paradigm.

    Science.gov (United States)

    Bhatnagar, Seema; Vining, Courtenay

    2003-01-01

    Our goal in these studies was to characterize some specific aspects of hypothalamic-pituitary-adrenal (HPA) activity in rats exposed to repeated social stress. We used a modification of the resident/intruder paradigm in which male intruder rats were subjected to defeat and then separated from the resident by an enclosure for a total of 30 min on Day 1. On Days 2-7, intruder rats were exposed to different resident rats every day through a wire mesh enclosure for 30 min in order to minimize injurious physical contact between the two rats. The intruder rats gained significantly less weight than controls over the 7-day period of stress though basal corticosterone levels and adrenal and thymus weights were not significantly different between the two groups. On Day 8, repeatedly stressed rats exhibited facilitation of HPA responses to novel restraint compared to controls but no differences in negative feedback sensitivity to dexamethasone (0.05 or 0.2 mg/kg) were observed. Thus, the HPA axis of socially stressed rats remains responsive to a stimulus that has never been encountered. Using this type of repeated presentation to an aggressive resident allows us to examine the neuroendocrine and behavioral consequences, and their underlying neural mechanisms, of exposure to a stressor that is social in nature and naturalistic for rodents.

  10. Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder.

    Science.gov (United States)

    Åhs, Fredrik; Gingnell, Malin; Furmark, Tomas; Fredrikson, Mats

    2017-03-30

    Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy.

  11. Behavioural, endocrine and immune responses to repeated social stress in pregnant gilts.

    Science.gov (United States)

    Couret, D; Otten, W; Puppe, B; Prunier, A; Merlot, E

    2009-01-01

    Pregnant sows are exposed to various stressors in intensive pig husbandry that may have negative consequences on their health, reproductive performances and welfare. Social stress is one of these challenges, because gestating sows have to be housed in groups according to EU guidelines (2001/88/CE). The purpose of this study was to determine the consequences of repeated social stress in pregnant female pigs on their behavioural, endocrine and immunological responses and on pregnancy outcome. Pregnant gilts were submitted to a repeated social stress procedure induced by housing unfamiliar gilts in pairs changed twice a week between days 77 and 105 of gestation (S group, n = 18). Control gilts were housed in stable pairs during the same period (C group, n = 18). Agonistic behaviour was observed during the first 3 h after each grouping. Skin lesions were numbered 2 h after each grouping. Salivary cortisol was measured before and repeatedly during the 4 weeks of grouping. Gilts were immunized against keyhole limpet haemocyanin (KLH) on days 81 and 95 of gestation. Immunoglobulins G against KLH, proliferative responses to concanavalin A, lipopolysaccharide, pokeweed mitogen and KLH and peripheral blood leukocyte numbers were evaluated 1 week before the first grouping and 3 days after the last one. Agonistic interactions and skin lesions were observed in S gilts at each grouping, although there was a decline between the first and the last grouping (P Gestation length tended to be shorter in S gilts (P = 0.09), but litter size, piglet weight or mortality at birth were not affected. Variability of the response of S gilts to groupings was partly explained by their average success value determined according to the outcome (defeat or win) of all the groupings. In conclusion, our study demonstrates that the application of repeated social stress to pregnant gilts during the last third of their gestation repeatedly activates their hypothalamo-pituitary-adrenal axis but does not

  12. Multifactor stress aging of electrical insulation

    Science.gov (United States)

    Laghari, Javaid R.

    1990-11-01

    Capacitor-grade polypropylene films were aged under multiple stresses (electrical, thermal, radiation) using a 2MW thermal nuclear reactor. Thermal and electrical stresses were found to slightly decrease both the AC and DC breakdown voltages. Radiation stresses were found to increase the breakdown voltages. The same trends were seen in volume resistivity. The radiation effects dominate both the thermal and electrical effects and are attributed to increased crystallinity of the polypropylene. However, mechanical properties are significantly degraded by radiation damage, and degree of breakdown enhancements are seen for combined stresses. Computer simulation has been performed showing the magnitude of the neutrine signal from a 100 kilocurie tritium source, under the geometrical conditions of the experiments at Los Angeles National Laboratory, TA-33, is about an order of magnitude smaller than the gravity signal from a 2600 gr mass (the assumed value for the mass of the source). The observations were performed by using Professor Joe Weber's torsion balance, a room-temperature instrument.

  13. Contrasting effects of diazepam and repeated restraint stress on latent inhibition in mice.

    Science.gov (United States)

    Mongeau, Raymond; Marcello, Stefania; Andersen, Jacob Sparre; Pani, Luca

    2007-11-02

    The effects on latent inhibition (LI; a delay in conditioning when a CS has been pre-exposed without consequences) of repeated restraint stress and the anxiolytic drug diazepam were examined in C57BL/6 mice to know whether previous aversive events or anxiolysis are factors determining the expression of LI. The LI model was optimized for this strain particularly sensitive to stress (using both the CER and the conditioned freezing procedures) and characterized with typical (haloperidol) and atypical (clozapine and olanzapine) antipsychotic drugs administered either during the conditioning or the pre-exposure phases. An acute challenge with amphetamine, a dopamine releaser, was done to verify the enhancement of hyperactivity in C57BL/6 mice after the restraint stress sensitization. At all doses tested, diazepam decreased latent inhibition when administered during the pre-exposure phase (similarly to atypical antipsychotic drugs). Repeated restraint stress enhanced LI by blocking the CS-induced freezing in pre-exposed mice. In contrast, pre-treatment with diazepam before pre-exposure allowed the expression of CS-induced freezing in stressed mice pre-exposed to the tone. It is suggested that stress and anxiolytic drugs can have opposite effects on attention or perseveration processes during learning of conflicting contingency responses.

  14. Repeated forced swim stress differentially affects formalin-evoked nociceptive behaviour and the endocannabinoid system in stress normo-responsive and stress hyper-responsive rat strains.

    Science.gov (United States)

    Jennings, Elaine M; Okine, Bright N; Olango, Weredeselam M; Roche, Michelle; Finn, David P

    2016-01-01

    Repeated exposure to a homotypic stressor such as forced swimming enhances nociceptive responding in rats. However, the influence of genetic background on this stress-induced hyperalgesia is poorly understood. The aim of the present study was to compare the effects of repeated forced swim stress on nociceptive responding in Sprague-Dawley (SD) rats versus the Wistar Kyoto (WKY) rat strain, a genetic background that is susceptible to stress, negative affect and hyperalgesia. Given the well-documented role of the endocannabinoid system in stress and pain, we investigated associated alterations in endocannabinoid signalling in the dorsal horn of the spinal cord and amygdala. In SD rats, repeated forced swim stress for 10 days was associated with enhanced late phase formalin-evoked nociceptive behaviour, compared with naive, non-stressed SD controls. In contrast, WKY rats exposed to 10 days of swim stress displayed reduced late phase formalin-evoked nociceptive behaviour. Swim stress increased levels of monoacylglycerol lipase (MAGL) mRNA in the ipsilateral side of the dorsal spinal cord of SD rats, an effect not observed in WKY rats. In the amygdala, swim stress reduced anandamide (AEA) levels in the contralateral amygdala of SD rats, but not WKY rats. Additional within-strain differences in levels of CB1 receptor and fatty acid amide hydrolase (FAAH) mRNA and levels of 2-arachidonylglycerol (2-AG) were observed between the ipsilateral and contralateral sides of the dorsal horn and/or amygdala. These data indicate that the effects of repeated stress on inflammatory pain-related behaviour are different in two rat strains that differ with respect to stress responsivity and affective state and implicate the endocannabinoid system in the spinal cord and amygdala in these differences.

  15. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    Science.gov (United States)

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  16. STRESS-STRAIN STATE IN EMBEDMENT OF REINFORCEMENT IN CASE OF REPEATED LOADINGS

    Directory of Open Access Journals (Sweden)

    Mirsayapov Ilshat Talgatovich

    2016-05-01

    Full Text Available The author offer transforming the diagram of ideal elastic-plastic deformations for the description of the stress-strain state of embedment of reinforcement behind a critical inclined crack at repeatedly repeating loadings. The endurance limit of the adhesion between concrete and reinforcement and its corresponding displacements in case of repeated loadings are accepted as the main indicators. This adhesion law is the most appropriate for the description of physical and mechanical phenomena in the contact zone in case of cyclic loading, because it simply and reliably describes the adhesion mechanism and the nature of the deformation, and greatly simplifies the endurance calculations compared to the standard adhesion law. On the basis of this diagram the author obtained the equations for the description of the distribution of pressures and displacements after cyclic loading with account for the development of deformations of cyclic creep of the concrete under the studs of reinforcement.

  17. Lactation-induced reduction in hippocampal neurogenesis is reversed by repeated stress exposure

    OpenAIRE

    Hillerer, K.M.; Neumann, I. D.; Couillard-Despres, S.; Aigner, L.; Slattery, D.A.

    2014-01-01

    The peripartum period is a time of high susceptibility for mood and anxiety disorders, some of which have recently been associated with alterations in hippocampal neurogenesis. Several factors including stress, aging, and, perhaps unexpectedly, lactation have been shown to decrease hippocampal neurogenesis. Intriguingly, lactation is also a time of reduced stress responsivity suggesting that the effect of stress on neurogenic processes may differ during this period. Therefore, the aim of the ...

  18. Systemic and Local Responses to Repeated HL Stress-Induced Retrograde Signaling in Arabidopsis.

    Science.gov (United States)

    Gordon, Matthew J; Carmody, Melanie; Albrecht, Verónica; Pogson, Barry

    2012-01-01

    CHLOROPLASTS OF LEAVES UNDER HIGH LIGHT STRESS INITIATE SIGNALS TO THE NUCLEI OF BOTH EXPOSED AND DISTAL LEAVES IN ORDER TO ACCLIMATE AGAINST THE POTENTIAL THREAT OF OXIDATIVE DAMAGE: a process known as high light systemic acquired acclimation (HL SAA). This study explores the nature of HL SAA, synergistic interactions with other environmental stresses, and the impact of repeated HL stress on the acclimation response of exposed and distal leaves. This necessitated the development of novel experimental systems to investigate the initiation, perception, and response to HL SAA. These systems were used to investigate the HL SAA response by monitoring the induction of mRNA in distal leaves not exposed to the HL stress. Acclimation to HL is induced within minutes and the response is proportionally dependent on the quality and quantity of light. HL SAA treatments in conjunction with variations in temperature and humidity reveal HL SAA is influenced by fluctuations in humidity. These treatments also result in changes in auxin accumulation and auxin-responsive genes. A key question in retrograde signaling is the extent to which transient changes in light intensity result in a "memory" of the event leading to acclimation responses. Repeated exposure to short term HL resulted in acclimation of the exposed tissue and that of emerging and young leaves (but not older leaves) to HL and oxidative stress.

  19. Effect of repeated stress in early childhood on the onset of diabetes mellitus in male Spontaneously Diabetic Torii rats.

    Science.gov (United States)

    Ookawa, Katumasa; Mochizuki, Kazuo; Yokogoshi, Hidehiko

    2008-02-01

    Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated the effect of repeated stress in early childhood on SDT rats fed a high-fat diet, on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a water immersion-restraint stress (WIRS) burden was applied 10 times every other day from 4 weeks of age. The results of the study showed, that the locomotor activity of the young SDT rats was clearly lower than that of the SD rats, and their locomotor activity was inferred to be congenitally low. In addition, the stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired glucose tolerance compared with the rats not receiving stress burden. The locomotor activity of SDT rats is less than that of SD rats, and they SDT rats are thought to have poor at spontaneous energy expenditure. On the other hand, the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in comparison with the SDT rats with no WIRS burden, energy expenditure was increased; this is suggested to influence the onset of diabetes mellitus.

  20. Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    2014-10-01

    Full Text Available Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep-wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by humans, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to either no, mild (10, or severe (100 acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced REM and NREM sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep / wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep / wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders.

  1. Age-related differences in repeated-sprint ability in highly trained youth football players.

    Science.gov (United States)

    Mujika, Inigo; Spencer, Matt; Santisteban, Juanma; Goiriena, Juan Jose; Bishop, David

    2009-12-01

    In this study, we investigated the age-related differences in repeated-sprint ability and blood lactate responses in 134 youth football players. Players from the development programme of a professional club were grouped according to their respective under-age team (U-11 to U-18). Following familiarization, the participants performed a repeated-sprint ability test [6 x 30-m sprints 30 s apart, with active recovery (2.0-2.2 m . s(-1)) between sprints]. The test variables were total time, percent sprint decrement, and post-test peak lactate concentration. Total time improved from the U-11 to U-15 age groups (range 33.15 +/- 1.84 vs. 27.25 +/- 0.82 s), whereas no further significant improvements were evident from U-15 to U-18. No significant differences in percent sprint decrement were reported among groups (range 4.0 +/- 1.0% to 5.5 +/- 2.1%). Post-test peak lactate increased from one age group to the next (range 7.3 +/- 1.8 to 12.6 +/- 1.6 mmol . l(-1)), but remained constant when adjusted for age-related difference in body mass. Peak lactate concentration was moderately correlated with sprint time (r = 0.70, P > 0.001). Our results suggest that performance in repeated-sprint ability improves during maturation of highly trained youth football players, although a plateau occurs from 15 years of age. In contrast to expectations based on previous suggestions, percent sprint decrement during repeated sprints did not deteriorate with age.

  2. Ventral tegmental area dopamine revisited: effects of acute and repeated stress.

    Science.gov (United States)

    Holly, Elizabeth N; Miczek, Klaus A

    2016-01-01

    Aversive events rapidly and potently excite certain dopamine neurons in the ventral tegmental area (VTA), promoting phasic increases in the medial prefrontal cortex and nucleus accumbens. This is in apparent contradiction to a wealth of literature demonstrating that most VTA dopamine neurons are strongly activated by reward and reward-predictive cues while inhibited by aversive stimuli. How can these divergent processes both be mediated by VTA dopamine neurons? The answer may lie within the functional and anatomical heterogeneity of the VTA. We focus on VTA heterogeneity in anatomy, neurochemistry, electrophysiology, and afferent/efferent connectivity. Second, recent evidence for a critical role of VTA dopamine neurons in response to both acute and repeated stress will be discussed. Understanding which dopamine neurons are activated by stress, the neural mechanisms driving the activation, and where these neurons project will provide valuable insight into how stress can promote psychiatric disorders associated with the dopamine system, such as addiction and depression.

  3. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress.

    Science.gov (United States)

    Ren, Qian; Ma, Min; Ishima, Tamaki; Morisseau, Christophe; Yang, Jun; Wagner, Karen M; Zhang, Ji-Chun; Yang, Chun; Yao, Wei; Dong, Chao; Han, Mei; Hammock, Bruce D; Hashimoto, Kenji

    2016-03-29

    Depression is a severe and chronic psychiatric disease, affecting 350 million subjects worldwide. Although multiple antidepressants have been used in the treatment of depressive symptoms, their beneficial effects are limited. The soluble epoxide hydrolase (sEH) plays a key role in the inflammation that is involved in depression. Thus, we examined here the role of sEH in depression. In both inflammation and social defeat stress models of depression, a potent sEH inhibitor, TPPU, displayed rapid antidepressant effects. Expression of sEH protein in the brain from chronically stressed (susceptible) mice was higher than of control mice. Furthermore, expression of sEH protein in postmortem brain samples of patients with psychiatric diseases, including depression, bipolar disorder, and schizophrenia, was higher than controls. This finding suggests that increased sEH levels might be involved in the pathogenesis of certain psychiatric diseases. In support of this hypothesis, pretreatment with TPPU prevented the onset of depression-like behaviors after inflammation or repeated social defeat stress. Moreover, sEH KO mice did not show depression-like behavior after repeated social defeat stress, suggesting stress resilience. The sEH KO mice showed increased brain-derived neurotrophic factor (BDNF) and phosphorylation of its receptor TrkB in the prefrontal cortex, hippocampus, but not nucleus accumbens, suggesting that increased BDNF-TrkB signaling in the prefrontal cortex and hippocampus confer stress resilience. All of these findings suggest that sEH plays a key role in the pathophysiology of depression, and that epoxy fatty acids, their mimics, as well as sEH inhibitors could be potential therapeutic or prophylactic drugs for depression.

  4. Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.

    Science.gov (United States)

    Sotomayor-Zárate, Ramón; Abarca, Jorge; Araya, Katherine A; Renard, Georgina M; Andrés, María E; Gysling, Katia

    2015-11-01

    A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Repeated trauma exposure does not impair distress reduction during imaginal exposure for posttraumatic stress disorder.

    Science.gov (United States)

    Jerud, Alissa B; Farach, Frank J; Bedard-Gilligan, Michele; Smith, Hillary; Zoellner, Lori A; Feeny, Norah C

    2017-08-01

    Based on experimental research on threat extinction, individuals exposed to repeated traumatic events may have impaired outcome in exposure therapy compared to those who have experienced a single trauma (Lang & McTeague, ). This study examined whether repeated trauma exposure predicts smaller changes in self-reported distress during imaginal exposure and worse outcomes for patients with posttraumatic stress disorder (PTSD). Adults (N = 116) with chronic PTSD received up to 10 sessions of prolonged exposure (PE) therapy. Trauma exposure was assessed via interview and number of traumatic events were summed for each participant. To examine reductions in distress during treatment, mean and peak values of distress during imaginal exposure were calculated for the first imaginal session (initial distress activation) and subsequent sessions (between-session change in distress). Change in PTSD symptoms from pre- to posttreatment and follow-up provided an additional index of outcome. In-session distress during imaginal exposure decreased over the course of treatment. PTSD symptoms also decreased over treatment, with gains being maintained through follow-up. Repeated trauma exposure was not significantly correlated with initial distress activation. Additionally, linear mixed-model analyses showed no significant association between repeated trauma exposure and between-session change in distress or PTSD symptoms. Contrary to recent speculation, repeated trauma exposure did not predict less change in self-reported distress during imaginal exposure or worse PTSD outcomes. The bench-to-bedside linkage of threat extinction to exposure therapy is discussed, noting strengths and weaknesses. Patients with repeated trauma exposure show reductions in distress with exposure treatment and benefit from PE as much as patients with single-exposure trauma histories. © 2016 Wiley Periodicals, Inc.

  6. B-type natriuretic peptide (BNP serum levels in rats after forced repeated swimming stress

    Directory of Open Access Journals (Sweden)

    Almira Hadžovic-Džuvo

    2011-02-01

    Full Text Available Aim To estimate the effects of forced repeated swimming stress on BNP serum levels in rats. Methods Adult male Wistar rats weighting between 280-330 g were divided into two groups: control group (n =8 and stress group (n =8. Rats in the stress group were exposed to forced swimming stress daily, for 7 days. The rats were forced to swim in plastic tanks (90 cm wide, 120 cm deep containing tap water (temperature ca. 25°C. The depth of water was 40 cm. Duration of each swimming session progressively increased from 10 minutes on the irst day to 40 minutes on days 6 and 7. Rats were sacriiced and blood was drawn from abdominal aorta for BNP analysis immediately after the last swimming session. B-type natriuretic serum level was determined by ELISA method using RAT BNP-32 kit (Phoenix Pharmaceutical Inc.. Results There was no statistically signiicant difference between mean BNP serum level in the stress group after the swimming period (0.81±0.14 ng/ml as compared to the unstressed group of rats (0.8 ±0.08ng/ml. After the swimming period mean body weight slightly decreased in the stress group in comparison with values before stress period (296.3 g vs.272.8 g, but this difference was not statistically signiicant. The stress period had no inluence on food intake in the stress rat group. Conclusion The workload consisting of 40-minutes long swimming session is not suficient to provoke BNP release from myocardium in rats.

  7. Activation of physiological stress responses by a natural reward: Novel vs. repeated sucrose intake.

    Science.gov (United States)

    Egan, Ann E; Ulrich-Lai, Yvonne M

    2015-10-15

    Pharmacological rewards, such as drugs of abuse, evoke physiological stress responses, including increased heart rate and blood pressure, and activation of the hypothalamic-pituitary-adrenal (HPA) axis. It is not clear to what extent the natural reward of palatable foods elicits similar physiological responses. In order to address this question, HPA axis hormones, heart rate, blood pressure and brain pCREB immunolabeling were assessed following novel and repeated sucrose exposure. Briefly, adult, male rats with ad libitum food and water were given either a single (day 1) or repeated (twice-daily for 14 days) brief (up to 30 min) exposure to a second drink bottle containing 4 ml of 30% sucrose drink vs. water (as a control for bottle presentation). Sucrose-fed rats drank more than water-fed on all days of exposure, as expected. On day 1 of exposure, heart rate, blood pressure, plasma corticosterone, and locomotion were markedly increased by presentation of the second drink bottle regardless of drink type. After repeated exposure (day 14), these responses habituated to similar extents regardless of drink type and pCREB immunolabeling in the hypothalamic paraventricular nucleus (PVN) also did not vary with drink type, whereas basolateral amygdala pCREB was increased by sucrose intake. Taken together, these data suggest that while sucrose is highly palatable, physiological stress responses were evoked principally by the drink presentation itself (e.g., an unfamiliar intervention by the investigators), as opposed to the palatability of the offered drink.

  8. Response of the Hypothalamic-Pituitary-Adrenal System to Repeated Moderate Psychoemotional Stress Exposure Is Associated with Behavioral Parameters.

    Science.gov (United States)

    Goncharova, N D; Chigarova, O A; Oganyan, T E

    2017-05-01

    Individual features of the response of the hypothalamic-pituitary-adrenal axis (HPAA) to repeated moderate stress exposure (daily 2-h restraint stress for 10 days) was studied in young female rhesus monkeys with healthy normal behavior and combined group of female rhesus monkeys with abnormal depression-like and anxious behavior. No between-group differences in the response of ACTH and cortisol were found on day 1. On day 10, a rapid and less pronounced increase in ACTH secretion was observed in all animals in comparison with day 1. Analysis of between-group differences in HPAA response showed higher increase in ACTH level and lower increase in cortisol concentration in animals with depression-like and anxious behavior. These changes were similar to the previously described differences in the response of the adenohypophysis and adrenal cortex to acute restraint stress in old monkeys with similar behavior. Thus, individuals with depression-like and anxious behavior demonstrate impaired stress-induced reactivity of HPAA as early as in young age.

  9. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  10. Individual differences and repeatability in vocal production: stress-induced calling exposes a songbird's personality

    Science.gov (United States)

    Guillette, Lauren M.; Sturdy, Christopher B.

    2011-11-01

    Recent research in songbirds has demonstrated that male singing behavior varies systematically with personality traits such as exploration and risk taking. Here we examine whether the production of bird calls, in addition to bird songs, is repeatable and related to exploratory behavior, using the black-capped chickadee ( Poecile atricapillus) as a model. We assessed the exploratory behavior of individual birds in a novel environment task. We then recorded the vocalizations and accompanying motor behavior of both male and female chickadees, over the course of several days, in two different contexts: a control condition with no playback and a stressful condition where chick-a-dee mobbing calls were played to individual birds. We found that several vocalizations and behaviors were repeatable within both a control and a stressful context, and across contexts. While there was no relationship between vocal output and exploratory behavior in the control context, production of alarm and chick-a-dee calls in the stressful condition was positively associated with exploratory behavior. These findings are important because they show that bird calls, in addition to bird song, are an aspect of personality, in that calls are consistent both within and across contexts, and covary with other personality measures (exploration).

  11. A Familial Factor Independent of CAG Repeat Length Influences Age at Onset of Machado-Joseph Disease

    OpenAIRE

    DeStefano, Anita L.; Cupples, L. Adrienne; Maciel, Patricia; Gaspar, Claudia; Radvany, Joao; Dawson, David M.; Sudarsky, Lewis; Corwin, Lee; Coutinho, Paula; MacLeod, Patrick; Sequeiros, Jorge; Rouleau, Guy A.; Farrer, Lindsay A.

    1996-01-01

    Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, t...

  12. Repeated psychosocial stress at night, but not day, affects the central molecular clock.

    Science.gov (United States)

    Bartlang, Manuela S; Savelyev, Sergey A; Johansson, Anne-Sofie; Reber, Stefan O; Helfrich-Förster, Charlotte; Lundkvist, Gabriella B S

    2014-11-01

    We have recently demonstrated that the outcome of repeated social defeat (SD) on behavior, physiology and immunology is more negative when applied during the dark/active phase as compared with the light/inactive phase of male C57BL/6 mice. Here, we investigated the effects of the same stress paradigm, which combines a psychosocial and novelty stressor, on the circadian clock in transgenic PERIOD2::LUCIFERASE (PER2::LUC) and wildtype (WT) mice by subjecting them to repeated SD, either in the early light phase (social defeat light = SDL) or in the early dark phase (social defeat dark = SDD) across 19 days. The PER2::LUC rhythms and clock gene mRNA expression were analyzed in the suprachiasmatic nucleus (SCN) and the adrenal gland, and PER2 protein expression in the SCN was assessed. SDD mice showed increased PER2::LUC rhythm amplitude in the SCN, reduced Per2 and Cryptochrome1 mRNA expression in the adrenal gland, and increased PER2 protein expression in the posterior part of the SCN compared with single-housed control (SHC) and SDL mice. In contrast, PER2::LUC rhythms in the SCN of SDL mice were not affected. However, SDL mice exhibited a 2-hour phase advance of the PER2::LUC rhythm in the adrenal gland compared to SHC mice. Furthermore, plasma levels of brain-derived neurotrophic factor (BDNF) and BDNF mRNA in the SCN were elevated in SDL mice. Taken together, these results show that the SCN molecular rhythmicity is affected by repeated SDD, but not SDL, while the adrenal peripheral clock is influenced mainly by SDL. The observed increase in BDNF in the SDL group may act to protect against the negative consequences of repeated psychosocial stress.

  13. Repeat retail clinic visits: impact of insurance coverage and age of patient.

    Science.gov (United States)

    Angstman, Kurt B; Bernard, Matthew E; Rohrer, James E; Garrison, Gregory M; Maclaughlin, Kathy L

    2012-12-01

    As retail clinics provide a less costly alternative for health care, it would be reasonable to expect an increase in multiple (repeat) retail visits by those patients who may have expenses for receiving primary care. If costs were not a significant factor, then repeat visits should not be significantly different between these patients and those with coverage for primary care visits. The hypothesis for this study was that patients with the potential for out-of-pocket expenses would have a higher frequency of repeat retail clinic visits within 180 days compared to those with primary care coverage. A retrospective chart review was conducted of 5703 patients utilizing a retail clinic in Rochester, Minnesota from January 1, 2009 through June 30, 2009. The first visit to the retail clinic was considered the index visit and the chart was reviewed for repeat retail clinic visits within the next 180 days. Using a multiple logistic regression model, the odds of a pediatric patient (N=2344) having a repeat retail visit within 180 days of the index visit were not significantly impacted by insurance coverage (P=0.4209). Of the 3359 adult patients, those with unknown coverage had a 25.6% higher odds ratio of repeat retail clinic visits than those with insurance coverage (odds ratio 1.2557, confidence interval 1.0421-1.5131). This study suggested that when cost is an issue, the adult patient may favor retail clinics for episodic, low-acuity health care. In contrast, the pediatric population did not, suggesting that other factors, such as convenience, may play more of a role in the choice of episodic health care for this age group.

  14. Hsp72 is present in plasma from Holstein-Friesian dairy cattle, and the concentration level is repeatable across days and age classes.

    Science.gov (United States)

    Kristensen, Torsten Nygaard; Løvendahl, Peter; Berg, Peer; Loeschcke, Volker

    2004-01-01

    Although heat shock proteins (Hsps) are primarily considered as being intracellular, this study identified the presence of Hsp72 in plasma from female Holstein-Friesian dairy cattle. Plasma samples were collected from the same animals at different ages and on different days after calving and accordingly divided into 5 age classes. The age classes were calves less than 235 days of age, young heifers between 235 and 305 days of age, older heifers between 305 and 560 days of age, cows early in lactation, and cows later in lactation. For a subsample of animals within each age class, replicate plasma samples were collected from 1 to 7 days apart to test whether the Hsp72 concentration levels are repeatable on this shorter timescale. Hsp72 was observed in plasma samples from animals of all 5 age classes. For animals with blood samples taken a few days apart, the repeatability (within age class) of the Hsp72 concentration was 0.52 +/- 0.06. Age and days from calving significantly affected the Hsp72 concentration level. The highest Hsp72 level was observed in older heifers (305-560 days of age). The repeatability of Hsp72 concentrations across age classes within animal was 0.22 +/- 0.06. High environmental sensitivity and negative genetic associations between production and health traits in this high-producing breed have been documented earlier. Hsp72 is believed to be strictly stress inducible, and the finding of Hsp72 in plasma indicates that even apparently healthy individuals may experience extrinsic or intrinsic stress (or both).

  15. Effects of repeated psychological stress training on the spectrum of serum protein expression in special troops

    Directory of Open Access Journals (Sweden)

    Li ZHANG

    2011-10-01

    Full Text Available Objective To investigate the effects of repeated psychological stress training on the serum protein expression in soldiers under mental stress.Methods Ninety-six male commando soldiers were randomly assigned into the common psychological training group,the circulation psychological training group and the control group(32 each.After a 4-week training,all the soldiers were instructed to attend an one-day high-intensity simulated anti-riot exercise,and 3 days later attended another unannounced high-intensity simulated anti-riot exercise.Blood samples were collected from all the soldiers within 4 hours after each exercise,and the changes in serum protein expression were determined and statistically analyzed by using surface-enhanced laser desorption/ionization time of flight mass spectrometry(SELDI-TOF-MS combined with ProteinChip technology.Results The variance analysis showed that significant differences existed among the three groups(P < 0.05 in the relative contents of proteins with M/Z values of 6417.8,9134.2,15171.9 and 14972.7D after the first anti-riot exercise,and the relative contents of all the above mentioned proteins increased in the circulatory psychological training group;meanwhile,markedly increasing trends of the relative contents of all the proteins were observed in the three groups after the second anti-riot exercise(P < 0.05,and in control group the relative contents of the 4 above mentioned proteins were significantly higher than those after the first anti-riot exercise.Conclusion Psychological training may up-regulate the expression of serum proteins that are down-regulated after stress,and the repeated high-intensity mental training can rapidly improve the soldiers’ ability to counteract stress.

  16. Synaptic Impairment in Layer 1 of the Prefrontal Cortex Induced by Repeated Stress During Adolescence is Reversed in Adulthood

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Dagnino-Subiabre, Alexies; Muñoz Carvajal, Pablo

    2015-01-01

    Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC) slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory post-synaptic potential (fEPSP) in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD). Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period. PMID:26617490

  17. Perfectionism Affects Blood Pressure in Response to Repeated Exposure to Stress.

    Science.gov (United States)

    Albert, Phebe; Rice, Kenneth G; Caffee, Lauren

    2016-04-01

    This pilot study examined the effects of perfectionism on blood pressure (BP) in response to repeated exposure to mental arithmetic stressors. College students (N = 30) in a laboratory setting were administered a series of challenging mathematical tasks. BP was measured at baseline and after each task. Multilevel modelling analyses revealed that BP tended to decline over the course of the mathematical tasks. However, higher levels of performance standards predicted relatively stable levels of systolic BP, whereas moderate and lower levels of standards predicted declines in systolic BP. Higher levels of self-critical perfectionism predicted generally sustained levels of diastolic BP, with moderate and low self-criticism predicting declines in diastolic BP during the repeated stressors. These preliminary results suggest that students with higher levels of perfectionism may be at risk for physiological problems associated with stress reactivity, perhaps especially so in situations in which they experience persistent stress. Although results were qualified by a relatively small sample size, effects were statistically significant and supported the importance of examining the short-term and long-term implications of the effects of perfectionism on cardiovascular function and the different implications of elevations in systolic and diastolic BP.

  18. Aerobic capacity in wild satin bowerbirds: repeatability and effects of age, sex and condition.

    Science.gov (United States)

    Chappell, Mark A; Savard, Jean-Francois; Siani, Jennifer; Coleman, Seth W; Keagy, Jason; Borgia, Gerald

    2011-10-01

    Individual variation in aerobic capacity has been extensively studied, especially with respect to condition, maturity or pathogen infection, and to gain insights into mechanistic foundations of performance. However, its relationship to mate competition is less well understood, particularly for animals in natural habitats. We examined aerobic capacity [maximum rate of O2 consumption (VO2,max) in forced exercise] in wild satin bowerbirds, an Australian passerine with a non-resource based mating system and strong intermale sexual competition. We tested for repeatability of mass and VO2,max, differences among age and sex classes, and effects of several condition indices. In adult males, we examined interactions between aerobic performance and bower ownership (required for male mating success). There was significant repeatability of mass and VO2,max within and between years, but between-year repeatability was lower than within-year repeatability. VO2,max varied with an overall scaling to mass(0.791), but most variance in VO2,max was not explained by mass. Indicators of condition (tarsus and wing length asymmetry, the ratio of tarsus length to mass) were not correlated to VO2,max. Ectoparasite counts were weakly correlated to VO2,max across all age-sex classes but not within any class. Adult males, the cohort with the most intense levels of mating competition, had higher VO2,max than juvenile birds or adult females. However, there was no difference between the VO2,max of bower-owning males and that of males not known to hold bowers. Thus one major factor determining male reproductive success was not correlated to aerobic performance.

  19. How integrated are behavioral and endocrine stress response traits? A repeated measures approach to testing the stress-coping style model.

    Science.gov (United States)

    Boulton, Kay; Couto, Elsa; Grimmer, Andrew J; Earley, Ryan L; Canario, Adelino V M; Wilson, Alastair J; Walling, Craig A

    2015-02-01

    It is widely expected that physiological and behavioral stress responses will be integrated within divergent stress-coping styles (SCS) and that these may represent opposite ends of a continuously varying reactive-proactive axis. If such a model is valid, then stress response traits should be repeatable and physiological and behavioral responses should also change in an integrated manner along a major axis of among-individual variation. While there is some evidence of association between endocrine and behavioral stress response traits, few studies incorporate repeated observations of both. To test this model, we use a multivariate, repeated measures approach in a captive-bred population of Xiphophorus birchmanni. We quantify among-individual variation in behavioral stress response to an open field trial (OFT) with simulated predator attack (SPA) and measure waterborne steroid hormone levels (cortisol, 11-ketotestosterone) before and after exposure. Under the mild stress stimulus (OFT), (multivariate) behavioral variation among individuals was consistent with a strong axis of personality (shy-bold) or coping style (reactive-proactive) variation. However, behavioral responses to a moderate stressor (SPA) were less repeatable, and robust statistical support for repeatable endocrine state over the full sampling period was limited to 11-ketotestosterone. Although post hoc analysis suggested cortisol expression was repeatable over short time periods, qualitative relationships between behavior and glucocorticoid levels were counter to our a priori expectations. Thus, while our results clearly show among-individual differences in behavioral and endocrine traits associated with stress response, the correlation structure between these is not consistent with a simple proactive-reactive axis of integrated stress-coping style. Additionally, the low repeatability of cortisol suggests caution is warranted if single observations (or indeed repeat measures over short sampling

  20. Repeated exposure to heat stress results in a diaphragm phenotype that resists ventilator-induced diaphragm dysfunction.

    Science.gov (United States)

    Yoshihara, Toshinori; Ichinoseki-Sekine, Noriko; Kakigi, Ryo; Tsuzuki, Takamasa; Sugiura, Takao; Powers, Scott K; Naito, Hisashi

    2015-11-01

    Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.

  1. Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.

    Science.gov (United States)

    Imrich, Richard; Tibenska, Elena; Koska, Juraj; Ksinantova, Lucia; Kvetnansky, Richard; Bergendiova-Sedlackova, Katarina; Blazicek, Pavol; Vigas, Milan

    2004-06-01

    Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.

  2. Mitochondrial Inverted Repeats Strongly Correlate with Lifespan: mtDNA Inversions and Aging

    Science.gov (United States)

    Yang, Jiang-Nan; Seluanov, Andrei; Gorbunova, Vera

    2013-01-01

    Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson’s disease, and Huntington’s disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA) deletions caused by direct repeats (DRs) are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson’s r = −0.22, p<0.002; Spearman’s ρ = −0.12, p = 0.1) correlation with maximum lifespan (MLS). Here we report a stronger correlation (Pearson’s r = −0.55, p<10–16; Spearman’s ρ = −0.52, p<10–14) between mitochondrial inverted repeats (IRs) and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects. PMID:24069185

  3. Mitochondrial inverted repeats strongly correlate with lifespan: mtDNA inversions and aging.

    Directory of Open Access Journals (Sweden)

    Jiang-Nan Yang

    Full Text Available Mitochondrial defects are implicated in aging and in a multitude of age-related diseases, such as cancer, heart failure, Parkinson's disease, and Huntington's disease. However, it is still unclear how mitochondrial defects arise under normal physiological conditions. Mitochondrial DNA (mtDNA deletions caused by direct repeats (DRs are implicated in the formation of mitochondrial defects, however, mitochondrial DRs show relatively weak (Pearson's r = -0.22, p<0.002; Spearman's ρ = -0.12, p = 0.1 correlation with maximum lifespan (MLS. Here we report a stronger correlation (Pearson's r = -0.55, p<10(-16; Spearman's ρ = -0.52, p<10(-14 between mitochondrial inverted repeats (IRs and lifespan across 202 species of mammals. We show that, in wild type mice under normal conditions, IRs cause inversions, which arise by replication-dependent mechanism. The inversions accumulate with age in the brain and heart. Our data suggest that IR-mediated inversions are more mutagenic than DR-mediated deletions in mtDNA, and impose stronger constraint on lifespan. Our study identifies IR-induced mitochondrial genome instability during mtDNA replication as a potential cause for mitochondrial defects.

  4. Metabolic rate variation over adult lifetime in the butterfly Vanessa cardui (Nymphalidae: Nymphalinae): aging, feeding, and repeatability.

    Science.gov (United States)

    Woods, William A; Wood, C A L; Ebersole, John; Stevenson, R D

    2010-01-01

    Questions about the adaptive importance of metabolic rate can be approached only when measurements of differences between individuals are repeatable. We made daily measurements of CO(2) production, body mass, and food uptake over the adult life span of unmated Vanessa cardui kept under constant environmental conditions in both fed and unfed treatments. Mass and CO(2) production generally declined with age in both treatments, though with much day-to-day variability in the fed treatment. For the full samples, metabolic rate was repeatable for the unfed treatment (repeatability r = 0.60) but not for the fed treatment (r = 0.03). Differences between fed and unfed individuals of the same age range were repeatable for the unfed treatment (r = 0.39) but not for the fed treatment (r = -0.20). Removing age effects on CO(2) production yielded still higher repeatability in the unfed treatment (r = 0.83), though not in fed butterflies of the same age range (r = -0.02). However, repeatability of CO(2) production of fed butterflies increased sharply with age, rising to 0.82 for butterflies age 8-10 d. Although food uptake mass was repeatable (r = 0.52), feeding history explained little variation in CO(2) production. We conclude that for V. cardui and possibly for other insects of similar feeding habit, variation in metabolic rate between individuals is best represented by measurements of unfed individuals of the same age or of older fed individuals.

  5. Oxidative stress, mitochondrial dysfunction and the mitochondria theory of aging.

    Science.gov (United States)

    Kong, Yahui; Trabucco, Sally E; Zhang, Hong

    2014-01-01

    Aging is characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-associated diseases and death. One potential cause of aging is the progressive accumulation of dysfunctional mitochondria and oxidative damage with age. Considerable efforts have been made in our understanding of the role of mitochondrial dysfunction and oxidative stress in aging and age-associated diseases. This chapter outlines the interplay between oxidative stress and mitochondrial dysfunction, and discusses their impact on senescence, cell death, stem cell function, age-associated diseases and longevity.

  6. Impact of repeated stress on traumatic brain injury-induced mitochondrial electron transport chain expression and behavioral responses in rats

    Directory of Open Access Journals (Sweden)

    Guoqiang eXing

    2013-12-01

    Full Text Available A significant proportion of the military personnel returning from Iraq and Afghanistan conflicts have suffered from both mild traumatic brain injury (mTBI and post-traumatic stress disorder (PTSD. The mechanisms are unknown. We used a rat model of repeated stress and mTBI to examine brain activity and behavioral function. Adult male Sprague-Dawley rats were divided into 4 groups: Naïve; 3 days repeated tail-shock stress; lateral fluid percussion mTBI; and repeated stress followed by mTBI (S-mTBI. Open field activity, sensorimotor responses, and acoustic startle responses were measured after mTBI. The protein expression of mitochondrial electron transport chain (ETC complex subunits (CI-V and pyruvate dehydrogenase (PDHE1α1 were determined in 4 brain regions at day 7 post mTBI. Compared to Naïves, repeated stress decreased horizontal activity; repeated stress and mTBI both decreased vertical activity; and the mTBI and S-mTBI groups were impaired in sensorimotor and acoustic startle responses. Repeated stress significantly increased CI, CII, and CIII protein levels in the prefrontal cortex (PFC, but decreased PDHE1α1 protein in the PFC and cerebellum, and decreased CIV protein in the hippocampus. The mTBI treatment decreased CV protein levels in the ipsilateral hippocampus. The S-mTBI treatment resulted in increased CII, CIII, CIV, and CV protein levels in the PFC, increased CI level in the cerebellum, and increased CIII and CV levels in the cerebral cortex, but decreased CI, CII, CIV, and PDHE1α1 protein levels in the hippocampus. Thus, repeated stress or mTBI alone differentially altered ETC expression in heterogeneous brain regions. Repeated stress followed by mTBI had synergistic effects on brain ETC expression, and resulted in more severe behavioral deficits. These results suggest that repeated stress could have contributed to the high incidence of long-term neurologic and neuropsychiatric morbidity in military personnel with or without

  7. Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

    Directory of Open Access Journals (Sweden)

    Radoja Sasa

    2007-11-01

    Full Text Available Abstract Background The phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity. Presentation of the hypothesis This paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections. Testing the hypothesis The proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells of the cold-exposed group would be compared to

  8. Repeatability of contrast sensitivity testing in patients with age-related macular degeneration, glaucoma, and cataract

    Directory of Open Access Journals (Sweden)

    Selcuk Kara

    Full Text Available ABSTRACT Purpose: To analyze the intrasession and intersession repeatability of contrast sensitivity (CS measurements in patients with glaucoma, cataract, or age-related macular degeneration (AMD and healthy controls. Methods: CS measurements were performed using the OPTEC-Functional Vision Analyzer (FVA, which uses a standardized and closed (view-in system. Measurements for patients with glaucoma, cataract, or AMD and healthy controls were repeated within 30 minutes (intrasession and during two sessions (intersession, separated by one week to one month. Test-retest reliability and correlation were measured using the intraclass correlation coefficient (ICC and coefficient of repeatability (COR. Results: Ninety subjects (90 eyes with visual acuity of 0.17 logMAR or higher in the cataract group or 0.00 logMAR in the other groups were included. During the first session, the ICC values were 0.87, 0.90, 0.76, and 0.69, and COR values were 0.24, 0.20, 0.38, and 0.25 for the control, glaucoma, cataract, and AMD groups, respectively. The reliability scores significantly improved during the second session, except in the glaucoma group. There was an acceptable floor effect and no ceiling effect at higher frequencies in the glaucoma and AMD groups. Conclusion: In subjects with good visual acuity, the FVA system is useful for evaluating CS and demonstrates good repeatability, as shown by ICC and COR. Because there is no ceiling effect, this system is beneficial for evaluation of early changes in CS, particularly in patients with glaucoma or AMD.

  9. Learning during middle age: A resistance to stress?

    OpenAIRE

    Hodes, Georgia E; Shors, Tracey J.

    2006-01-01

    Acute stressful experience enhances subsequent learning in males and impairs learning in females. These sex differences emerge soon after puberty in adulthood. Whether these opposite effects of stress on learning extend into older age is unknown. To examine this, young adult (2–3 months) and middle aged (17–18 months) Fischer 344 rats of both sexes were exposed to an acute stress or of brief tail shocks and trained 24 h later with classical eyeblink conditioning using a trace paradigm. Wherea...

  10. Relationship among Repeated Sprint Ability, Chronological Age and Puberty in young soccer players.

    Science.gov (United States)

    Perroni, Fabrizio; Pintus, Antonio; Frandino, Mattia; Guidetti, Laura; Baldari, Carlo

    2016-01-20

    The aim of this study was to analyzed the relationship of Repeated Sprinting Ability (RSA) with chronological age and puberty in 100 young soccer players (Age: 13 ± 3 yr - 160 ± 33 month-; High: 159 ± 16 cm, Weight: 49.7 ± 14.1 kg; BMI 19.2 ± 2.5 kg/m) grouped on "Pulcini" (9 - 10 yrs), "Esordienti" (11 - 12 yrs), "Giovanissimi" (13 - 14 yrs), "Allievi" (15 - 16 yrs) and "Juniores" (> 17 yrs) categories. Anthropometric (Weight, Height, BMI), RSA (7x30 m sprint with 25s active rest: Total Time -TT, the lowest sprinting time (LST) and the fatigue index percentage -%IF), and Development (Self-Administered Rating Scale for pubertal development - PDS; Puberty) parameters were measured. ANOVA among categories was applied to asses differences (pinjury and overtraining during the different phases of growth and maturation.

  11. Stress and Subjective Age: Those With Greater Financial Stress Look Older.

    Science.gov (United States)

    Agrigoroaei, Stefan; Lee-Attardo, Angela; Lachman, Margie E

    2016-07-14

    Subjective indicators of age add to our understanding of the aging process beyond the role of chronological age. We examined whether financial stress contributes to subjective age as rated by others and the self. The participants (N = 228), aged 26-75, were from a Boston area satellite of the Midlife in the United States (MIDUS) longitudinal study. Participants reported how old they felt and how old they thought they looked, and observers assessed the participants' age based on photographs (other-look age), at two occasions, an average of 10 years apart. Financial stress was measured at Time 1. Controlling for income, general stress, health, and attractiveness, participants who reported higher levels of financial stress were perceived as older than their actual age to a greater extent and showed larger increases in other-look age over time. We consider the results on accelerated aging of appearance with regard to their implications for interpersonal interactions and in relation to health.

  12. Oxidative Stress, Mitochondrial Dysfunction, and Aging

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    Hang Cui

    2012-01-01

    Full Text Available Aging is an intricate phenomenon characterized by progressive decline in physiological functions and increase in mortality that is often accompanied by many pathological diseases. Although aging is almost universally conserved among all organisms, the underlying molecular mechanisms of aging remain largely elusive. Many theories of aging have been proposed, including the free-radical and mitochondrial theories of aging. Both theories speculate that cumulative damage to mitochondria and mitochondrial DNA (mtDNA caused by reactive oxygen species (ROS is one of the causes of aging. Oxidative damage affects replication and transcription of mtDNA and results in a decline in mitochondrial function which in turn leads to enhanced ROS production and further damage to mtDNA. In this paper, we will present the current understanding of the interplay between ROS and mitochondria and will discuss their potential impact on aging and age-related diseases.

  13. The number of CAG repeats within the normal allele does not influence the age of onset in Huntington's disease.

    Science.gov (United States)

    Klempíř, Jiří; Zidovská, Jana; Stochl, Jan; Ing, Věra Kebrdlová; Uhrová, Tereza; Roth, Jan

    2011-01-01

    Huntington's disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved.

  14. Dynamic damage and stress-strain relations of ultra-high performance cementitious composites subjected to repeated impact

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Ultra-high performance cementitious composites (UHPCC) were prepared by replacing 60% of cement with ultra-fine industrial waste powders.The dynamic damage and compressive stress-strain relations of UHPCC were studied using split Hopkinson pressure bar (SHPB).The damage of UHPCC subjected to repeated impact was measured by the ultrasonic pulse velocity method.Results show that the dynamic damage of UHPCC increases linearly with impact times and the abilities of repeated impact resistance of UHPCC are improved with increasing fiber volume fraction.The stress waves on impact were recorded and the average stress,strain and strain rate of UHPCC were calculated based on the wave propagation theory.The effects of strain rate,fibers volume fraction and impact times on the stress-strain relations of UHPCC were studied.Results show that the peak stress and elastic modulus decrease while the strain rate and peak strain increase gradually with increasing impact times.

  15. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

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    Torres I.L.S.

    2001-01-01

    Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  16. Stress and Its Consequences from Prenatal Period to Older Ages

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    Nilay Pekel Uludagli

    2017-06-01

    Full Text Available Human life includes numerous developmental changes starting from the mother's womb to old ages. Both age related physical, cognitive, and emotional changes and social roles that are expected to be fulfilled at every age period require individual to adapt new conditions. Even if these new conditions are sometimes desirable, they lead individuals to feel stress. Although there are a large number of studies about stress in the relevant literature, they either approached stress pathologically or focused on specific age groups; how stress affects an individual across the life span was not addressed holistically. This review examined the important life events that are experienced respectively in the infancy, childhood, adolescence, adulthood, and older ages and the effects of these life events on the individuals' health from the life span perspective. Accordingly, each individual's conditions such as the amount of social support, living in a disadvantaged district, healthy life habits, and coping skills determine to what extent the individual experiences stress. The stress that the individual experiences with varying degrees in each age period may affect his/her physical and psychological health negatively. Although developmental stress is inevitable, having positive and supportive social relations helps coping with stress effectively. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(2.000: 189-208

  17. Chronic pain, perceived stress, and cellular aging: an exploratory study

    Directory of Open Access Journals (Sweden)

    Sibille Kimberly T

    2012-02-01

    Full Text Available Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL, a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of TL as a biological marker reflecting the burden of chronic pain and psychosocial stress has not yet been explored. Findings The relationship between chronic pain, stress, and TL was analyzed in 36 ethnically diverse, older adults, half of whom reported no chronic pain and the other half had chronic knee osteoarthritis (OA pain. Subjects completed a physical exam, radiographs, health history, and psychosocial questionnaires. Blood samples were collected and TL was measured by quantitative polymerase chain reaction (qPCR. Four groups were identified characterized by pain status and the Perceived Stress Scale scores: 1 no pain/low stress, 2 no pain/high stress, chronic pain/low stress, and 4 chronic pain/high stress. TL differed between the pain/stress groups (p = 0.01, controlling for relevant covariates. Specifically, the chronic pain/high stress group had significantly shorter TL compared to the no pain/low stress group. Age was negatively correlated with TL, particularly in the chronic pain/high stress group (p = 0.03. Conclusions Although preliminary in nature and based on a modest sample size, these findings indicate that cellular aging may be more pronounced in older adults experiencing high levels of perceived stress and chronic pain.

  18. [Molecular mechanism of accelerating ageing by oxidative stress].

    Science.gov (United States)

    Yoshikawa, Toshikazu; Naito, Yuji

    2009-07-01

    Reactive oxygen species are important for many life sustaining processes of cells and tissues, but they can also induce cell damage and death. If their production and levels within cells are not effectively controlled, then the detrimental effects of oxidative stress can accumulate. Oxidative stress is widely thought to underpin many ageing processes, and the oxidative stress theory of ageing is one of the most widely acknowledged theories of ageing. As well as being the major source of reactive oxygen species, mitochondria are also a major site of oxidative damage. The purpose of this review is a concise and current review of the role of oxidative stress in ageing process. Emphasis is placed upon the roles of mitochondrial proton leak, the uncoupling proteins, and the anti-ageing effects of caloric restriction.

  19. Water aging reverses residual stresses in hydrophilic dental composites.

    Science.gov (United States)

    Park, J W; Ferracane, J L

    2014-02-01

    Dental composites develop residual stresses during polymerization due to shrinkage. These stresses may change with time because of relaxation and water sorption in the oral environment. This phenomenon is likely dependent on the composition of the materials, specifically their hydrophilic characteristics, and could result in deleterious stresses on restorative materials and tooth structure. The purpose of this experiment was to use the thin ring-slitting method to compare the residual stress generated within composite materials of varying hydrophilicity when aged in wet and dry conditions after polymerization. Water sorption, solubility, elastic modulus, and residual stresses were measured in 6 commercial composites/cements aged in water and dry conditions. The self-adhesive resin cement showed the highest water sorption and solubility. All composites showed initial residual contraction stresses, which were maintained when aged dry. Residual stresses in 2 of the self-adhesive cements and the polyacid-modified composite aged in wet conditions resulted in a net expansion. This experiment verified that residual shrinkage stresses in dental composites can be reversed during aging in water, resulting in a net expansion, with the effect directly related to their hydrophilic properties.

  20. [Stress in school-age children].

    Science.gov (United States)

    Plourde, R G

    1994-10-01

    In April 1988, following preliminary research, Notre Dame Elementary School in Edmunston, N.B. initiated a pilot project entitled Management of Children's Stress. Using a three-dimensional process, parents, teachers and students collaborated to empower all students enrolled at the school to effectively manage their day-to-day stress. To prepare, the children, parents and teachers participated in nine- and 15-hour education sessions, respectively. Various techniques, including deep breathing exercises, stretching, relaxation techniques and listening to music, were considered. Visualization, maximizing the mind's potential to envision relaxing images, became the preferred technique. In addition to complementing other relaxation techniques used by the children, visualization facilitated their learning; developed and improved their concentration, motivation and self-confidence; gave them a positive self-image; and reduced health problems. The project has surpassed all expectations. In March 1993, it became part of a Quality of Life Education Project at the school.

  1. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging

    Directory of Open Access Journals (Sweden)

    Heather M Buechel

    2014-02-01

    Full Text Available Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/ stress hormone/ allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation, and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 mo. and aged (21 mo. male F344 rats into control and acute restraint (an animal model of psychosocial stress groups (n = 9-12/ group. We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the three hour restraint, as well as highly significant increases in blood glucocorticoid levels 21 hours after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  2. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging.

    Science.gov (United States)

    Buechel, Heather M; Popovic, Jelena; Staggs, Kendra; Anderson, Katie L; Thibault, Olivier; Blalock, Eric M

    2014-01-01

    Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  3. Repeated otilonium bromide administration prevents neurotransmitter changes in colon of rats underwent to wrap restraint stress.

    Science.gov (United States)

    Traini, Chiara; Evangelista, Stefano; Girod, Vincent; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana

    2017-04-01

    Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block of L- and T-type Ca(2+) channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress (WRS) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS. In particular, the drug prevents the decrease in SP-, NK1r-, nNOS-, VIP-, and S100β-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric ChAT-IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L-type Ca(2+) channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. Huntington CAG repeat size does not modify onset age in familial Parkinson’s disease: The GenePD Study

    Science.gov (United States)

    McNicoll, Christopher F.; Latourelle, Jeanne C.; MacDonald, Marcy E.; Lew, Mark F.; Suchowersky, Oksana; Klein, Christine; Golbe, Lawrence I.; Mark, Margery H.; Growdon, John H.; Wooten, G. Frederick; Watts, Ray L.; Guttman, Mark; Racette, Brad A.; Perlmutter, Joel S.; Ahmed, Anwar; Shill, Holly A.; Singer, Carlos; Saint-Hilaire, Marie H.; Massood, Tiffany; Huskey, Karen W.; DeStefano, Anita L.; Gillis, Tammy; Mysore, Jayalakshmi; Goldwurm, Stefano; Pezzoli, Gianni; Baker, Kenneth B.; Itin, Ilia; Litvan, Irene; Nicholson, Garth; Corbett, Alastair; Nance, Martha; Drasby, Edward; Isaacson, Stuart; Burn, David J.; Chinnery, Patrick F.; Pramstaller, Peter P.; Al-hinti, Jomana; Moller, Anette T.; Ostergaard, Karen; Sherman, Scott J.; Roxburgh, Richard; Snow, Barry; Slevin, John T.; Cambi, Franca; Gusella, James F.; Myers, Richard H.

    2009-01-01

    The ATP/ADP ratio reflects mitochondrial function and has been reported to be influenced by the size of the Huntington disease gene (HD) repeat. Impaired mitochondrial function has long been implicated in the pathogenesis of Parkinson’s disease (PD) and therefore, we evaluated the relationship of the HD CAG repeat size to PD onset age in a large sample of familial PD cases. PD affected siblings (n=495) with known onset ages from 248 families, were genotyped for the HD CAG repeat. Genotyping failed in 11 cases leaving 484 for analysis, including 35 LRRK2 carriers. All cases had HD CAG repeats (range 15 to 34) below the clinical range for HD, although 5.2 percent of the sample (n=25) had repeats in the intermediate range (the intermediate range lower limit=27; upper limit=35 repeats), suggesting that the prevalence of intermediate allele carriers in the general population is significant. No relation between the HD CAG repeat size and the age at onset for PD was found in this sample of familial PD. PMID:18649400

  5. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study

    Directory of Open Access Journals (Sweden)

    Quamruzzaman Quazi

    2007-12-01

    Full Text Available Abstract Background Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1, human 8-oxoguanine glycosylase (hOGG1 and apurinic/apyrimidinic endonuclease (APE1 genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07 compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase (95% CI 0.27, 1.42, a 0.98 increase (95% CI 033, 1.66 and a 0.85 increase (95% CI 0.27, 1.44 in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme.

  6. Psychological Growth and the Impact of Stress in Middle Age.

    Science.gov (United States)

    Medinger, Fred; Varghese, Raju

    1981-01-01

    Suggests that cycles of stress and anxiety in middle age may have a developmental etiology and may be a necessary part of the developmental process. Proposes reintegration of the cognitive structure to accommodate new elements reduces stress, leaving the adult changed with respect to certain beliefs. (Author/JAC)

  7. TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease

    Science.gov (United States)

    Lee, Ji-Hyun; Lee, Jong-Min; Ramos, Eliana Marisa; Gillis, Tammy; Mysore, Jayalakshmi S.; Kishikawa, Shotaro; Hadzi, Tiffany; Hendricks, Audrey E.; Hayden, Michael R.; Morrison, Patrick J.; Nance, Martha; Ross, Christopher A.; Margolis, Russell L.; Squitieri, Ferdinando; Gellera, Cinzia; Gomez-Tortosa, Estrella; Ayuso, Carmen; Suchowersky, Oksana; Trent, Ronald J.; McCusker, Elizabeth; Novelletto, Andrea; Frontali, Marina; Jones, Randi; Ashizawa, Tetsuo; Frank, Samuel; Saint-Hilaire, Marie-Helene; Hersch, Steven M.; Rosas, Herminia D.; Lucente, Diane; Harrison, Madaline B.; Zanko, Andrea; Abramson, Ruth K.; Marder, Karen; Sequeiros, Jorge; Landwehrmeyer, G. Bernhard; Network, Ira Shoulson; Myers, Richard H.; MacDonald, Marcy E.; Gusella, James F.

    2013-01-01

    Huntington's disease is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat whose length is the major determinant of age at onset but remaining variation appears to be due in part to the effect of genetic modifiers. GRIK2, which encodes GluR6, a mediator of excitatory neurotransmission in the brain, has been suggested in several studies to be a modifier gene based upon a 3′ untranslated region TAA trinucleotide repeat polymorphism. Prior to investing in detailed studies of the functional impact of this polymorphism, we sought to confirm its effect on age at onset in a much larger dataset than in previous investigations. We genotyped the HD CAG repeat and the GRIK2 TAA repeat in DNA samples from 2,911 Huntington's disease subjects with known age at onset, and tested for a potential modifier effect of GRIK2 using a variety of statistical approaches. Unlike previous reports, we detected no evidence of an influence of the GRIK2 TAA repeat polymorphism on age at motor onset. Similarly, the GRIK2 polymorphism did not show significant modifier effect on psychiatric and cognitive age at onset in HD. Comprehensive analytical methods applied to a much larger sample than in previous studies do not support a role for GRIK2 as a genetic modifier of age at onset of clinical symptoms in Huntington's disease. PMID:22771793

  8. Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Tadashi Nakamura

    2014-01-01

    Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

  9. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years, resul

  10. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years, resul

  11. Modelling Developmental Changes in Repeated-Sprint Ability by Chronological and Skeletal Ages in Young Soccer Players

    NARCIS (Netherlands)

    Valente-dos-Santos, J.; Coelho-e-Silva, M. J.; Martins, R. A.; Figueiredo, A. J.; Cyrino, E. S.; Sherar, L. B.; Vaeyens, R.; Huijgen, B. C. H.; Elferink-Gemser, M. T.; Malina, R. M.

    2012-01-01

    This study investigated the influence of chronological (CA) and skeletal ages (SA), anthropometry, aerobic endurance and lower limb explosive strength on developmental changes in repeated-sprint ability (RSA) in soccer players aged 11-17 years. Participants were annually followed over 5 years,

  12. Effect of Repeated Stress Treatments During the Follicular Phase and Early Pregnancy on Reproductive Performance of Gilts

    NARCIS (Netherlands)

    Soede, N.M.; Roelofs, J.B.; Verheijen, R.J.E.; Schouten, W.G.P.; Hazeleger, W.; Kemp, B.

    2007-01-01

    In pig husbandry, stress is being considered an important cause of impaired reproductive performance. Therefore, an experiment was performed to quantify effects of repeated stressors during the follicular phase and/or during early pregnancy on reproductive performance of gilts. Eighty-one cyclic

  13. Age, subjective stress, and depression after ischemic stroke.

    Science.gov (United States)

    McCarthy, Michael J; Sucharew, Heidi J; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Ferioli, Simona; Adeoye, Opeolu; Kleindorfer, Dawn O; Kissela, Brett M

    2016-02-01

    The incidence of stroke among younger adults in the United States is increasing. Few studies have investigated the prevalence of depressive symptoms after stroke among different age groups or the extent to which subjective stress at the time of stroke interacts with age to contribute to post-stroke depression. The present study examined whether there exists an age gradient in survivors' level of depressive symptoms and explored the extent to which financial, family, and health-related stress may also impact on depression. Bivariate analyses (N = 322) indicated significant differences in depression and stress by age group, as well as differences in age and stress by 3-month depression status. Linear regression analyses indicated that survivors between the ages of 25-54 and 55-64 years old had, on average, significantly higher depressive symptom scores. Those with financial, family, and health-related stress at the time of stroke, irrespective of age, also had significantly higher scores.

  14. Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset.

    Science.gov (United States)

    Swami, Meera; Hendricks, Audrey E; Gillis, Tammy; Massood, Tiffany; Mysore, Jayalakshmi; Myers, Richard H; Wheeler, Vanessa C

    2009-08-15

    The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets.

  15. Mild heat stress at a young age in Drosophila melanogaster leads to increased Hsp70 synthesis after stress exposure later in life

    Indian Academy of Sciences (India)

    Torsten Nygaard Kristensen; Jesper Givskov Sørensen; Volker Loeschcke

    2003-12-01

    In a number of animal species it has been shown that exposure to low levels of stress at a young age has a positive effect on stress resistance later in life, and on longevity. The positive effects have been attributed to the activation of defence/cleaning systems (heat shock proteins (Hsps), antioxidases, DNA repair) or to effects of a changed metabolic rate, or both. We investigated the effect of mild stress exposures early in life on Hsp70 synthesis after a harder stress exposure later in life in five isofemale lines of Drosophila melanogaster. Female flies were either exposed to repeated bouts of mild heat stress (3 h at 34°C) at a young age (days 2, 4 and 6 post-eclosion) or held under standard laboratory conditions. At 16 and 32 days of adult age, respectively, flies were exposed to a high temperature treatment known to induce Hsp70 in the investigated species (1 h at 37°ºC). Thereafter, the inducible Hsp70 levels were measured. Our data show a tendency towards increased Hsp70 synthesis with increased age for both ‘mild stress’ and ‘no stress’ flies. Moreover, the results show that flies exposed to mild stress at a young age synthesized more Hsp70 upon induction, compared to control flies, and that this difference was accentuated at 32 days compared to 16 days of age. Thus, bouts of mild heat stress at a young age impact on the physiological stress response system later in life. This may be caused by an increased ability to react to future stresses. Alternatively, the mild stress exposure at a young age may actually have caused cellular damages increasing the need for Hsp70 levels after stress exposure later in life. The importance of an Hsp70 upregulation (throughout life) in explaining the phenomenon of hormesis is discussed, together with alternative hypotheses, and suggestions for further studies.

  16. Markers of oxidant stress that are clinically relevant in aging and age-related disease.

    Science.gov (United States)

    Jacob, Kimberly D; Noren Hooten, Nicole; Trzeciak, Andrzej R; Evans, Michele K

    2013-03-01

    Despite the long held hypothesis that oxidant stress results in accumulated oxidative damage to cellular macromolecules and subsequently to aging and age-related chronic disease, it has been difficult to consistently define and specifically identify markers of oxidant stress that are consistently and directly linked to age and disease status. Inflammation because it is also linked to oxidant stress, aging, and chronic disease also plays an important role in understanding the clinical implications of oxidant stress and relevant markers. Much attention has focused on identifying specific markers of oxidative stress and inflammation that could be measured in easily accessible tissues and fluids (lymphocytes, plasma, serum). The purpose of this review is to discuss markers of oxidant stress used in the field as biomarkers of aging and age-related diseases, highlighting differences observed by race when data is available. We highlight DNA, RNA, protein, and lipid oxidation as measures of oxidative stress, as well as other well-characterized markers of oxidative damage and inflammation and discuss their strengths and limitations. We present the current state of the literature reporting use of these markers in studies of human cohorts in relation to age and age-related disease and also with a special emphasis on differences observed by race when relevant. Published by Elsevier Ireland Ltd.

  17. The Redox Stress Hypothesis of Aging

    OpenAIRE

    2011-01-01

    The main objective of this review is to examine the role of the endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the post-reproductive phase of life and eventually the death of the...

  18. The impact of repeated marathon running on cardiovascular function in the aging population

    Directory of Open Access Journals (Sweden)

    Karlstedt Erin

    2012-08-01

    Full Text Available Abstract Background Several studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV systolic dysfunction as assessed by both transthoracic echocardiography (TTE and cardiovascular magnetic resonance (CMR. Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial. Objectives To assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT, and CMR. Methods A total of 25 healthy volunteers (21 males, 55 ± 4 years old from the 2010 and 2011 Manitoba Full Marathons (26.2 miles were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon. Results All participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT. Conclusions Marathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

  19. Ageing under Shear: Effect of Stress and Temperature Field

    Science.gov (United States)

    Shukla, Asheesh; Joshi, Yogesh M.

    2008-07-01

    In this work we studied the effect of oscillatory stress and temperature on the ageing dynamics of aqueous suspension of laponite. At the higher magnitude of stress, elastic and viscous moduli of the system underwent a sharp rise with the ageing time. The age at the onset of rise and the sharpness of the same increased with the magnitude of stress. We propose that at the beginning of ageing, the strain associated with the oscillatory stress field affects the lower modes in the relaxation time distribution. The higher modes, which are not significantly affected by the deformation field, continue to grow increasing the viscosity of the system thereby lowering the magnitude of the deformation field. Progressive decrease in the later reduces the range of relaxation modes affected by it. This dynamics eventually leads to an auto-catalytic increase in the elastic and viscous moduli. An increase in temperature accelerates the ageing process by shifting the ageing dynamics to a lower ageing time. This is due the microscopic relaxation dynamics, which causes ageing, becomes faster with increase in the temperature.

  20. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

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    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  1. Revisiting an age-old question regarding oxidative stress

    Science.gov (United States)

    Edrey, Yael H.; Salmon, Adam B.

    2014-01-01

    Significant advances in maintaining health throughout life can be made through a clear understanding of the fundamental mechanisms that regulate aging. The Oxidative Stress Theory of Aging (OSTA) is likely the most well-studied mechanistic theory of aging and suggests that the rate of aging is controlled by accumulation of oxidative damage. To directly test the OSTA, aging has been measured in several lines of mice with genetic alteration of the expression of enzymatic antioxidants. Under its strictest interpretation, these studies do not support the OSTA, as modulation of antioxidant expression does not generally affect mouse lifespan. However, the incidence of many age-related diseases and pathologies is altered in these models suggesting that oxidative stress does significantly impact some aspects of the aging process. Further, oxidative stress may affect aging in disparate patterns among tissues or under different environmental conditions. In this review, we summarize the current literature regarding aging in antioxidant mutant mice and offer several interpretations on their support of the OSTA. PMID:24704971

  2. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study

    National Research Council Canada - National Science Library

    Breton, Carrie V; Kile, Molly L; Catalano, Paul J; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Christiani, David C

    2007-01-01

    .... Generation of oxidative stress may contribute to arsenic carcinogenesis. To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG...

  3. Survival and longevity improvements at extreme ages: an interpretation assuming an ecological stress theory of aging.

    Science.gov (United States)

    Parsons, Peter A

    2007-04-01

    The primary determinant of survival during aging is the energetic efficiency and metabolic stability required to counter the accumulated internal and external stresses of a lifetime. Hence, genetically stress-resistant individuals should accumulate with age; frailer, less robust, less energetically efficient and less metabolically stable individuals should succumb in parallel. This selection process implies the accumulation of energetically efficient stress-resistant individuals with age to the exclusion of all others. High additive genetic variability for survival is expected under extreme circumstances, however there is limited evidence close to the absolute extremes of life that diversity may fall. At this stage, only a few highly adaptive, oxidative-stress-resistant and presumably somewhat homozygous genotypes should remain. Therefore a fall in variability may occur in these outliers, when frailer individuals are unable to cope and are eliminated at extreme ages. This process could provide an explanation of mortality-rate declines in domesticated (laboratory) and free-living populations of the extremely old. That is, mortality-rate declines may be an expectation from a process of genetic sorting resulting from the accumulated responses to environmental stress over time. Application of an ecological stress theory of aging, which combines the external stresses to which organisms are exposed with internal stresses, appears to be the prerequisite for this conclusion.

  4. The development of behavioral and endocrine abnormalities in rats after repeated exposure to direct and indirect stress.

    Science.gov (United States)

    Daniels, Willie Mark Uren; de Klerk Uys, Joachim; van Vuuren, Petra; Stein, Daniel Joseph

    2008-04-01

    The present study compared the effects of direct and indirect stress on the behavior and hypothalamic-pituitary-adrenal axis of rats. Animals were placed in a two compartment box. In one compartment the direct stressed rat was subjected to electric foot shocks randomly applied for 10 minutes (0.5 mA of 1 s duration). In the adjacent compartment, the indirect stressed rats witnessed the application of these electric foot shocks. Our data showed substantial behavioral changes in the open field test, but limited effects in the elevated plus maze. The findings suggested that single and repeated stress exposure may have different consequences, that the effects of stress exposure may develop over time and persist for an extended period, and that both direct and indirect stressed rats displayed a hyposensitive HPA axis following acute restraint stress. Overall our observations moderately indicate direct exposure to elicit behavioral changes, and both direct and indirect exposure to stress to result in aberrations within the neuroendocrine system. With additional development our stress models may be considered for studying the complex interrelationship between an external stressor, and the experience of the organism.

  5. Job stress and mortality in older age

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    Beata Tobiasz-Adamczyk

    2013-06-01

    Full Text Available Objectives: This paper aims to assess the relationship between the determinants of the psychosocial work environment, as expressed in terms of JDC or ERI models, and all-cause mortality in older individuals. Materials and Methods: The baseline study was conducted on a cohort comprising a random sample of 65-year-old community-dwelling citizens of Kraków, Poland. All of the 727 participants (410 women, 317 men were interviewed in their households in the period between 2001 and 2003; a structured questionnaire was used regarding their occupational activity history, which included indexes measuring particular dimensions of their psychosocial work environment based on Karasek's Job Demand-Control model and Siegrist's Effort-Reward Imbalance model, as well as health-related quality of life and demographic data. Mortality was ascertained by monitoring City Vital Records for 7 years. Analyses were conducted separately for men and women, with the multivariate Cox proportional hazard model. Results: During a 7-year follow-up period, 59 participants (8.1% died, including 21 women (5.1% of total women and 38 men (12% (p < 0.05. Significant differences in the number of deaths occurred regarding disproportion between physical demands and control in men: those with low physical demands and low control died three times more often than those with high control, regardless of the level of demands. The multivariate Cox proportional hazard model showed that significantly higher risk of death was observed only in men with low physical demands and low control, compared to those with low physical demands and high control (Exp(B = 4.65, 95% CI: 1.64-13.2. Conclusions: Observed differences in mortality patterns are similar to the patterns of relationships observed in health-related quality of life (HRQoL level at the beginning of old age; however, the relationship between efforts and rewards or demands and control and mortality was not fully confirmed.

  6. The role of oxidative stress and inflammation in cardiovascular aging.

    Science.gov (United States)

    Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Wan, Wenbin; Sun, Tao

    2014-01-01

    Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66(Shc), and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

  7. Oxidation stress role in age-related cataractogenesis

    Directory of Open Access Journals (Sweden)

    Žorić Lepša

    2010-01-01

    Full Text Available Introduction. Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress. Oxidation stress and its form caused by ultraviolet light-photo-oxidative stress - are considered to be crucial in the etiopatho­genesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens posses a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  8. Oxidative stress and ageing of the post-ovulatory oocyte.

    Science.gov (United States)

    Lord, Tessa; Aitken, R John

    2013-12-01

    With extended periods of time following ovulation, the metaphase II stage oocyte experiences deterioration in quality referred to as post-ovulatory oocyte ageing. Post-ovulatory ageing occurs both in vivo and in vitro and has been associated with reduced fertilization rates, poor embryo quality, post-implantation errors and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been established, the molecular mechanisms controlling this process are not well defined. This review analyses the relationships between biochemical changes exhibited by the ageing oocyte and the symptoms associated with the ageing phenotype. We also discuss molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We propose that oxidative stress may act as the initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to cause a decline in levels of critical cell cycle factors such as maturation-promoting factor, impair calcium homoeostasis, induce mitochondrial dysfunction and directly damage multiple intracellular components of the oocyte such as lipids, proteins and DNA. Finally, this review addresses current strategies for delaying post-ovulatory oocyte ageing with a particular focus on the potential use of compounds such as caffeine or selected antioxidants in the development of more refined media for the preservation of oocyte integrity during IVF procedures.

  9. Early Age Thermal Conditioning Improves Broiler Chick's Response to Acute Heat Stress at Marketing Age

    Directory of Open Access Journals (Sweden)

    Ahmed M. Hassan

    2012-01-01

    Full Text Available Problem statement: Acute heat stress at marketing age especially in broiler chickens raised in open houses with reduced means of heat exchange leads to economic losses. The objective of this study was to determine beneficial effects of early age thermal conditioning in reducing adverse effects of acute heat stress and decrease losses. Approach: Ninety one day-old broiler chicks were randomly assigned to one of three treatments (n = 30: (1 control (normally raised, (2 early age thermal conditioning (exposed to temperature of 40±1°C for 24 h at 5th day of age, then raised as control chicks and (3 chronic stress (exposed to 33±2°C from day one till 6 weeks of age. At 42nd day of age, all chicks were subjected to acute heat stress of 39±2°C for 2 h. Blood samples were collected from all groups before and after exposure to acute heat stress. Results: Blood pH increased in both controls and thermally-conditioned chicks after exposure to acute heat stress coinciding with significant decrease in blood carbon dioxide pressure (pCo2 in controls only. Blood potassium level decreased in controls, while in thermally-conditioned or chronically-stressed no significant changes were observed. Blood sodium level showed a trend toward decreased levels in controls while a trend toward increased levels was observed in both thermally-conditioned and chronically-stressed birds. Importantly, significant reductions were observed in total erythrocyte count and hemoglobin level in chronically-stressed birds as compared to other groups before and after acute stress exposure. Hetrophil/lymphocyte ratio increased in both controls and thermally-conditioned chicks after acute heat exposure, but not in chronically-stressed birds. Conclusion: When exposed to acute heat stress at marketing age, chicks subjected to early age thermal conditioning responded very similar to birds adapted to chronic heat stress indicating a protective role of early age thermal conditioning.

  10. Peripheral biomarkers of oxidative stress in aging and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Tania Marcourakis

    Full Text Available Abstract Aging is associated with a greatly increased incidence of a number of neurodegenerative disorders, including Alzheimer's disease (AD, Parkinson's disease (PD and amyotrophic lateral sclerosis (ALS. These conditions are associated with chronic inflammation, which generates oxygen reactive species, ultimately responsible for a process known as oxidative stress. It is well established that this process is the culprit of neurodegeneration, and there are also mounting evidences that it is not restricted to the central nervous system. Indeed, several studies, including some by our group, have demonstrated that increased peripheral oxidative stress markers are associated to aging and, more specifically, to AD. Therefore, it is very instigating to regard aging and AD as systemic conditions that might be determined by studying peripheral markers of oxidative stress.

  11. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress

    Directory of Open Access Journals (Sweden)

    Muhammad Farhan

    2016-09-01

    Full Text Available Background: Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI, has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Methods: Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits. Results: Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg. Conclusion: The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.

  12. Over-representation of repeats in stress response genes: a strategy to increase versatility under stressful conditions?

    OpenAIRE

    Rocha, Eduardo P. C.; Matic, Ivan; Taddei, François

    2002-01-01

    The survival of individual organisms facing stress is enhanced by the induction of a set of changes. As the intensity, duration and nature of stress is highly variable, the optimal response to stress may be unpredictable. To face such an uncertain future, it may be advantageous for a clonal population to increase its phenotypic heterogeneity (bet-hedging), ensuring that at least a subset of cells would survive the current stress. With current techniques, assessing the extent of this variabili...

  13. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2017-01-01

    BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients with...

  14. The role of oxidative stress in nervous system aging.

    Science.gov (United States)

    Sims-Robinson, Catrina; Hur, Junguk; Hayes, John M; Dauch, Jacqueline R; Keller, Peter J; Brooks, Susan V; Feldman, Eva L

    2013-01-01

    While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/-)) mice, a mouse model of increased oxidative stress. Sod1(-/-) mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+) mice at 30 months and the Sod1(-/-) mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.

  15. Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver.

    Directory of Open Access Journals (Sweden)

    Jong-Min Lee

    Full Text Available BACKGROUND: Age at onset of Huntington's disease (HD is largely determined by the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat undergoes tissue-specific somatic instability, prevalent in brain regions that are disease targets, suggesting a potential role for somatic CAG repeat instability in modifying HD pathogenesis. Thus, understanding underlying mechanisms of somatic CAG repeat instability may lead to discoveries of novel therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes over time may provide insights into the mechanisms underlying CAG repeat instability. METHODOLOGY/PRINCIPAL FINDINGS: To understand how the HTT CAG repeat length changes over time, we quantified somatic instability of the CAG repeat in Huntington's disease CAG knock-in mice from 2-16 months of age in liver, striatum, spleen and tail. The HTT CAG repeat in spleen and tail was very stable, but that in liver and striatum expanded over time at an average rate of one CAG per month. Interestingly, the patterns of repeat instability were different between liver and striatum. Unstable CAG repeats in liver repeatedly gained similar sizes of additional CAG repeats (approximately two CAGs per month, maintaining a distinct population of unstable repeats. In contrast, unstable CAG repeats in striatum gained additional repeats with different sizes resulting in broadly distributed unstable CAG repeats. Expanded CAG repeats in the liver were highly enriched in polyploid hepatocytes, suggesting that the pattern of liver instability may reflect the restriction of the unstable repeats to a unique cell type. CONCLUSIONS/SIGNIFICANCE: Our results are consistent with repeat expansion occurring as a consequence of recurrent small repeat insertions that differ in different tissues. Investigation of the specific mechanisms that underlie liver and striatal instability will contribute to our understanding of the relationship between

  16. Cellular stress responses for monitoring and modulating ageing

    DEFF Research Database (Denmark)

    Demirovic, Dino; Schnebert, Sylvianne; Nizard, Carine

    2013-01-01

    Cellular stress response is a crucial factor in maintaining efficient homeodynamics for survival, health and longevity. Both the immediate and delayed responses to external and internal stressors effectively determine the molecular biochemical and physiological stability in a dynamic and interact......Cellular stress response is a crucial factor in maintaining efficient homeodynamics for survival, health and longevity. Both the immediate and delayed responses to external and internal stressors effectively determine the molecular biochemical and physiological stability in a dynamic...... and interactive manner. There are three main aspects of stress responses: (i) immediate stress response involving extra- and intra-cellular signaling during the period of disturbance and exposure to the stressors; (ii) delayed stress response involving sensors and modulators in the presence of stressors or after......, development and ageing. Our aim is to define and establish the immediate and delayed stress profiles of normal human skin fibroblasts undergoing ageing in vitro. This is done efficiently by using various cellular, molecular and antibody-based detection methods, combined with functional assays, such as wound...

  17. REST and stress resistance in ageing and Alzheimer's disease

    Science.gov (United States)

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.

    2014-03-01

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

  18. [Oxidation stress role in age-related cataractogenesis].

    Science.gov (United States)

    Zorić, Lepsa; Colak, Emina; Canadanović, Vladimir; Kosanović-Jaković, Natalija; Kisić, Bojana

    2010-01-01

    Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress and its form caused by ultraviolet light- photo-oxidative stress--are considered to be crucial in the etiopathogenesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens possess a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  19. Repeated stressors do not provoke habituation or accumulation of the stress response in the catfish Rhamdia quelen

    Directory of Open Access Journals (Sweden)

    Gessi Koakoski

    2013-06-01

    Full Text Available Fish repeatedly experience stressful situations under experimental and aquaculture conditions, even in their natural habitat. Fish submitted to sequential stressors can exhibit accumulation or habituation on its cortisol response. We posed a central question about the cortisol response profiles after exposure to successive acute stressors of a similar and different nature in Rhamdia quelen. We have shown that successive acute stressors delivered with 12-h, 48-h, and 1-week intervals provoked similar cortisol responses in juvenile R. quelen, without any habituation or accumulation. The cumulative stress response is more associated to short acute stressors with very short intervals of minutes to hours. In our work, we used an interval as short as 12h, and no cumulative response was found. However, if the length of time between stressors is of a day or week as used in our work the most common and an expected phenomenon is the attenuation of the response. Thus, also, the absence of both accumulation of the stress response and the expected habituation is an intriguing result. Our results show that R. quelen does not show habituation or accumulation in its stress responses to repeated stressors, as reported for other fish species

  20. Is the oxidative stress theory of aging dead?

    Science.gov (United States)

    Pérez, Viviana I; Bokov, Alex; Van Remmen, Holly; Mele, James; Ran, Qitao; Ikeno, Yuji; Richardson, Arlan

    2009-10-01

    Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.

  1. Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

    Science.gov (United States)

    Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

    2015-06-01

    We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

  2. Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro.

    Science.gov (United States)

    Demirovic, Dino; de Toda, Irene Martinez; Nizard, Carine; Rattan, Suresh I S

    2014-12-01

    Repeated exposure to mild heat shock (HS) has been shown to induce a wide range of health promoting hormetic effects in various biological systems, including human cells undergoing aging in vitro. In order to understand how cells distinguish between mild and severe stress, we have investigated the extent of early and immediate HS response by analyzing the nuclear translocation of the transcription factor heat shock factor-1 (HSF1), in serially passaged normal adult human facial skin fibroblasts exposed to mild (41 °C) or severe (43 °C) HS. Cells respond differently when exposed to mild and severe HS at different passage levels in terms of the extent of HSF1 translocation. In early passage young cells there was a 5-fold difference between mild and severe HS in the extent of HSF1 translocation. However, in near senescent late passage cells, the difference between mild and severe stress in terms of the extent of HSF1 translocation was reduced to less than 2-fold. One of the reasons for this age-related attenuation of heat shock response is due to the fact there was a higher basal level of HSF1 in the nuclei of late passage cells, which is indicative of increased intrinsic stress during cellular aging. These observations are consistent with previously reported data that whereas repeated mild stress given at younger ages can slow down aging and increase the lifespan, the same level of stress given at older ages may not provide the same benefits. Therefore, elucidating the early and immediate steps in the induction of stress response can be useful in deciding whether a particular level of stress is potentially hormetically beneficial or not.

  3. Baseline and stress-induced glucocorticoid concentrations are not repeatable but covary within individual great tits (Parus major).

    Science.gov (United States)

    Baugh, Alexander T; van Oers, Kees; Dingemanse, Niels J; Hau, Michaela

    2014-11-01

    In evolutionary endocrinology, there is a growing interest in the extent and basis of individual variation in endocrine traits, especially circulating concentrations of hormones. This is important because if targeted by selection, such individual differences present the opportunity for an evolutionary response to selection. It is therefore necessary to examine whether hormone traits are repeatable in natural populations. However, research in this area is complicated by the fact that different hormone traits can be correlated. The nature of these trait correlations (i.e., phenotypic, within-, or among-individual) is critically relevant in terms of the evolutionary implications, and these in turn, depend on the repeatability of each hormone trait. By decomposing phenotypic correlations between hormone traits into their within- and among-individual components it is possible to describe the multivariate nature of endocrine traits and generate inferences about their evolution. In the present study, we repeatedly captured individual great tits (Parus major) from a wild population and measured plasma concentrations of corticosterone. Using a mixed-modeling approach, we estimated repeatabilities in both initial (cf. baseline; CORT0) and stress-induced concentrations (CORT30) and the correlations between those traits among- and within-individuals. We found a lack of repeatability in both CORT0 and CORT30. Moreover, we found a strong phenotypic correlation between CORT0 and CORT30, and due to the lack of repeatability for both traits, there was no among-individual correlation between these two traits-i.e., an individual's average concentration of CORT0 was not correlated with its average concentration of CORT30. Instead, the phenotypic correlation was the result of a strong within-individual correlation, which implies that an underlying environmental factor co-modulates changes in initial and stress-induced concentrations within the same individual over time. These results

  4. Calcium signaling alterations, oxidative stress, and autophagy in aging.

    Science.gov (United States)

    Ureshino, Rodrigo Portes; Rocha, Katiucha Karolina; Lopes, Guiomar Silva; Bincoletto, Cláudia; Smaili, Soraya Soubhi

    2014-07-01

    Aging is a multi-factorial process that may be associated with several functional and structural deficits which can evolve into degenerative diseases. In this review, we present data that may depict an expanded view of molecular aging theories, beginning with the idea that reactive oxygen species (ROS) are the major effectors in this process. In addition, we have correlated the importance of autophagy as a neuroprotective mechanism and discussed a link between age-related molecules, Ca(2+) signaling, and oxidative stress. There is evidence suggesting that alterations in Ca(2+) homeostasis, including mitochondrial Ca(2+) overload and alterations in electron transport chain (ETC) complexes, which increase cell vulnerability, are linked to oxidative stress in aging. As much as Ca(2+) signaling is altered in aged cells, excess ROS can be produced due to an ineffective coupling of mitochondrial respiration. Damaged mitochondria might not be removed by the macroautophagic system, which is hampered in aging by lipofuscin accumulation, boosting ROS generation, damaging DNA, and, ultimately, leading to apoptosis. This process can lead to altered protein expression (such as p53, Sirt1, and IGF-1) and progress to cell death. This cycle can lead to increased cell vulnerability in aging and contribute to an increased susceptibility to degenerative processes. A better understanding of Ca(2+) signaling and molecular aging alterations is important for preventing apoptosis in age-related diseases. In addition, caloric restriction, resveratrol and autophagy modulation appear to be predominantly cytoprotective, and further studies of this process are promising in age-related disease therapeutics.

  5. The Role of Oxidative Stress in Aging and Dementia

    Directory of Open Access Journals (Sweden)

    Joana Teixeira

    2014-12-01

    Full Text Available Introduction: Biologic aging is a process, and oxidative stress theory, which is one of the most accepted biological theories for aging, states that oxidative stress causes cumulative damage to mitochondrial DNA resulting in cellular senescence. Dementia is a neurodegenerative disorder whose major risk factor is aging. Although the exact neuronal lesion mechanisms underlying neurodegenerative disorders, including dementia, are not yet known, most recent studies suggest oxidative stress and mitochondrial dynamics’ role in the process.Objective: Literature review on the role of oxidative stress’ role in aging and dementia.Methods: Literature review of selected arti-cles and books deemed relevant by the authors, supplemented by Medline/Pubmed database search using combinations of the following key-words: “oxidative stress”, “de-mentia”, “aging” and “pathogenesis”, published between 1950 and 2013. References of the selected articles and books were also considered.Results: In the last five years new research has been undertaken that enlightens the relation between oxidative stress and aging. One of the considered hypotheses states that during aging, the homeostatic regulation of biogenesis, dynamics and autophagic turnover of mitochondria disturbs their functioning, resulting in cellular senescence. Consequently, the oxidative burden may reach a critical threshold above which apoptosis is triggered, leading to irreversible mitochondrial derangement and cellular death. Although the exact neuronal lesion mechanisms underlying dementias are not known, multiple studies have consistently found increased oxidative damage in brain of patients with Alzheimer disease and recent data suggests involvement of mitochondrial dynamics in dementia processes, such as in aging.Conclusions: Most recent studies suggest the role of oxidative stress and mitochondrial dynamics’ in aging and dementia, either directly or

  6. Do Stress Trajectories Predict Mortality in Older Men? Longitudinal Findings from the VA Normative Aging Study

    Directory of Open Access Journals (Sweden)

    Carolyn M. Aldwin

    2011-01-01

    Full Text Available We examined long-term patterns of stressful life events (SLE and their impact on mortality contrasting two theoretical models: allostatic load (linear relationship and hormesis (inverted U relationship in 1443 NAS men (aged 41–87 in 1985; M = 60.30, SD = 7.3 with at least two reports of SLEs over 18 years (total observations = 7,634. Using a zero-inflated Poisson growth mixture model, we identified four patterns of SLE trajectories, three showing linear decreases over time with low, medium, and high intercepts, respectively, and one an inverted U, peaking at age 70. Repeating the analysis omitting two health-related SLEs yielded only the first three linear patterns. Compared to the low-stress group, both the moderate and the high-stress groups showed excess mortality, controlling for demographics and health behavior habits, HRs = 1.42 and 1.37, ps <.01 and <.05. The relationship between stress trajectories and mortality was complex and not easily explained by either theoretical model.

  7. Skin aging and oxidative stress: Equol's anti-aging effects via biochemical and molecular mechanisms.

    Science.gov (United States)

    Lephart, Edwin D

    2016-11-01

    Oxygen in biology is essential for life. It comes at a cost during normal cellular function, where reactive oxygen species (ROS) are generated by oxidative metabolism. Human skin exposed to solar ultra-violet radiation (UVR) dramatically increases ROS production/oxidative stress. It is important to understand the characteristics of human skin and how chronological (intrinsic) aging and photo-aging (extrinsic aging) occur via the impact of ROS production by cascade signaling pathways. The goal is to oppose or neutralize ROS insults to maintain good dermal health. Botanicals, as active ingredients, represent one of the largest categories used in dermatology and cosmeceuticals to combat skin aging. An emerging botanical is equol, a polyphenolic/isoflavonoid molecule found in plants and food products and via gastrointestinal metabolism from precursor compounds. Introductory sections cover oxygen, free radicals (ROS), oxidative stress, antioxidants, human skin aging, cellular/molecular ROS events in skin, steroid enzymes/receptors/hormonal actions and genetic factors in aging skin. The main focus of this review covers the characteristics of equol (phytoestrogenic, antioxidant and enhancement of extracellular matrix properties) to reduce skin aging along with its anti-aging skin influences via reducing oxidative stress cascade events by a variety of biochemical/molecular actions and mechanisms to enhance human dermal health. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Oxidative Stress in Aging: Advances in Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Daniel Ortuño-Sahagún

    2014-01-01

    Full Text Available Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL. Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS], which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8, naked mole-rat (Heterocephalus glaber, and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS and oxidative stress in aging.

  9. Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle

    DEFF Research Database (Denmark)

    Sahlin, Kent; Nielsen, Jens Steen; Mogensen, Martin

    2006-01-01

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca(2+...

  10. Recovery from hybrid breakdown in a marine invertebrate is faster, stronger and more repeatable under environmental stress.

    Science.gov (United States)

    Hwang, A S; Pritchard, V L; Edmands, S

    2016-09-01

    Understanding how environmental stress alters the consequences of hybridization is important, because the rate of hybridization and the likelihood of hybrid speciation both appear elevated in harsh, disturbed or marginal habitats. We assessed fitness, morphometrics and molecular genetic composition over 14 generations of hybridization between two highly divergent populations of the marine copepod Tigriopus californicus. Replicated, experimental hybrid populations in both control and high-salinity conditions showed a decline in fitness, followed by a recovery. Recovery was faster in the salinity stress treatment, returning to parental levels up to two generations earlier than in the control. This recovery was stable in the high-salinity treatment, whereas in the control treatment, fitness dropped back below parental levels at the final time point. Recovery in the high-salinity treatment was also stronger in terms of competitive fitness and heat-shock tolerance. Finally, consequences of hybridization were more repeatable under salinity stress, where among-replicate variance for survivorship and molecular genetic composition was lower than in the control treatment. In a system with low effective population sizes (estimates ranged from 17 to 63), where genetic drift might be expected to be the predominate force, strong selection under harsh environmental conditions apparently promoted faster, stronger and more repeatable recovery from depressed hybrid fitness.

  11. Repeatability of frequency of corrective foot pressure during balance control in children aged between 2 and 7.

    Science.gov (United States)

    Sobera, Małgorzata; Siedlecka, Bożena

    2010-01-01

    The frequency of corrective signal (the centre of corrective (COC) signal), which is the decomposition of COP (centre of pressure) and estimated COM (centre of mass) time series, is one of the indicators reflecting the quality of postural control during stance. Young children, in the period of intensive development, gradually improve the quality of postural control in a daily life. The purpose of this paper was to describe the time series of corrective centre of foot pressure repeatability in young children aged between 2 and 7 during body stability in natural stance position. 272 healthy children aged between 2 and 7 were divided into 6 age groups. Two AccuSway force platforms were used (one foot of the subject was on one platform, the second foot, on the other). The COP trajectories were the basis for the calculation of the frequency stability indices in frontal and sagittal planes for the left leg and right leg separately. The COC signals were collected by the method based on the Kuczyński viscoelastic model. In order to assess the repeatability, the concordance correlation coefficient (CCC) was used between the 1st and the 2nd trials, the 2nd and the 3rd trials, and the 1st and the 3rd trials. The maturation of postural control system goes rather slowly in two youngest groups which showed the poor repeatability in COC frequency between the 2nd and the 3rd years of life. From the 4th to the 7th year of life the inter-session repeatability rapidly increases in three consecutive trials. Poor difference of frequency concordance was found between the left and right lower limbs. It is concluded that the frequency of corrective foot pressure is the reliable indicator of postural control for children aged between 4 and 7, but not for younger ones.

  12. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    Science.gov (United States)

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research.

  13. [Glycation of mitochondrial proteins, oxidative stress and aging].

    Science.gov (United States)

    Naudí, Alba; Jové, Mariona; Ayala, Victoria; Portero-Otín, Manuel; Pamplona, Reinald

    2010-01-01

    Mitochondrial proteins can be modified by glycation reactions from endogenous dicarbonyl compounds such as physiologically generated methylglyoxal and glyoxal. This modification could cause structural and functional changes in the proteins Consequently, dicarbonyl attack of the mitochondrial proteome may be an event leading to mitochondrial dysfunction and thus, to oxidative stress. These protein chemical modifications can play an important role in the physiological aging process and age-associated diseases, where both mitochondrial defects and increased dicarbonyl concentrations have been found. Future research should address the functional changes in mitochondrial proteins that are the targets for dicarbonyl glycation.

  14. Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration.

    Science.gov (United States)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie; Sagoo, Mandeep S; Tufail, Adnan; Balaggan, Kamaljit S; Patel, Praveen J

    2017-05-01

    The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Stressful situations and coping strategies in relation to age.

    Science.gov (United States)

    Richaud de Minzi, María Cristina; Sacchi, Carla

    2005-10-01

    Whether people cope differently with negative events at different ages was assessed by relation to age by type of situation perceived as potentially stressful and by type of coping strategy used, and also whether the kind of coping strategy used to reduce the potential stressor was related to type of stressor. To do this the factor structure of the Spanish version of the Ways of Coping Checklist of Lazarus and Folkman was examined in an Argentine sample of 153. The factor analysis of checklist scores identified five factors: Cognitive redefinition, Problem focus, Seeking social support, Wishful thinking, and Avoidance. For two groups, ages 20 to 24 and 40 to 45 years, analysis indicated a significant association of type of situation perceived as potentially stressful with age. The middle-age group (40-45 yr.) chose a way of coping in problem solution but the young adult group (20-24 yr.) seemed more often to elude problems. It appears that the type of stressor influences type of coping.

  16. A maximal cycle test with good validity and high repeatability in adults of all ages

    DEFF Research Database (Denmark)

    Eriksen, L; Tolstrup, J S; Larsen, Steen

    2014-01-01

    In 11 680 individuals (18-85 years) maximal oxygen consumption (VO2max) was estimated indirectly in a maximal cycle test using a prediction model developed in a young population (15-28 years). A subsample of 182 individuals (23-77 years) underwent 2 maximal cycle tests with VO2max estimated...... we suggest a new prediction model of VO2max. The maximal cycle test was highly repeatable....

  17. Physiological responding to stress in middle-aged males enriched for longevity: a social stress study.

    Science.gov (United States)

    Jansen, Steffy W M; van Heemst, Diana; van der Grond, Jeroen; Westendorp, Rudi; Oei, Nicole Y L

    2016-01-01

    Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity might be a more adaptive response to stress. To investigate this, male middle-aged offspring from long-lived families (n = 31) and male non-offspring (with no familial history of longevity) (n = 26) were randomly allocated to the Trier Social Stress Test or a control condition in an experimental design. Physiological (cortisol, blood pressure, heart rate) and subjective responses were measured during the entire procedure. The results showed that Offspring had lower overall cortisol levels compared to Non-offspring regardless of condition, and lower absolute cortisol output (AUCg) during stress compared to Non-Offspring, while the increase (AUCi) did not differ between groups. In addition, systolic blood pressure in Offspring was lower compared to Non-offspring during the entire procedure. At baseline, Offspring had significantly lower systolic blood pressure and reported less subjective stress than Non-offspring and showed a trend towards lower heart rate. Offspring from long-lived families might thus be less stressed prior to potentially stressful events and consequently show overall lower levels in physiological responses. Although attenuated physiological responding cannot be ruled out, lower starting points and a lower peak level in physiological responding when confronted with an actual stressor, might already limit damage due to stress over a lifetime. Lower physiological responding may also contribute to the lower prevalence of cardiovascular diseases and other stress-related diseases in healthy longevity.

  18. Modification of hippocampal markers of synaptic plasticity by memantine in animal models of acute and repeated restraint stress: implications for memory and behavior.

    Science.gov (United States)

    Amin, Shaimaa Nasr; El-Aidi, Ahmed Amro; Ali, Mohamed Mostafa; Attia, Yasser Mahmoud; Rashed, Laila Ahmed

    2015-06-01

    Stress is any condition that impairs the balance of the organism physiologically or psychologically. The response to stress involves several neurohormonal consequences. Glutamate is the primary excitatory neurotransmitter in the central nervous system, and its release is increased by stress that predisposes to excitotoxicity in the brain. Memantine is an uncompetitive N-methyl D-aspartate glutamatergic receptors antagonist and has shown beneficial effect on cognitive function especially in Alzheimer's disease. The aim of the work was to investigate memantine effect on memory and behavior in animal models of acute and repeated restraint stress with the evaluation of serum markers of stress and the expression of hippocampal markers of synaptic plasticity. Forty-two male rats were divided into seven groups (six rats/group): control, acute restraint stress, acute restraint stress with Memantine, repeated restraint stress, repeated restraint stress with Memantine and Memantine groups (two subgroups as positive control). Spatial working memory and behavior were assessed by performance in Y-maze. We evaluated serum cortisol, tumor necrotic factor, interleukin-6 and hippocampal expression of brain-derived neurotrophic factor, synaptophysin and calcium-/calmodulin-dependent protein kinase II. Our results revealed that Memantine improved spatial working memory in repeated stress, decreased serum level of stress markers and modified the hippocampal synaptic plasticity markers in both patterns of stress exposure; in ARS, Memantine upregulated the expression of synaptophysin and brain-derived neurotrophic factor and downregulated the expression of calcium-/calmodulin-dependent protein kinase II, and in repeated restraint stress, it upregulated the expression of synaptophysin and downregulated calcium-/calmodulin-dependent protein kinase II expression.

  19. Physiological responding to stress in middle-aged males enriched for longevity: a social stress study

    NARCIS (Netherlands)

    Jansen, S.W.M.; van Heemst, D.; van der Grond, J.; Westendorp, R.; Oei, N.Y.L.

    2016-01-01

    Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity mig

  20. Physiological responding to stress in middle-aged males enriched for longevity: a social stress study

    NARCIS (Netherlands)

    Jansen, S.W.M.; van Heemst, D.; van der Grond, J.; Westendorp, R.; Oei, N.Y.L.

    2016-01-01

    Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity mig

  1. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

    Indian Academy of Sciences (India)

    Y-J Choi; J Y Kim; S B Yoo; J-H Lee; J W Jahng

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

  2. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture

    Directory of Open Access Journals (Sweden)

    Oluyomi Stephen Adeyemi

    2014-01-01

    Full Text Available This study determined the effect of the oral and repeated administration of Fijk herbal mixture on rat biochemical and morphological parameters. Twenty-four Wistar rats were distributed into four groups of 6. Group A served as control and received oral administration of distilled water daily. The experimental groups B, C, and D were daily and orally exposed to Fijk herbal mixture at 15, 30, and 45 mg/kg, respectively. Treatments lasted for 21 days. The rats were sacrificed under mild diethyl ether anesthesia 24 hr after cessation of treatment. The blood and liver samples were collected and used for the biochemical and morphological analyses. Oral exposure to Fijk caused elevated levels of rat plasma ALT, AST, triglycerides, LDL, and MDA. In contrast, rat plasma HDL, GSH, and ALP levels were lowered by Fijk oral exposure. Also, the herbal remedy caused a dose-dependent elevation in the plasma atherogenic index. The histopathology examinations of rat liver sections revealed inimical cellular alterations caused by repeated exposure to Fijk. Study provides evidence that oral and repeated exposure to Fijk in rats raised the atherogenic index and potentiated oxidative stress as well as hepatic injury.

  3. Insomnia management for ageing employees with job stress

    Directory of Open Access Journals (Sweden)

    Roja I.

    2014-01-01

    Full Text Available In Latvia, the number of aging employees suffering from sleep disorders caused by job stress and poor sleep hygiene is increasing. The non-pharmacologic and pharmacologic treatment is prescribed for these employees in the sleep management. The aim of this research is to clarify the efficiency of using psychotherapy with learning and observing sleep hygiene, combined with the melatonergic drug during a six-week treatment course applied to 25 both male and female intellectual workers over 65 years suffering from insomnia caused by job stress. For the patients representing Group “A” cognitive hypnotherapy, intervention for improving coping with job stress and usage of the melatonergic drug was prescribed, while Group “B” patients received six weeks only drug. The severity of depressive episodes in employees was measured by Montgomery- Åsberg Depression Rating Scale, the level of anxiety was assessed by use Rosenberg Self-Esteem Scale. The results of the research show that insomnia patterns disappeared for 75% of women and 80% of men employees in Group A, but in Group B individuals, – only for 20% of women employees. The results acquired let concluding that the six-week treatment – cognitive hypnotherapy combined with melatonergic drug – is an effective treatment for aging workers suffering from sleep disorders.

  4. Stress Levels of Agricultural Science Cooperating Teachers and Student Teachers: A Repeated Measures Comparative Assessment

    Science.gov (United States)

    McKim, Billy R.; Rayfield, John; Harlin, Julie; Adams, Andy

    2013-01-01

    This study compared job stress levels of Texas agricultural science cooperating teachers and Texas agricultural science student teachers across a semester. The research objectives included describing secondary agricultural science cooperating teachers and student teachers perceptions of stressors, by time of semester (beginning, middle, and end),…

  5. Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats : Effect of interstressor interval length

    NARCIS (Netherlands)

    de Boer, S.F.; Koopmans, S.J.; Slangen, J L; Van der Gugten, J

    1990-01-01

    Plasma noradrenaline (NA), adrenaline (A), corticosterone (CS) and glucose concentrations were determined in blood frequently sampled via a cardiac catheter from freely behaving rats exposed to five successive trials of water-immersion stress (WIS) with an interval between successive trials (interst

  6. Environmental heat stress modulates thyroid status and its response to repeated endotoxin (LPS) challenge in steers

    Science.gov (United States)

    Thyroid hormones are important in the adaptation to heat stress, allowing the adjustment of metabolic rates in favor of decreased energy utilization and heat production. Thyroid status is compromised in a variety of acute and chronic infections and toxin-mediated disease states. Our objective was to...

  7. Repeated measures of inflammation and oxidative stress biomarkers in preeclamptic and normotensive pregnancies.

    Science.gov (United States)

    Ferguson, Kelly K; Meeker, John D; McElrath, Thomas F; Mukherjee, Bhramar; Cantonwine, David E

    2017-05-01

    Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically present when remodeling has failed to occur. Hypotheses surrounding the "second hit" that is necessary for the clinical presentation of the disease focus on maternal inflammation and oxidative stress. Yet, the studies to date that have investigated these factors have used cross-sectional study designs or small study populations. In the present study, we sought to explore longitudinal trajectories, beginning early in gestation, of a panel of inflammation and oxidative stress markers in women who went on to have preeclamptic or normotensive pregnancies. We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which included 50 mothers who experienced preeclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein, the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia diagnosis in association with biomarker concentrations at each of the 4 study visits. In adjusted models, hazard ratios of preeclampsia were significantly (Pinflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker). Hazard ratios at this time point were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for

  8. Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy.

    Science.gov (United States)

    Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J; McElrath, Thomas F; Meeker, John D; Mukherjee, Bhramar

    2017-03-01

    Mediation analysis is useful for understanding mechanisms and has been used minimally in the study of the environment and disease. We examined mediation of the association between phthalate exposure during pregnancy and preterm birth by oxidative stress. This nested case-control study of preterm birth (n = 130 cases, 352 controls) included women who delivered in Boston, Massachusestts, from 2006 through 2008. Phthalate metabolites and 8-isoprostane, an oxidative stress biomarker, were measured in urine from three visits in pregnancy. We applied four counterfactual mediation methods: method 1, utilizing exposure and mediator averages; method 2, using averages but allowing for an exposure-mediator interaction; method 3, incorporating longitudinal measurements of the exposure and mediator; and method 4, using longitudinal measurements and allowing for an exposure-mediator interaction. We observed mediation of the associations between phthalate metabolites and all preterm birth by 8-isoprostane, with the greatest estimated proportion mediated observed for spontaneous preterm births specifically. Fully utilizing repeated measures of the exposure and mediator improved precision of indirect (i.e., mediated) effect estimates, and including an exposure-mediator interaction increased the estimated proportion mediated. For example, for mono(2-ethyl-carboxy-propyl) phthalate (MECPP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), the percent of the total effect mediated by 8-isoprostane increased from 47% to 60% with inclusion of an exposure-mediator interaction term, in reference to a total adjusted odds ratio of 1.67 or 1.48, respectively. This demonstrates mediation of the phthalate-preterm birth relationship by oxidative stress, and the utility of complex regression models in capturing mediated associations when repeated measures of exposure and mediator are available and an exposure-mediator interaction may exist. Citation: Ferguson KK, Chen YH, VanderWeele TJ, Mc

  9. Experimental stress does not increase fluctuating asymmetry of broiler chickens at slaughter age.

    Science.gov (United States)

    Van Poucke, E; Van Nuffel, A; Van Dongen, S; Sonck, B; Lens, L; Tuyttens, F A M

    2007-10-01

    Fluctuating asymmetry (FA) is increasingly applied as a putative indicator of animal welfare. Yet its sensitivity to measure welfare of ad libitum-fed farm animals (that presumably have little or no energy allocation constraints) remains largely untested. This study was conducted to examine whether FA is sensitive to experimentally induced stress in broiler chickens and whether effect sizes differ between emotional and physical stressors. Broiler chickens were randomly assigned to emotional stress treatments (pain or frustration), physical stress treatments (wet litter or high temperature and density), or no stress treatment (control). Both physical stressors, unlike the emotional stressors, were known to affect a number of conventional welfare indicators measured at slaughter age. Left-right asymmetry of 14 bilateral traits was measured at slaughter age and compared between treatments. Seven of the 14 bilateral traits proved unsuitable for the study of FA, either due to the presence of directional asymmetry or high measurement error. Fluctuating asymmetry tended to be lowest in the control group and highest in the high temperature and density treatment. However, either when modeling traits as repeated measures at individual broiler level or when performing trait-by-trait analysis, no significant differences between treatments were detected. This negative result may indicate that FA is not a suitable indicator to detect variations of welfare status in fast-growing broiler chickens because of strong past selection for increased BW and improved feed efficiency, which can mask additional stress effects on developmental processes. Alternatively, FA is not a sensitive indicator of welfare in ad libitum-fed animals because of absence of energy allocation constraints. Finally, FA may still be a suitable indicator of welfare under such conditions, but differences between treatments may remain undetected due to insufficient statistical power, which was estimated at 35% for

  10. Modulatory influence of rarely repeated of immobilization episodes on the interleukin-1β-dependent reaction of blood leukocytes and hepatoprotective effect of restraint stress.

    Science.gov (United States)

    Tseilikman, O B; Tseilikman, V E; Linin, A V; Gubkin, D A; Rudina, E A; Trubetskoy, S A; Ivanov, P V; Pozdnyakov, E A

    2011-02-01

    Repeated episodes of 1-h restraint stress were accompanied by a decrease in the sensitivity of blood leukocytes and cytochrome P450-dependent monooxygenases of the liver to recombinant IL-1β. These changes are associated with the anti-inflammatory hepatoprotective effect of chronic stress.

  11. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

    NARCIS (Netherlands)

    Boks, Marco P.; van Mierlo, Hans C.; Rutten, Bart P. F.; Radstake, Timothy R. D. J.; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C.; Vinkers, Christiaan H.; Broen, Jasper C. A.; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methyla

  12. Salivary Alpha Amylase Activity in Human Beings of Different Age Groups Subjected to Psychological Stress

    National Research Council Canada - National Science Library

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-01-01

    ... in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip...

  13. Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function.

    Science.gov (United States)

    OBJECTIVE: Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and i...

  14. Electric signal emissions during repeated abrupt uniaxial compressional stress steps in amphibolite from KTB drilling

    Directory of Open Access Journals (Sweden)

    D. Triantis

    2007-01-01

    Full Text Available Laboratory experiments have confirmed that the application of uniaxial stress on rock samples is accompanied by the production of weak electric currents, to which the term Pressure Stimulated Currents – PSC has been attributed. In this work the PSC emissions in amphibolite samples from KTB drilling are presented and commented upon. After having applied sequential loading and unloading cycles on the amphibolite samples, it was ascertained that in every new loading cycle after unloading, the emitted PSC exhibits lower peaks. This attitude of the current peaks is consistent with the acoustic emissions phenomena, and in this work is verified for PSC emissions during loading – unloading procedures. Consequently, the evaluation of such signals can help to correlate the state and the remaining strength of the sample with respect to the history of its mechanical stress.

  15. Effects of Repeated Acute Stress in Obese and Non-Obese Rats

    Science.gov (United States)

    2008-04-02

    levels in the body. The effects of a dysregulated stress responses and, in particular, elevated cortisol levels are evident in the brain and...has a mutated leptin receptor gene (Duclos et aI., 2005). This gene produces the hormone leptin which is expressed in adipose tissue (Kandel...and to greater adipose tissue in diet-induced obese rats (Levin & Dunn-Meynell, 2000). Other methods to induce obesity in animals include I IU t

  16. The Role of Oxidative Stress in the Aging Process

    Directory of Open Access Journals (Sweden)

    Barbara F. Oliveira

    2010-01-01

    Full Text Available The aging of organisms is characterized by a gradual functional decline of all organ systems. An appropriate theory must explain four main characteristics of aging: it is progressive, endogenous, irreversible, and deleterious for the individual. The aging of the immune system, or immunosenescence, is manifested by an increased susceptibility to infections with increased morbidity and mortality. Phagocytic capacity, synthesis of reactive oxygen intermediaries, and the intracellular killing efficiency of neutrophils are impaired in the elderly. Among all aging theories, the most updated one describes the free radicals. It implies that progressive aging is associated with higher levels of oxidative biomolecules reacted with free radicals. Although reactive oxygen species (ROS are predominantly implicated in causing cell damage, they also play a major physiological role in several aspects of intracellular signaling and regulation. ROS include a number of chemically reactive molecules derived from oxygen. Not only oxygen, but also nitrogen can be deleterious species. The overproduction of reactive nitrogen species (RNS is called nitrosative stress. ROS/RNS are known to play a dual role in biological systems since they can be either harmful or beneficial to living systems.

  17. Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

    Science.gov (United States)

    Martens, Dries S; Nawrot, Tim S

    2016-09-01

    Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies.

  18. Stress appraisals and cellular aging: a key role for anticipatory threat in the relationship between psychological stress and telomere length.

    Science.gov (United States)

    O'Donovan, Aoife; Tomiyama, A Janet; Lin, Jue; Puterman, Eli; Adler, Nancy E; Kemeny, Margaret; Wolkowitz, Owen M; Blackburn, Elizabeth H; Epel, Elissa S

    2012-05-01

    Chronic psychological stress is a risk factor for multiple diseases of aging. Accelerated cellular aging as indexed by short telomere length has emerged as a potential common biological mechanism linking various forms of psychological stress and diseases of aging. Stress appraisals determine the degree and type of biological stress responses and altered stress appraisals may be a common psychological mechanism linking psychological stress and diseases of aging. However, no previous studies have examined the relationship between stress appraisals and telomere length. We exposed chronically stressed female caregivers and non-caregiving controls (N=50; M age=62.14±6.10) to a standardized acute laboratory stressor and measured their anticipatory and retrospective threat and challenge appraisals of the stressor. We hypothesized that threat and challenge appraisals would be associated with shorter and longer telomere length respectively, and that chronic caregiving stress would influence telomere length through altered stress appraisals. Higher anticipatory threat appraisals were associated with shorter age-adjusted telomere length (β=-.32, p=.03), but challenge appraisals and retrospective threat appraisals showed no independent association with telomere length. Caregivers reported significantly higher anticipatory (β=-.36, p=.006) and retrospective (β=-.29, p=.03) threat appraisals than controls, but similar challenge appraisals. Although there was no significant main effect of caregiver status on telomere length, caregiving had a significant indirect effect on telomere length through anticipatory threat appraisals. Exaggerated anticipatory threat appraisals may be a common and modifiable psychological mechanism of psychological stress effects on cellular aging.

  19. Central serotonin depletion modulates the behavioural, endocrine and physiological responses to repeated social stress and subsequent c-fos expression in the brains of male rats.

    Science.gov (United States)

    Chung, K K; Martinez, M; Herbert, J

    1999-01-01

    Intraspecific confrontation has been used to study effect of depleting central serotonin on the adaptation of male rats to repeated social stress (social defeat). Four groups of adult male rats were used (serotonin depletion/sham: stressed; serotonin depletion/sham: non-stressed). Central serotonin was reduced (by 59-97%) by a single infusion of the neurotoxin 5,7-dihydroxtryptamine (150 microg) into the cerebral ventricles; levels of dopamine and noradrenaline were unaltered (rats received appropriate uptake blockers prior to neurotoxic infusions). Sham-operated animals received solute only. Rats were then either exposed daily for 10 days to a second larger aggressive male in the latter's home cage, or simply transferred to an empty cage (control procedure). Rats with reduced serotonin failed to show the increased freezing behaviour during the pre-defeat phase of the social interaction test characteristic of sham animals. There was no change in the residents' behaviour. Core temperature increased during aggressive interaction in sham rats, and this did not adapt with repeated stress. By contrast, stress-induced hyperthermia was accentuated in serotonin-reduced rats as the number of defeat sessions increased. Basal core temperature was unaffected by serotonin depletion. Heart rate increased during social defeat, but this did not adapt with repeated stress; serotonin depletion had no effect on this cardiovascular response. Basal corticosterone was increased in serotonin-depleted rats, but the progressive reduction in stress response over days was not altered. C-fos expression in the brain was not altered in control (non-stressed) rats by serotonin reduction in the areas examined, but there was increased expression after repeated social stress in the medial amygdala of 5-HT depleted rats. These experiments show that reduction of serotonin alters responses to repeated social stress in male rats, and suggests a role for serotonin in the adaptive process.

  20. Iron accumulation with age, oxidative stress and functional decline.

    Directory of Open Access Journals (Sweden)

    Jinze Xu

    Full Text Available Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength in male Fischer 344 X Brown Norway rats fed ad libitum (AL or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects.

  1. Stress Relaxation Behavior and Springback Equation of 7050 Aluminum Alloys During Age-forming Process

    Directory of Open Access Journals (Sweden)

    REN Wei-wei

    2016-09-01

    Full Text Available The stress relaxation behavior and springback equation of 7050 aluminum alloys during the age-forming process were studied through self-designed uniaxial tension device. The results show that in traditional aging temperature, the stress relaxation curve of 7050 aluminum alloys exhibits a classical logarithmic decrement curve. The stress relaxation process can be divided into three stages, which are the initial stress decayed fast stage, the subsequent stress slowly decayed stage and the stress constantly maintained stage, respectively. Stress relaxation limit of 7050 aluminum alloys decreases with increasing aging temperature. The threshold stress presents during the stress relaxation process due to the interaction between precipitation behavior and dislocation creep of 7050 aluminum alloys. The stress relaxation equation of 7050 aluminum alloys is obtained through resolving the feature and Taylor equation of relaxation process, and using the stress relaxation equation can precisely predict the springback of workpiece after age-forming.

  2. Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

    Directory of Open Access Journals (Sweden)

    Mukae Takehiro

    2011-09-01

    Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

  3. Loss of Sustained Activity in the Ventromedial Prefrontal Cortex in Response to Repeated Stress in Individuals with Early-Life Emotional Abuse: Implications for Depression Vulnerability

    Directory of Open Access Journals (Sweden)

    Lihong eWang

    2013-06-01

    Full Text Available Repeated psychosocial stress in early life has significant impact on both behavior and neural function which, together, increase vulnerability to depression. However, neural mechanisms related to repeated stress remain unclear. We hypothesize that early-life stress may result in a reduced capacity for cognitive control in response to a repeated stressor, particularly in individuals who developed maladaptive emotional processing strategies, namely trait rumination. Individuals who encountered early-life stress but have adaptive emotional processing, namely trait mindfulness, may demonstrate an opposite pattern. Using a mental arithmetic task to induce mild stress and a mindful breathing task to induce a mindful state, we tested this hypothesis by examining blood perfusion changes over time in healthy young men. We found that subjects with early-life stress, particularly emotional abuse, failed to sustain neural activation in the orbitofrontal and ventromedial prefrontal cortex (vmPFC over time. Given that the vmPFC is known to regulate amygdala activity during emotional processing, we subsequently compared the perfusion in the vmPFC and the amygdala in depression-vulnerable (having early life stress and high in rumination and resilient (having early life stress and high in mindfulness subjects. We found that depression-vulnerable subjects had increased amygdala perfusion and reduced vmPFC perfusion during the later runs than that during the earlier stressful task runs. In contrast, depression resilient individuals showed the reverse pattern. Our results indicate that the vmPFC of depression-vulnerable subjects may have a limited capacity to inhibit amygdala activation to repeated stress over time, whereas the vmPFC in resilient individuals may adapt to stress quickly. This pilot study warrants future investigation to clarify the stress-related neural activity pattern dynamically to identify depression vulnerability at an individual level.

  4. Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth.

    Science.gov (United States)

    Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu; Loch-Caruso, Rita; Mukherjee, Bhramar; Meeker, John D

    2015-02-01

    The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth. This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation. Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy. Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles.

    Science.gov (United States)

    Suzuki, Kazushi; Zhou, Jiayi; Sato, Toshiya; Takao, Keizo; Miyagawa, Tsuyoshi; Oyake, Mutsuo; Yamada, Mitunori; Takahashi, Hitoshi; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

    2012-05-01

    Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant progressive neurodegenerative disorder with intellectual deterioration and various motor deficits including ataxia, choreoathetosis, and myoclonus, caused by an abnormal expansion of CAG repeats in the DRPLA gene. Longer expanded CAG repeats contribute to an earlier age of onset, faster progression, and more severe neurological symptoms in DRPLA patients. In this study, we have established DRPLA transgenic mouse lines (sublines) harboring a single copy of the full-length mutant human DRPLA gene carrying various lengths of expanded CAG repeats (Q76, Q96, Q113, and Q129), which have clearly shown motor deficits and memory disturbance whose severity increases with the length of expanded CAG repeats and age, and successfully replicated the CAG repeat length- and age-dependent features of DRPLA patients. Neuronal intranuclear accumulation of the mutant DRPLA protein has been suggested to cause transcriptional dysregulation, leading to alteration in gene expression and neuronal dysfunction. In this study, we have conducted a comprehensive analysis of gene expression profiles in the cerebrum and cerebellum of transgenic mouse lines at 4, 8, and 12 weeks using multiple microarray platforms, and demonstrated that both the number and expression levels of the altered genes are highly dependent on CAG repeat length and age in both brain regions. Specific groups of genes and their function categories were identified by further agglomerative cluster analysis and gene functional annotation analysis. Calcium signaling and neuropeptide signaling, among others, were implicated in the pathophysiology of DRPLA. Our study provides unprecedented CAG-repeat-length-dependent mouse models of DRPLA, which are highly valuable not only for elucidating the CAG-repeat-length-dependent pathophysiology of DRPLA but also for developing therapeutic strategies for DRPLA.

  6. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    Science.gov (United States)

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

  7. Telomere dynamics may link stress exposure and ageing across generations.

    Science.gov (United States)

    Haussmann, Mark F; Heidinger, Britt J

    2015-11-01

    Although exposure to stressors is known to increase disease susceptibility and accelerate ageing, evidence is accumulating that these effects can span more than one generation. Stressors experienced by parents have been reported to negatively influence the longevity of their offspring and even grand offspring. The mechanisms underlying these long-term, cross-generational effects are still poorly understood, but we argue here that telomere dynamics are likely to play an important role. In this review, we begin by surveying the current connections between stress and telomere dynamics. We then lay out the evidence that exposure to stressors in the parental generation influences telomere dynamics in offspring and potentially subsequent generations. We focus on evidence in mammalian and avian studies and highlight several promising areas where our understanding is incomplete and future investigations are critically needed. Understanding the mechanisms that link stress exposure across generations requires interdisciplinary studies and is essential to both the biomedical community seeking to understand how early adversity impacts health span and evolutionary ecologists interested in how changing environmental conditions are likely to influence age-structured population dynamics.

  8. Repeated Thermal Stress, Shading, and Directional Selection in the Florida Reef Tract

    Directory of Open Access Journals (Sweden)

    Robert van Woesik

    2017-06-01

    Full Text Available Over the last three decades reef corals have been subjected to an unprecedented frequency and intensity of thermal-stress events, which have led to extensive coral bleaching, disease, and mortality. Over the next century, the climate is predicted to drive sea-surface temperatures to even higher levels, consequently increasing the risk of mass bleaching and disease outbreaks. Yet, there is considerable temporal and spatial variation in coral bleaching and in disease prevalence. Using data collected from 2,398 sites along the Florida reef tract from 2005 to 2015, this study examined the temporal and spatial patterns of coral bleaching and disease in relation to coral-colony size, depth, temperature, and chlorophyll-a concentrations. The results show that coral bleaching was most prevalent during the warmest years in 2014 and 2015, and disease was also most prevalent in 2010, 2014, and 2015. Although the majority of the corals surveyed were found in habitats with low chlorophyll-a concentrations, and high irradiance, these same habitats showed the highest prevalence of coral bleaching and disease outbreaks during thermal-stress events. These results suggest that directional selection in a warming ocean may favor corals able to tolerate inshore, shaded environments with high turbidity and productivity.

  9. Oxidative stress and its downstream signaling in aging eyes

    Directory of Open Access Journals (Sweden)

    Pinazo-Durán MD

    2014-04-01

    Full Text Available María Dolores Pinazo-Durán,1,* Roberto Gallego-Pinazo,2,* Jose Javier García-Medina,1,3,* Vicente Zanón-Moreno,1,4 Carlo Nucci,5 Rosa Dolz-Marco,2 Sebastián Martínez-Castillo,2 Carmen Galbis-Estrada,1 Carla Marco-Ramírez,1 Maria Isabel López-Gálvez,6,* David J Galarreta,6,* Manuel Díaz-Llópis4,*1Ophthalmic Research Unit "Santiago Grisolía", Valencia, Spain; 2Department of Ophthalmology, Macula Section, The University and Polytechnic Hospital La Fe, Valencia, Spain; 3Department of Ophthalmology, University Hospital Reina Sofia, Murcia, Spain; 4Faculty of Medicine, University of Valencia, Spain; 5University of Rome Tor Vergata, Rome, Italy; 6Instituto de Oftalmobiología Aplicada (IOBA, Valladolid, Spain *Members of the Spanish Net of Ocular Pathology of the Instituto de Salud Carlos III (Madrid, OFTAREDBackground: Oxidative stress (OS and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS production and the ability of the antioxidant (AOX biological systems to fight against oxidative injury.Objective: We reviewed the role of OS and its downstream signaling in aging eyes.Methods: A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy.Results: Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed.Conclusion: OS, nutritional status, and nutraceutic supplements have

  10. Response to stress in Drosophila is mediated by gender, age and stress paradigm.

    Science.gov (United States)

    Neckameyer, Wendi S; Nieto-Romero, Andres R

    2015-01-01

    All living organisms must maintain equilibrium in response to internal and external challenges within their environment. Changes in neural plasticity (alterations in neuronal populations, dendritic remodeling, and synaptic turnover) are critical components of the homeostatic response to stress, which has been strongly implicated in the onset of affective disorders. However, stress is differentially perceived depending on the type of stress and its context, as well as genetic background, age and sex; therefore, an individual's maintenance of neuronal homeostasis must differ depending upon these variables. We established Drosophila as a model to analyze homeostatic responses to stress. Sexually immature and mature females and males from an isogenic wild-type strain raised under controlled environmental conditions were exposed to four reproducible and high-throughput translatable stressors to facilitate the analysis of a large number of animals for direct comparisons. These animals were assessed in an open-field arena, in a light-dark box, and in a forced swim test, as well as for sensitivity to the sedative effects of ethanol. These studies establish that immature and mature females and males represent behaviorally distinct populations under control conditions as well as after exposure to different stressors. Therefore, the neural substrates mediating the stress response must be differentially expressed depending upon the hormonal status of the brain. In addition, an adaptive response to a given stressor in one paradigm was not predictive for outcomes in other paradigms.

  11. Neonatal pain-related stress predicts cortical thickness at age 7 years in children born very preterm.

    Directory of Open Access Journals (Sweden)

    Manon Ranger

    Full Text Available BACKGROUND: Altered brain development is evident in children born very preterm (24-32 weeks gestational age, including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity is associated with altered cortical thickness in very preterm children at school age. METHODS: 42 right-handed children born very preterm (24-32 weeks gestational age followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure, was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. RESULTS: After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014, predominately in the frontal and parietal lobes. CONCLUSIONS: In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress

  12. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age.

    Science.gov (United States)

    Doesburg, Sam M; Chau, Cecil M; Cheung, Teresa P L; Moiseev, Alexander; Ribary, Urs; Herdman, Anthony T; Miller, Steven P; Cepeda, Ivan L; Synnes, Anne; Grunau, Ruth E

    2013-10-01

    Children born very prematurely (neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain-related stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children.

  13. Physical exercise affects the epigenetic programming of rat brain and modulates the adaptive response evoked by repeated restraint stress.

    Science.gov (United States)

    Kashimoto, R K; Toffoli, L V; Manfredo, M H F; Volpini, V L; Martins-Pinge, M C; Pelosi, G G; Gomes, M V

    2016-01-01

    Epigenetics has recently been linked to molecular adaptive responses evoked by physical exercise and stress. Herein we evaluated the effects of physical exercise on global DNA methylation and expression of the Dnmt1 gene in the rat brain and also verified its potential to modulate responses evoked by repeated restraint stress (RRS). Wistar rats were classified into the following experimental groups: (1) physically active (EX): animals submitted to swimming during postnatal days 53-78 (PND); (2) stress (ST): animals submitted to RRS during 75-79PND; (3) exercise-stress (EX-ST): animals submitted to swimming during 53-78PND and to RRS during 75-79PND, and (4) control (CTL): animals that were not submitted to intervention. Samples from the hippocampus, cortex and hypothalamus were obtained at 79PND. The global DNA methylation profile was assessed using an ELISA-based method and the expression of Dnmt1 was evaluated by real-time PCR. Significantly increased methylation was observed in the hypothalamus of animals from the EX group in comparison to CTL. Comparative analysis involving the EX-ST and ST groups revealed increased global DNA methylation in the hippocampus, cortex, and hypothalamus of EX-ST, indicating the potential of physical exercise in modulating the responses evoked by RRS. Furthermore, decreased expression of the Dnmt1 gene was observed in the hippocampus and hypothalamus of animals from the EX-ST group. In summary, our data indicate that physical exercise affects DNA methylation of the hypothalamus and might modulate epigenetic responses evoked by RRS in the hippocampus, cortex, and hypothalamus. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Corticosterone stress response shows long-term repeatability and links to personality in free-living Nazca boobies.

    Science.gov (United States)

    Grace, Jacquelyn K; Anderson, David J

    2014-11-01

    The concept of "coping styles", or consistently different responses to stressors, is of broad interest in behavioral ecology and biomedicine. Two critical predictions of this concept are individual consistency of neurophysiological and behavioral responses (relative to population variability) and a negative relationship between aggression/proactivity and hypothalamic-pituitary-adrenal axis reactivity. Recent studies failed to provide strong support for these predictions, especially outside of strictly controlled conditions, and long-term measures to test the first prediction are rare. Here, we demonstrate individual repeatability across 2-3years of maximum circulating corticosterone concentration [CORT] and area under the [CORT] response curve (AUCI) during a standard capture-restraint test in wild, free-living adult Nazca boobies (Sula granti). We also show that the stress response predicts the personality traits aggression and anxiety in these birds (measured in the wild); however, the strength of these results was weak. Maximum [CORT] and AUCI showed higher repeatability between years than baseline [CORT]. After controlling breeding status, sex, mass, date sampled, and their interactions, baseline [CORT] was most closely related to personality traits, followed by AUCI, and then maximum [CORT]. The direction of these relationships depended on whether the testing context was social or non-social. [CORT] parameters had little to no relationship with cross-context plasticity in personality traits. Our results generally affirm two critical predictions of coping styles, but match the emerging trend that these relationships are weak in the wild, and may depend on testing context.

  15. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

    Energy Technology Data Exchange (ETDEWEB)

    López-Arnau, Raúl; Martínez-Clemente, José [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Rodrigo, Teresa [Animal Experimentation Unit of Psychology and Pharmacy, University of Barcelona (Spain); Pubill, David [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Camarasa, Jorge, E-mail: jcamarasa@ub.edu [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain); Escubedo, Elena [Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Faculty of Pharmacy, University of Barcelona (Spain); Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona (Spain)

    2015-07-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3 × 25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26 ± 2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D{sub 2} dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone. - Highlights: • We studied the dopaminergic and serotonergic neurotoxicity of mephedrone in rats. • Mephedrone induced a transient hypothermia following sustained hyperthermia. • In a weekend consumption pattern, mephedrone induced selective neurotoxicity. • Mephedrone generated oxidative stress. • Mephedrone induced an impairment in memory function.

  16. Case study: videogame distraction reduces behavioral distress in a preschool-aged child undergoing repeated burn dressing changes: a single-subject design

    National Research Council Canada - National Science Library

    Sil, Soumitri; Dahlquist, Lynnda M; Burns, Andrew J

    2013-01-01

    This single-subject design study evaluated the feasibility and efficacy of passive and interactive videogame distraction on behavioral distress for a preschool-aged child receiving repeated burn dressing changes...

  17. Montmorency cherries reduce the oxidative stress and inflammatory responses to repeated days high-intensity stochastic cycling.

    Science.gov (United States)

    Bell, Phillip G; Walshe, Ian H; Davison, Gareth W; Stevenson, Emma; Howatson, Glyn

    2014-02-21

    This investigation examined the impact of Montmorency tart cherry concentrate (MC) on physiological indices of oxidative stress, inflammation and muscle damage across 3 days simulated road cycle racing. Trained cyclists (n = 16) were divided into equal groups and consumed 30 mL of MC or placebo (PLA), twice per day for seven consecutive days. A simulated, high-intensity, stochastic road cycling trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and inflammation were measured from blood samples collected at baseline and immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid hydroperoxides (LOOH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), interleukin-1-beta (IL-1-β), high-sensitivity C-reactive protein (hsCRP) and creatine kinase (CK) were conducted. LOOH (p < 0.01), IL-6 (p < 0.05) and hsCRP (p < 0.05) responses to trials were lower in the MC group versus PLA. No group or interaction effects were found for the other markers. The attenuated oxidative and inflammatory responses suggest MC may be efficacious in combating post-exercise oxidative and inflammatory cascades that can contribute to cellular disruption. Additionally, we demonstrate direct application for MC in repeated days cycling and conceivably other sporting scenario's where back-to-back performances are required.

  18. Montmorency Cherries Reduce the Oxidative Stress and Inflammatory Responses to Repeated Days High-Intensity Stochastic Cycling

    Directory of Open Access Journals (Sweden)

    Phillip G. Bell

    2014-02-01

    Full Text Available This investigation examined the impact of Montmorency tart cherry concentrate (MC on physiological indices of oxidative stress, inflammation and muscle damage across 3 days simulated road cycle racing. Trained cyclists (n = 16 were divided into equal groups and consumed 30 mL of MC or placebo (PLA, twice per day for seven consecutive days. A simulated, high-intensity, stochastic road cycling trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and inflammation were measured from blood samples collected at baseline and immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid hydroperoxides (LOOH, interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, interleukin-8 (IL-8, interleukin-1-beta (IL-1-β, high-sensitivity C-reactive protein (hsCRP and creatine kinase (CK were conducted. LOOH (p < 0.01, IL-6 (p < 0.05 and hsCRP (p < 0.05 responses to trials were lower in the MC group versus PLA. No group or interaction effects were found for the other markers. The attenuated oxidative and inflammatory responses suggest MC may be efficacious in combating post-exercise oxidative and inflammatory cascades that can contribute to cellular disruption. Additionally, we demonstrate direct application for MC in repeated days cycling and conceivably other sporting scenario’s where back-to-back performances are required.

  19. De novo characterization of the Dialeurodes citri transcriptome: mining genes involved in stress resistance and simple sequence repeats (SSRs) discovery.

    Science.gov (United States)

    Chen, E-H; Wei, D-D; Shen, G-M; Yuan, G-R; Bai, P-P; Wang, J-J

    2014-02-01

    The citrus whitefly, Dialeurodes citri (Ashmead), is one of the three economically important whitefly species that infest citrus plants around the world; however, limited genetic research has been focused on D. citri, partly because of lack of genomic resources. In this study, we performed de novo assembly of a transcriptome using Illumina paired-end sequencing technology (Illumina Inc., San Diego, CA, USA). In total, 36,766 unigenes with a mean length of 497 bp were identified. Of these unigenes, we identified 17,788 matched known proteins in the National Center for Biotechnology Information database, as determined by Blast search, with 5731, 4850 and 14,441 unigenes assigned to clusters of orthologous groups (COG), gene ontology (GO), and SwissProt, respectively. In total, 7507 unigenes were assigned to 308 known pathways. In-depth analysis of the data showed that 117 unigenes were identified as potentially involved in the detoxification of xenobiotics and 67 heat shock protein (Hsp) genes were associated with environmental stress. In addition, these enzymes were searched against the GO and COG database, and the results showed that the three major detoxification enzymes and Hsps were classified into 18 and 3, 6, and 8 annotations, respectively. In addition, 149 simple sequence repeats were detected. The results facilitate the investigation of molecular resistance mechanisms to insecticides and environmental stress, and contribute to molecular marker development. The findings greatly improve our genetic understanding of D. citri, and lay the foundation for future functional genomics studies on this species.

  20. Comparative Research of Oil-paper Aging Characteristics Under Thermal Stress and Combined Thermo-electrical Stresses

    Institute of Scientific and Technical Information of China (English)

    WANG Shi-qiang; WU Feng-jiao; XU Hao; ZHANG Guan-jun

    2011-01-01

    During the operation of power transformer, its oil-paper insulation is continuously subjected to various stresses, e. g. , the thermal, electrical, mechanical, and chemical stresses, which cause insulation aging gradually. It has been considered that the combined thermal and electrical stresses are the most important and unavoidable factors that induce insulation materials aging. In this work, accelerated aging experiments of oil-impregnated pressboards un der combined thermal (130℃) and electrical stresses (4 kV/mm) are performed, while the aging experiments under single thermal stress are also carried out at the corresponding temperature (130 ℃). The electrical and physic-chemical properties of oil, including dielectric losses factor tanδ resistivity, acid value and pH value etc. , are measured during the aging process. Dissolved gasses in oil and polymerization degree of cellulose are also measured. The relationship between these properties of oil-paper insulation and aging time is investigated. The results show that dissolved gases in oil, resistivity, tanδ of oil under combined thermal and electrical stresses are obviously different from that under thermal stress during aging process while some other properties show similar changing :trend. For cellulose, compared with the single thermal aging results, it even shows a slower degradation rate in the presence of elec trical stress.

  1. Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone.

    Science.gov (United States)

    López-Arnau, Raúl; Martínez-Clemente, José; Rodrigo, Teresa; Pubill, David; Camarasa, Jorge; Escubedo, Elena

    2015-07-01

    Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3×25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26±2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D2 dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone.

  2. Effects of stress and physical ageing on nonlinear creep behavior of poly(methyl methacrylate)

    Institute of Scientific and Technical Information of China (English)

    赵荣国; 陈朝中; 李其抚; 罗文波

    2008-01-01

    The effects of stress,ageing time and ageing temperature on creep behavior of poly(methyl methacrylate) were studied.After annealing above its glass transition temperature for a period of time to eliminate the stress and thermal history,the specimens were quenched and aged at various ageing temperatures for different ageing time,and then the short-term creep tests under different stress levels were carried out at room temperature.The creep strains were modeled by means of time-ageing time equivalence and time-stress equivalence,and the master creep curves were constructed via ageing time shift factors and stress shift factors.The results indicate that the creep rate increases with stress,while decreases with ageing time,and the ageing temperature history obviously affects the creep rate.For linear viscoelastic material,the ageing shift rate is independent on imposed stress,while for nonlinear viscoelastic material,the ageing shift rate decreases with increasing stress.The unified master creep curve up to 540 d at reference state was constructed by shifting the creep curves horizontally along the logarithmic time axis to overlap each other.It is demonstrated that the time-stress equivalence,united with the time-ageing time equivalence,provides an effective accelerated characterization technique in the laboratory to evaluate the long-term creep behavior of physical ageing polymers.

  3. Environmental heat stress modulates thyroid status and its response to repeated endotoxin challenge in steers.

    Science.gov (United States)

    Kahl, S; Elsasser, T H; Rhoads, R P; Collier, R J; Baumgard, L H

    2015-07-01

    The objective of this study was to evaluate in cattle, the effects of acute exposure to a heat stress (HS) environment on the status of the pituitary (thyrotropin, TSH)-thyroid (thyroxine, T4)-peripheral tissue T4 deiodination (type 1 5'-deiodinase [D1]; triiodothyronine [T3]; reverse-triiodothyronine [rT3]) axis, and the further response of this pituitary-thyroid-peripheral tissue axis (PTTA) to perturbation caused by the induction of the proinflammatory innate immune state provoked by the administration of gram-negative bacteria endotoxin (lipopolysaccharide [LPS]). Ten steers (318 ± 49 kg body weight) housed in controlled environment chambers were subjected to either a thermoneutral (TN: constant 19°C) or HS temperature conditions (cyclical daily temperatures: 32.2°C-40.0°C) for a total period of 9 d. To minimize the effects of altered plane of nutrition due to HS, steers in TN were pair-fed to animals in HS conditions. Steers received 2 LPS challenges 3 d apart (LPS1 and LPS2; 0.2 μg/kg body weight, intravenously, Escherichia coli 055:B5) with the first challenge administered on day 4 relative to the start of the environmental conditioning. Jugular blood samples were collected at 0, 1, 2, 4, 7, and 24 h relative to the start of each LPS challenge. Plasma TSH, T4, T3, and rT3 were measured by radioimmunoassay. Liver D1 activity was measured in biopsy samples collected before the LPS1 (0 h) and 24 h after LPS2. Before the start of LPS1, HS decreased (P thyroid components of the PTTA, whereas a normal capacity to generate T3 from T4 in the liver is preserved. The data also suggest that LPS challenge further suppresses all components of the PTTA including liver T3 generation, and these PTTA perturbations are more pronounced in steers that encounter a HS exposure. Published by Elsevier Inc.

  4. The Brief Repeatable Battery: psychometrics and normative values with age, education and gender corrections in a Serbian population.

    Science.gov (United States)

    Obradovic, D; Petrovic, M; Antanasijevic, I; Marinkovic, J; Stojanovic, T; Obradovic, S

    2012-12-01

    Cognitive impairment is present in up to 65 % of multiple sclerosis (MS) patients. The Brief Repeatable Battery of neuropsychological tests (BRB) is one of the most used neuropsychological tools for cognitive assessment in MS. However, relative lack of normative data limits its application in research and clinical practice. In order to obtain normative data for a Serbian population, we administered the BRB version A to 140 healthy subjects and assessed the influence of demographic factors such as gender, age, and education on the tests' scores. We also calculated corrections for these factors. Higher education was associated with better performance on all the tests. Age influenced all the tests, except the word list generation, higher age being associated with worse performance on all other tests. Women performed worse on the paced auditory serial addition test 2, no other gender differences were observed. Our data obtained for the Serbian population could further improve use of the BRB in clinical practice and for the research purposes, establishing cognitive evaluation as a part of standard neurological examination of MS patients.

  5. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.

    Science.gov (United States)

    Schiavon, Angélica Pupin; Bonato, Jéssica Mendes; Milani, Humberto; Guimarães, Francisco Silveira; Weffort de Oliveira, Rúbia Maria

    2016-01-04

    Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice.

  6. Do levels of perceived stress increase with increasing age after age 65? A population-based study.

    Science.gov (United States)

    Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

    2015-09-01

    psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

    Science.gov (United States)

    Sambataro, Fabio; Podell, Jamie E; Murty, Vishnu P; Das, Saumitra; Kolachana, Bhaskar; Goldberg, Terry E; Weinberger, Daniel R; Mattay, Venkata S

    2015-08-01

    Dopamine modulation of striatal function is critical for executive functions such as working memory (WM) updating. The dopamine transporter (DAT) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated with DAT expression, such that 9-repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10-repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT1-3'-UTR-VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age-related decrease in striatal activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced striatal activity and increased striatal-hippocampal connectivity during WM updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age-related decline in striatal function is similar across both DAT1-3'-UTR-VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR polymorphism independently modulate striatal function. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  8. Increasing the repeating units of ethylene glycol-based dimethacrylates directed toward reduced oxidative stress and co-stimulatory factors expression in human monocytic cells.

    Science.gov (United States)

    Tamura, Atsushi; Fukumoto, Izumi; Yui, Nobuhiko; Matsumura, Mitsuaki; Miura, Hiroyuki

    2015-03-01

    The ethylene glycol-based dimethacrylates are commonly used in biomaterials and dental restorative materials as a cross-linking agent. In this study, toxic effect of triethylene glycol dimethacrylate (TEGDMA) and poly(ethylene glycol) dimethacrylates (PEG-DMAs) with various ethylene glycol repeating units was investigated in terms of cytotoxicity, oxidative stress, and the expression of co-stimulatory factors in human leukemia cell line (THP-1 cells) to verify the effect of ethylene glycol repeating units. Note that the 1-octanol/water partition coefficient of PEG-based dimethacrylates decreased with increasing the ethylene glycol repeating units, indicating that the hydrophilicity of PEG-DMAs increased with ethylene glycol repeating units. The toxic effect of PEG-DMAs such as cytotoxicity, oxidative stress, and the expression of CD86 in treated THP-1 cells are reduced with increasing the ethylene glycol repeating units in PEG-DMAs. However, the expression of CD54 in treated THP-1 cells was not influenced with the ethylene glycol repeating units and the maximal expression level of CD54 was observed at the concentration range of 2-4 mM for all samples. Accordingly, hydrophilic character of PEG-DMAs with long ethylene glycol chains definitely alleviates the some toxic aspect of PEG-based DMAs. This finding would provide important insight into the design of new biomaterials and dental materials with superior biocompatibility. © 2014 Wiley Periodicals, Inc.

  9. Oxidative stress, innate immunity, and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE. These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD or choroidal neovascularization (CNV, or wet AMD. Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory

  10. Oxidative stress, innate immunity, and age-related macular degeneration.

    Science.gov (United States)

    Shaw, Peter X; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer's disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  11. Age, splanchnic vasoconstriction, and heat stress during tilting

    Science.gov (United States)

    Minson, C. T.; Wladkowski, S. L.; Pawelczyk, J. A.; Kenney, W. L.

    1999-01-01

    During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

  12. Association of Age to Mortality and Repeat Revascularization in End-Stage Renal Disease Patients: Implications for Clinicians and Future Health Policies

    Science.gov (United States)

    Krishnaswami, Ashok; Alloggiamento, Thomas; Forman, Daniel E; Leong, Thomas K; Go, Alan S; McCulloch, Charles E

    2016-01-01

    Background: The clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points. Objective: To assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes. Design: Observational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis. Main Outcome Measures: Primary and secondary outcomes were all-cause mortality and repeat revascularization, respectively. Results: Graphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization. Conclusion: Employing the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level. PMID:26934624

  13. The effects of aging and oxidative stress on psychomotor and cognitive behavior

    OpenAIRE

    Shukitt-Hale, Barbara

    1999-01-01

    Decrements in motor and cognitive function occur in aging, possibly due to oxidative stress-induced damage to the brain. Declines in antioxidant defense mechanisms have been postulated as a causative factor in these age-related decrements, however a clear link between oxidative stress (OS) and behavioral changes in aging has yet to be established. This review shows that age-validated psychomotor and cognitive tests are sensitive to behavioral deficits under different models of OS, including: ...

  14. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

    Science.gov (United States)

    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats.

  15. Family Stress, Perception of Pregnancy, and Age of First Menarche among Pregnant Adolescents.

    Science.gov (United States)

    Ravert, April A; Martin, Jennifer

    1997-01-01

    Examines family-of-origin stress, age of first menarche, and the perceptions of pregnancy as a life event in 97 pregnant adolescents. Participants' reported high levels of family stress with only a moderate level of impact or stress attributed to the pregnancy. As a group, the girls' first menarche matched national averages. (RJM)

  16. Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats.

    Science.gov (United States)

    Nyhuis, Tara J; Masini, Cher V; Taufer, Kirsten L; Day, Heidi E W; Campeau, Serge

    2016-01-01

    The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress.

  17. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    2016-01-01

    OBJECTIVE: The prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were investigat

  18. The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter.

    Science.gov (United States)

    Gijselinck, I; Van Mossevelde, S; van der Zee, J; Sieben, A; Engelborghs, S; De Bleecker, J; Ivanoiu, A; Deryck, O; Edbauer, D; Zhang, M; Heeman, B; Bäumer, V; Van den Broeck, M; Mattheijssens, M; Peeters, K; Rogaeva, E; De Jonghe, P; Cras, P; Martin, J-J; de Deyn, P P; Cruts, M; Van Broeckhoven, C

    2016-08-01

    Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (Pdisease anticipation. Also, intermediate repeats (7-24 units) showed a slightly higher methylation degree (Pdisease mechanisms and have important implications for diagnostic counseling and potential therapeutic approaches.

  19. Mechanistic insights into aging, cell cycle progression, and stress response

    Directory of Open Access Journals (Sweden)

    Troy Anthony Alan Harkness

    2012-06-01

    Full Text Available The longevity of an organism depends on the health of its cells. Throughout life cells are exposed to numerous intrinsic and extrinsic stresses, such as free radicals, generated through mitochondrial electron transport, and ultraviolet irradiation. The cell has evolved numerous mechanisms to scavenge free radicals and repair damage induced by these insults. One mechanism employed by the yeast Saccharomyces cerevisiae to combat stress utilizes the Anaphase Promoting Complex (APC, an essential multi-subunit ubiquitin-protein ligase structurally and functionally conserved from yeast to humans that controls progression through mitosis and G1. We have observed that yeast cells expressing compromised APC subunits are sensitive to multiple stresses and have shorter replicative and chronological lifespans. In a pathway that runs parallel to that regulated by the APC, members of the Forkhead box (Fox transcription factor family also regulate stress responses. The yeast Fox orthologues Fkh1 and Fkh2 appear to drive the transcription of stress response factors and slow early G1 progression, while the APC seems to regulate chromatin structure, chromosome segregation, and resetting of the transcriptome in early G1. In contrast, under non-stress conditions, the Fkhs play a complex role in cell cycle progression, partially through activation of the APC. Direct and indirect interactions between the APC and the yeast Fkhs appear to be pivotal for lifespan determination. Here we explore the potential for these interactions to be evolutionarily conserved as a mechanism to balance cell cycle regulation with stress responses.

  20. Intense piano training on self-efficacy and physiological stress in aging.

    Science.gov (United States)

    Bugos, Jennifer A; Kochar, Simran; Maxfield, Nathan

    2016-07-01

    The aim of this study was to evaluate the effects of an intense piano training program on general self-efficacy, musical self-efficacy, and physiological stress in older adults. Self-efficacy refers to perceived beliefs regarding the performance of domain-specific tasks or activities, which contribute to psychological and physical health. A key challenge is to identify activities that promote self-efficacy in the aging population. Seventeen healthy community-dwelling older adults (60-85 years) with little to no previous musical training participated in a within subjects experimental design. Measures of self-efficacy and cortisol levels were administered over three time points: an initial pre-testing session, a second pre-testing following a two-week no treatment control period, and a post-testing session upon the completion of piano training. Intense piano training consisted of 30 hours of training (3 hours per day) in which high levels of achievement were required. Results of a three-way Repeated Measures ANOVA over all time points with pairwise comparisons revealed significantly (p < .05) enhanced musical self-efficacy post-training, F (2, 32) = 11.5, p < .001, d = .79. No significant changes in general self-efficacy or cortisol levels were found. These results suggest that domain-specific self-efficacy may increase as a result of short-term intense music training; however, short-term music training may not be sufficient to transfer to general self-efficacy.

  1. AGING EFFECTS OF REPEATEDLY GLOW-DISCHARGED POLYETHYLENE - INFLUENCE ON CONTACT-ANGLE, INFRARED-ABSORPTION, ELEMENTAL SURFACE-COMPOSITION, AND SURFACE-TOPOGRAPHY

    NARCIS (Netherlands)

    VANDERMEI, HC; STOKROOS, [No Value; SCHAKENRAAD, JM; BUSSCHER, HJ

    1991-01-01

    Aging effects of repeatedly oxygen glow-discharged polyethylene surfaces were determined by water contact angle measurements, infrared (IR) spectroscopy, X-ray photoelectron (XPS) spectroscopy, and surface topography determination. Glow-discharged surfaces were stored at room temperature and in liqu

  2. The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.

    Science.gov (United States)

    Andresen, J Michael; Gayán, Javier; Djoussé, Luc; Roberts, Simone; Brocklebank, Denise; Cherny, Stacey S; Cardon, Lon R; Gusella, James F; MacDonald, Marcy E; Myers, Richard H; Housman, David E; Wexler, Nancy S

    2007-05-01

    Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.

  3. The decay of Redox-stress Response Capacity is a substantive characteristic of aging: Revising the redox theory of aging.

    Science.gov (United States)

    Meng, Jiao; Lv, Zhenyu; Qiao, Xinhua; Li, Xiaopeng; Li, Yazi; Zhang, Yuying; Chen, Chang

    2017-04-01

    Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals. In response to paraquat stress, young individuals generated more ROS and activated signaling pathways including p-ERK, p-AKT and p-AMPKα/β. After the initial response, young individuals then promoted NRF2 translocation and induced additional antioxidant enzymes and higher expression of phase II enzymes, including SOD, CAT, GPX, HO-1, GSTP-1and others, to maintain redox homeostasis. Moreover, young individuals also demonstrated a better ability to degrade damaged proteins by up-regulating the expression of chaperones and improving proteasome activity. Based on these data, we propose a new concept "Redox-stress Response Capacity (RRC)", which suggests cells or organisms are capable of generating dynamic redox responses to activate cellular signaling and maintain cellular homeostasis. The decay of RRC is the substantive characteristic of aging, which gives a new understand of the redox theory of aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Neonatal stress affects the aging trajectory of female rats on the endocrine, temperature, and ventilatory responses to hypoxia.

    Science.gov (United States)

    Fournier, Sébastien; Gulemetova, Roumiana; Baldy, Cécile; Joseph, Vincent; Kinkead, Richard

    2015-04-01

    Human and animal studies on sleep-disordered breathing and respiratory regulation show that the effects of sex hormones are heterogeneous. Because neonatal stress results in sex-specific disruption of the respiratory control in adult rats, we postulate that it might affect respiratory control modulation induced by ovarian steroids in female rats. The hypoxic ventilatory response (HVR) of adult female rats exposed to neonatal maternal separation (NMS) is ∼30% smaller than controls (24), but consequences of NMS on respiratory control in aging female rats are unknown. To address this issue, whole body plethysmography was used to evaluate the impact of NMS on the HVR (12% O2, 20 min) of middle-aged (MA; ∼57 wk old) female rats. Pups subjected to NMS were placed in an incubator 3 h/day for 10 consecutive days (P3 to P12). Controls were undisturbed. To determine whether the effects were related to sexual hormone decline or aging per se, experiments were repeated on bilaterally ovariectomized (OVX) young (∼12 wk old) adult female rats. OVX and MA both reduced the HVR significantly in control rats but had little effect on the HVR of NMS females. OVX (but not aging) reduced the anapyrexic response in both control and NMS animals. These results show that hormonal decline decreases the HVR of control animals, while leaving that of NMS female animals unaffected. This suggests that neonatal stress alters the interaction between sex hormone regulation and the development of body temperature, hormonal, and ventilatory responses to hypoxia.

  5. The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

  6. The E-subgroup Pentatricopeptide Repeat Protein family in Arabidopsis thaliana and confirmation of the responsiveness PPR96 to abiotic stresses

    Directory of Open Access Journals (Sweden)

    Jia-Ming Liu

    2016-12-01

    Full Text Available Pentatricopeptide repeat (PPR proteins are extensive in all eukaryotes. Their functions remain as yet largely unknown. Mining potential stress responsive PPRs, and checking whether known PPR editing factors are affected in the stress treatments. It is beneficial to elucidate the regulation mechanism of PPRs involved in biotic and abiotic stress. Here, we explored the characteristics and origin of the 105 E subgroup PPRs in Arabidopsis thaliana. Phylogenetic analysis categorized the E subgroup PPRs into five discrete groups (Cluster I to V, and they may have a common origin in both A. thaliana and rice. An in silico expression analysis of the 105 E subgroup PPRs in A. thaliana was performed using available microarray data. 34 PPRs were differentially expressed during A. thaliana seed imbibition, seed development stage(s, and flowers development processes. To explore potential stress responsive PPRs, differential expression of 92 PPRs was observed in A. thaliana seedlings subjected to different abiotic stresses. qPCR data of E subgroup PPRs under stress conditions revealed that the expression of 5 PPRs was responsive to abiotic stresses. In addition, PPR96 is involved in plant responses to salt, abscisic acid (ABA, and oxidative stress. The T-DNA insertion mutation inactivating PPR96 expression results in plant insensitivity to salt, ABA, and oxidative stress. The PPR96 protein is localized in the mitochondria, and altered transcription levels of several stress-responsive genes under abiotic stress treatments. Our results suggest that PPR96 may important function in a role connecting the regulation of oxidative respiration and environmental responses in A. thaliana.

  7. Dietary grape poliphenols modulate oxidative stress in ageing rabbits

    Directory of Open Access Journals (Sweden)

    R. Della Loggia

    2010-01-01

    Full Text Available The imbalance between reactive oxygen species (ROS and antioxidant capacity of the organism leads to a condition of oxidative stress (Urso and Clarkson, 2003. Studies in humans and laboratory animals have reported that oxidative stress is related to some common degenerative diseases, such as cancer and cardiovascular pathologies (Pellegrini et al., 2003. Oxidative stress has also been identified as causative agent for diseases, such as decline of immune function and atherosclerosis (Meydani et al., 1998. In particular, reactive oxygen metabolites such as superoxide (O2-, hydrogen peroxide (H2O2 and hydroxyl radical (OH. have been reported to act as cytotoxic agents and damage unsaturated lipids in membranes (Girotti, 1998.

  8. Oxidative stress and CCN1 protein in human skin connective tissue aging

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    2016-06-01

    Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

  9. Post-Traumatic Stress Disorder among School Age Palestinian Children

    Science.gov (United States)

    Khamis, Vivian

    2005-01-01

    Objectives: This study was designed to assess the prevalence of PTSD among Palestinian school-age children. Variables that distinguish PTSD and non-PTSD children were examined, including child characteristics, socioeconomic status, family environment, and parental style of influence. Method: Participants were 1,000 children aged 12 to 16 years.…

  10. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

  11. Acute Stress Affects the Expression of Hippocampal Mu Oscillations in an Age-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Samir Takillah

    2017-09-01

    Full Text Available Anxiolytic drugs are widely used in the elderly, a population particularly sensitive to stress. Stress, aging and anxiolytics all affect low-frequency oscillations in the hippocampus and prefrontal cortex (PFC independently, but the interactions between these factors remain unclear. Here, we compared the effects of stress (elevated platform, EP and anxiolytics (diazepam, DZP on extracellular field potentials (EFP in the PFC, parietal cortex and hippocampus (dorsal and ventral parts of adult (8 months and aged (18 months Wistar rats. A potential source of confusion in the experimental studies in rodents comes from locomotion-related theta (6–12 Hz oscillations, which may overshadow the direct effects of anxiety on low-frequency and especially on the high-amplitude oscillations in the Mu range (7–12 Hz, related to arousal. Animals were restrained to avoid any confound and isolate the direct effects of stress from theta oscillations related to stress-induced locomotion. We identified transient, high-amplitude oscillations in the 7–12 Hz range (“Mu-bursts” in the PFC, parietal cortex and only in the dorsal part of hippocampus. At rest, aged rats displayed more Mu-bursts than adults. Stress acted differently on Mu-bursts depending on age: it increases vs. decreases burst, in adult and aged animals, respectively. In contrast DZP (1 mg/kg acted the same way in stressed adult and age animal: it decreased the occurrence of Mu-bursts, as well as their co-occurrence. This is consistent with DZP acting as a positive allosteric modulator of GABAA receptors, which globally potentiates inhibition and has anxiolytic effects. Overall, the effect of benzodiazepines on stressed animals was to restore Mu burst activity in adults but to strongly diminish them in aged rats. This work suggests Mu-bursts as a neural marker to study the impact of stress and DZP on age.

  12. Posture control development in children aged 2-7 years old, based on the changes of repeatability of the stability indices.

    Science.gov (United States)

    Sobera, Małgorzata; Siedlecka, Bożena; Syczewska, Małgorzata

    2011-03-10

    One of the most common problems encountered in posture control studies is relatively poor repeatability of postural stability measures based on the COP (center of pressure) time-series which results from the inherent variability of postural control. The repeatability of the data reflecting the postural control mechanisms in young children is still not well enough explained. The differences between of the repeatability of the stability indices of left and right foot may reflect the lateralization development of legs in the support function. The aim of the present study was two-fold: the assessment of the repeatability of the stability indices in three consecutive trials in young children, aged 2-7 years old, during quiet bipedal stance and the description of process of lower limbs lateralization, based on the difference of repeatability of both feet stability the indices changing with years. The subjects were 272 young healthy children aged 2-7 years old separated in 6 groups for children of different age. Each child stood for around 90s on two AccuSway force platforms (AMTI). The shifts of COP beneath left and right legs were recorded onto a computer by using appropriate software compatible with platforms. The indices of the ellipse area and velocity COP shifts were calculated. For assessment of the repeatability the concordance correlation coefficient (CCC) of the indices was used between the 1st and 2nd, 2nd and 3rd, and 1st and 3rd trials. Young children of 2-4 years old exhibit low level of the stability indices repeatability which increases in 5-year-old children, 6-year-olds revealed both low and high and 7-year-olds good and high levels of repeatability. Youngest children showed higher repeatability of the ellipse area of the left leg, 3- and 4-year-olds the right leg, while 6-year-olds again the left leg. In 5- and 7-year-olds there were no differences in the repeatability of stability indices between the left and right foot. The comparisons of the

  13. Prognostics Approach For Power Mosfet Under Thermal-Stress Aging

    Data.gov (United States)

    National Aeronautics and Space Administration — The prognostic technique for a power MOSFET presented in this paper is based on accelerated aging of MOSFET IRF520Npbf in a TO-220 package. The methodology utilizes...

  14. Repeatability of baseline corticosterone and short-term corticosterone stress responses, and their correlation with testosterone and body condition in a terrestrial breeding anuran (Platymantis vitiana).

    Science.gov (United States)

    Narayan, Edward J; Cockrem, John F; Hero, Jean-Marc

    2013-06-01

    Repeatability of physiological response variables, such as the stress hormone corticosterone, across numerous sampling occasions is an important assumption for their use as predictors of behaviour, reproduction and fitness in animals. Very few studies have actually tested this assumption in free-living animals under uncontrolled natural conditions. Non-invasive urine sampling and standard capture handling protocol have enabled the rapid quantification of baseline corticosterone and short-term corticosterone stress responses in anuran amphibians. In this study, established non-invasive methods were used to monitor physiological stress and urinary testosterone levels in male individuals of the terrestrial breeding Fijian ground frog (Platymantis vitiana). Adult male frogs (n = 20) were sampled at nighttime on three repeated occasions at intervals of 14 days during their annual breeding season on Viwa Island, Fiji. All frogs expressed urinary corticosterone metabolite responses to the capture and handling stressor, with some frogs showing consistently higher urinary corticosterone responses than others. Ranks of corticosterone values at 0, 4 and 8 h, and the corrected rank were highly significant (r = 0.75-0.99) between the three repeated sampling occasions. Statistical repeatabilities were high for baseline corticosterone (r = 0.973) and for corticosterone values at 2 h (r = 0.862), 4 h (r = 0.861), 6 h (r = 0.820) and 8 h (r = 0.926), and also for the total (inclusive of baseline corticosterone values) and the corrected integrated responses (index of the acute response) [r = 0.867 and r = 0.870]. Urinary testosterone levels also showed high statistical repeatability (r = 0.78). Furthermore, variation in baseline and short-term corticosterone stress responses was greater between individuals than within individuals. Baseline urinary corticosterone was significantly negatively correlated with the corrected integrated corticosterone response (r = -0.3, p breeding period

  15. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.; Snoek, L.B.; Bono, de M.; Kammenga, J.E.

    2013-01-01

    Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human d

  16. Reducing Listening-Related Stress in School-Aged Children with Autism Spectrum Disorder

    Science.gov (United States)

    Rance, Gary; Chisari, Donella; Saunders, Kerryn; Rault, Jean-Loup

    2017-01-01

    High levels of stress and anxiety are common in children with Autism Spectrum Disorder (ASD). Within this study of school-aged children (20 male, 6 female) we hypothesised that functional hearing deficits (also pervasive in ASD) could be ameliorated by auditory interventions and that, as a consequence, stress levels would be reduced. The use of…

  17. Effects of Swimming Training on Stress Levels of the Students Aged 11-13

    Science.gov (United States)

    Köroglu, Mihraç; Yigiter, Korkmaz

    2016-01-01

    The purpose of this research was to determine the effects of the swimming training program on stress levels of the students ages 11-13. To this end, 60 students from Private Sahin School in the Sakarya city participated in the study voluntarily. 60 students were divided into two groups and each group was included 30 students. Stress Level Scale II…

  18. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

    Science.gov (United States)

    Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not

  19. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats.

    Science.gov (United States)

    Azman, Khairunnuur Fairuz; Zakaria, Rahimah; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  20. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats

    Directory of Open Access Journals (Sweden)

    Khairunnuur Fairuz Azman

    2016-01-01

    Full Text Available Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A, 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  1. Chronic Stress Impairs Collateral Blood Flow Recovery in Aged Mice

    Science.gov (United States)

    2014-10-15

    0, normal; 1–5, cyanosis or loss of nail(s), where the score is dependent on the number of nails affected; 6–10, partial or complete atrophy of...digit(s), where the score reflects the number of digits affected; and 11, partial atrophy of forefoot [21]. Hind limb use scores (index of muscle function...brain, and cardiac fibrosis and, in many ways, provides a posttraumatic stress disorder (PTSD) model for mice [26]. As a model of physical/neurogenic

  2. Allopurinol Reduces Oxidative Stress in the Ovine Fetal Cardiovascular System After Repeated Episodes of Ischemia-Reperfusion

    NARCIS (Netherlands)

    Derks, Jan B.; Oudijk, Martijn A.; Torrance, Helen L.; Rademaker, Carin M. A.; Benders, Manon J.; Rosen, Karl G.; Cindrova-Davies, Tereza; Thakor, Avnesh S.; Visser, Gerard H. A.; Burton, Graham J.; van Bel, Frank; Giussani, Dino A.

    2010-01-01

    In complicated labor, neonatal outcome may depend not only on the extent of fetal asphyxia and acidosis but also on the effects on the fetal cardiovascular system of reactive oxygen species (ROS) generated during the ischemia-reperfusion (I/R) associated with repeated compressions of the umbilical c

  3. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    Science.gov (United States)

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan; Shirzad, Hedayatolah

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.

  4. The ecological stress theory of aging and hormesis: an energetic evolutionary model.

    Science.gov (United States)

    Parsons, Peter A

    2007-06-01

    Free-living organisms normally struggle to exist in harsh environments that are nutritionally and energetically inadequate, where evolutionary adaptation is challenged by internal stresses within organisms and external stresses from the environment. The incorporation of environmental variables into aging theories such as the free-radical and metabolic rate/oxidative stress theories, is the basis of the ecological stress theory of aging and hormesis. Environmental variation from optimum to lethal extremes gives a fitness-stress continuum, where energetic efficiency, or fitness, is inversely related to stress level; in the evolutionary context survival is a more direct measure of fitness for assessing aging than is lifespan. On this continuum, the hormetic zone is in the optimum region, while aging emphasizes survival towards lethal extremes. At the limits of survival, a convergence of physiological and genetical processes is expected under accumulating stress from Reactive Oxygen Species, ROS. Limited ecologically-oriented studies imply that major genes are important towards limits of survival compared with the hormetic zone. Future investigations could usefully explore outlier populations physiologically and genetically, since there is the likelihood that genetic variability may be lower in those cohorts managing to survive to extremely advanced ages as found in highly stressed ecological outlier populations. If so, an evolutionary explanation of the mortality-rate decline typical of cohorts of the extremely old emerges. In summary, an energetic evolutionary approach produces a general aging theory which automatically incorporates hormesis, since the theory is based on a fitness-stress continuum covering the whole range of possible abiotic environments of natural populations.

  5. Pregnancy-specific stress, preterm birth, and gestational age among high-risk young women.

    Science.gov (United States)

    Cole-Lewis, Heather J; Kershaw, Trace S; Earnshaw, Valerie A; Yonkers, Kimberly Ann; Lin, Haiqun; Ickovics, Jeannette R

    2014-09-01

    There is evidence that pregnancy-specific stress is associated with preterm birth. The purpose of this study is to examine the association between change in pregnancy-specific stress over the course of pregnancy and birth outcomes (i.e., preterm birth and gestational age) in an understudied but vulnerable group using a theoretically derived model. Multivariate linear and logistic regression techniques were used to examine the association between pregnancy-specific stress (measured in second and third trimester) and length of gestation (i.e., preterm birth and gestational age) among a sample of 920 Black and/or Latina adolescent and young women. Second trimester pregnancy-specific stress was not associated with preterm birth or gestational age. Third trimester pregnancy-specific stress was associated with preterm birth but not with gestational age. Change in pregnancy-specific stress between second and third trimester was significantly associated with increased likelihood of preterm delivery and shortened gestational age, even after controlling for important biological, behavioral, psychological, interpersonal, and sociocultural risk factors. Findings emphasize the importance of measuring pregnancy-specific stress across pregnancy, as the longitudinal change from second to third trimester was significantly associated with length of gestation measured both as a dichotomous variable (preterm birth) and a continuous variable (gestational age). Furthermore, this is the first study to observe the association of pregnancy-specific stress with length of gestation in this understudied population-unique in age, race, and ethnicity. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  6. Post-traumatic stress and age variation in amygdala volumes among youth exposed to trauma.

    Science.gov (United States)

    Weems, Carl F; Klabunde, Megan; Russell, Justin D; Reiss, Allan L; Carrión, Victor G

    2015-12-01

    Theoretically, normal developmental variation in amygdala volumes may be altered under conditions of severe stress. The purpose of this article was to examine whether posttraumatic stress moderates the association between age and amygdala volumes in youth exposed to traumatic events who are experiencing symptoms of post-traumatic stress disorder (PTSD). Volumetric imaging was conducted on two groups of youth aged 9-17 years: 28 with exposure to trauma and PTSD symptoms (boys = 15, girls = 13) and 26 matched (age, IQ) comparison youth (Controls; boys = 12, girls = 14). There was a significant group by age interaction in predicting right amygdala volumes. A positive association between age and right amygdala volumes was observed, but only in PTSD youth. These associations with age remained when controlling for IQ, total brain volumes and sex. Moreover, older youth with PTSD symptoms had relatively larger right amygdala volumes than controls. Findings provide evidence that severe stress may influence age-related variation in amygdala volumes. Results further highlight the importance of utilizing age as an interactive variable in pediatric neuroimaging research, in so far as age may act as an important moderator of group differences.

  7. LIFE EVENTS WITH STRESSFUL EFFECT ON PATIENTS WITH SCHIZOPHRENIA ACCORDING TO THE SEX AND AGE.

    Directory of Open Access Journals (Sweden)

    Lilia Nikolova

    2012-08-01

    Full Text Available According to the literature life events with stressful effect are significant both for initiation and progress of the schizophrenia. Having this in mind we set our aim to be investigating the relationship between life events (considered as stressful, sex and age trough questioning 50 patients with paranoid schizophrenia. The results of our study showed presence of correlation between some of the studied life events, assessed as stressful. The analysis of the data revealed that both sex and age are influencing the assessment of the significance of the life events and “increases” their importance both for women and men.

  8. The Effect of Age and Initial Central Retinal Thickness on Earlier Need of Repeat Ozurdex Treatment for Macular Edema Due to Retinal Vein Occlusion: A Retrospective Case Series.

    Science.gov (United States)

    Lin, Chun-Ju; Chen, Huan-Sheng; Su, Cheng-Wen; Tien, Peng-Tai; Lin, Jane-Ming; Chen, Wen-Lu; Kuo, Chung-Yuan; Lai, Chun-Ting; Tsai, Yi-Yu

    2017-09-26

    To evaluate the effects of dexamethasone intravitreal implant (Ozurdex) and identify risk factors for repeated treatment in patients with macula edema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Patients followed up for at least 6 months were enrolled from 2013 to 2016. Dexamethasone intravitreal implant was given as the baseline treatment. For evaluation of dexamethasone intravitreal implant effects and complications, the demographics, medical history, best-corrected visual acuity (BCVA), intraocular pressure, and central retinal thickness (CRT) were recorded. Multivariate Cox proportional hazard model and logistic regression were used to identify factors for repeated treatment. Twenty-three BRVO and 11 CRVO patients were enrolled. There were 15 males and 19 females. Fifteen (44.12%) patients needed only one dexamethasone intravitreal implant. The peak CRT and BCVA significantly improved. Comparing single-injection with multiple-injection group, age and initial CRT more than 400 μm were significantly higher in the multiple-injection group. From multivariate logistic regression and Cox proportional hazards analysis, patients with age older than 55 years and initial CRT more than 400 μm had higher risk for multiple injections. Patients receiving as-needed schedule of dexamethasone intravitreal implant had significant peak CRT and BCVA improvement. Age older than 55 years and initial CRT more than 400 μm were significant risk factors associated with repeated dexamethasone intravitreal implant treatment.

  9. Analysis of Deformation in Inconel 718 When the Stress Anomaly and Dynamic Strain Aging Coexist

    Science.gov (United States)

    Follansbee, Paul S.

    2016-09-01

    Deformation in Inconel 718 in the presence of combined effects of the stress anomaly and dynamic strain aging is analyzed according to an internal state variable model formulation. The analysis relies on the availability of experimental data in regimes of behavior where both the stress anomaly and dynamic strain aging are absent. A model that introduces two internal state variables—one characterizing interactions of dislocations with solute atoms and one characterizing interaction of dislocations with precipitates—is shown to adequately describe the temperature and strain-rate dependence of the yield stress in several superalloy systems. Strain hardening is then added with a third internal state variable to enable description of the full stress-strain curve. These equations are extrapolated into regimes where the stress anomaly and dynamic strain aging are present to identify signatures of their effects and to compare to similar analyses in a variety of metal systems. Dynamic strain aging in Inconel 718 follows similar trends to those observed previously. The magnitude of the stress anomaly tracks measurements of stress vs test temperature in pure Ni3Al. Several trends in the strain-rate sensitivity of elevated temperature deformation in superalloys are identified based on limited availability of measurements over a wide range of strain rates or tests using strain-rate changes.

  10. Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin-induced murine model of asthma.

    Science.gov (United States)

    Li, Bei; Duan, Xiaohong; Xu, Changqing; Wu, Jinfeng; Liu, Baojun; Du, Yiji; Luo, Qingli; Jin, Hualiang; Gong, Weiyi; Dong, Jingcheng

    2014-04-01

    Evidence shows that psychosocial stress exacerbates asthma, but there is little intervention to alleviate negative effects of psychosocial stress on asthma. We investigated the role of icariin in anti-inflammation and anti-anxiety potential in a murine model combined psychosocial stress with allergic exposure. The results indicated that icariin administered remarkable increased activity in the center of the open field, reversed airway hyperresponsivenesss, reduced inflammatory cytokine infiltration to the lung and whole body and also in part recovered glucocorticoid responsiveness. Furthermore, our data also showed that icariin significantly inhibited increases of corticosterone and markedly increased glucocorticoid receptor mRNA and protein expression in the lungs of mice exposed to both stress and allergen. Collectively, we speculate that inducing glucocorticoid receptor modulation might be the potential mechanisms of icariin to facilitate corticosteroid responsiveness of cytokine production.

  11. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes.

    Science.gov (United States)

    Collins, John A; Wood, Scott T; Nelson, Kimberly J; Rowe, Meredith A; Carlson, Cathy S; Chubinskaya, Susan; Poole, Leslie B; Furdui, Cristina M; Loeser, Richard F

    2016-03-25

    Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1-3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observedin situin human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism.

  12. Murine Model of Repeated Exposures to Conspecific Trained Aggressors Simulates Features of Post-Traumatic Stress Disorder

    Science.gov (United States)

    2012-07-20

    Rasmusson and Charney [95], Stam et al. [96], and Siegmund and Wotjak [6]. In our studies, the persis- tence of some acutely altered behaviors after...served in Iraq and Afghanistan: possible explanations. Journal of Traumatic Stress 2010;23:59–68. [6] Siegmund A, Wotjak CT. Toward an animal model...Posttraumatic Stress Disorder (PTSD). Behavioural Brain Research 2009;205:544–9. ral BrR. Hammamieh et al. / Behaviou [11] Siegmund A, Dahlhoff M, Habersetzer

  13. Effects of Culture, Age, Gender, and Repeated Trials on Rote Song Learning Skills of Children 6-9 Years Old from England, Panama, Poland, Spain, and the United States.

    Science.gov (United States)

    Moore, Randall S.; Brotons, Melissa; Fyk, Janina; Castillo, Argelis

    1997-01-01

    Examines the effect of repeated trials on children aged six to nine from different countries learning a new song. States that: (1) culture influences responses; (2) rote singing improves with age; (3) girls responses are better; and (4) children repeat rhythms more accurately before they can pitch match melodic contours and precise pitches. (CMK)

  14. Predictors of Care-Giver Stress in Families of Preschool-Aged Children with Developmental Disabilities

    Science.gov (United States)

    Plant, K. M.; Sanders, M. R.

    2007-01-01

    Background: This study examined the predictors, mediators and moderators of parent stress in families of preschool-aged children with developmental disability. Method: One hundred and five mothers of preschool-aged children with developmental disability completed assessment measures addressing the key variables. Results: Analyses demonstrated that…

  15. mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases.

    Science.gov (United States)

    Yang, Z; Ming, X-F

    2012-12-01

    The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic diseases accelerate aging process. Studies in experimental animal models demonstrate similarity of metabolic and cardiovascular phenotypes in metabolic diseases and old age, e.g. insulin resistance, oxidative stress, chronic low grade inflammation, cardiac hypertrophy, cardiac fibrosis, and heart failure, as well as vascular dysfunctions. Despite intensive research, the molecular mechanisms linking metabolic stress, aging, and ultimately cardiovascular diseases are still elusive. Although the mammalian target of rapamycin (mTOR) signalling is a well known regulator of metabolism and lifespan in model organisms, its central role in linking metabolic stress, aging and cardiovascular diseases is recently emerging. In this article, we review the evidence supporting the role of mTOR signalling as a molecular interface connecting metabolic stress, aging and cardiovascular diseases. The therapeutic potentials of targeting mTOR signalling to protect against metabolic and age-associated cardiovascular diseases are discussed. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

  16. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Hasselholt, Stine; Miyashita, Namiyo

    2012-01-01

      Increased oxidative stress in the brain has consistently been implied in ageing and in several degenerative brain disorders. Acting as a pivotal antioxidant in the brain, vitamin C is preferentially retained during deficiency and may play an essential role in neuroprotection during ageing. Thus...

  17. EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  18. [The role of oxidative stress in skin aging].

    Science.gov (United States)

    Kozina, L S; Borzova, I V; Arutiunov, V A; Ryzhak, G A

    2012-01-01

    The review covers the literature proving that ROS formation in aging overbalances the antioxidant defense system potential of the skin structure (horny layer, epidermis and dermis). It has been shown that ROS are involved in the pathogenesis of inflammatory processes and allergic responses in the skin. The role of ROS and antioxidant systems in the cell-mediated responses associated with the MAP kinase activity in the skin is discussed. Special attention is paid to the ultraviolet irradiation exposure, which accounts for its genotoxic, immunosuppressive and carcinogenic effects on the skin.

  19. Aging, stressing and solderability of electroplated and electroless copper

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, N.R.; Hosking, F.M.

    1995-08-01

    Organic inhibitors can be used to prevent corrosion of metals have application in the electronics industry as solderability preservatives. We have developed a model to describe the action of two inhibitors (benzotriazole and imidazole) during the environmental aging and soldering process. The inhibitors bond with the metal surface and form a barrier that prevents or retards oxidation. At soldering temperatures, the metal-organic complex breaks down leaving an oxide-free metal surface that allows excellent wetting by the molten solder. The presence of the inhibitor retards the wetting rate relative to clean copper but provides a vast improvement relative to oxidized copper.

  20. Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration.

    Science.gov (United States)

    Libby, Richard T; Gould, Douglas B

    2010-01-01

    Age-related macular degeneration (AMD) is a multi-factorial disease and a leading cause of blindness. Proteomic and genetic data suggest that activation or de-repression of the alternate complement cascade of innate immunity is involved in end-stage disease. Several lines of evidence suggest that production of reactive oxygen species and chronic oxidative stress lead to protein and lipid modifications that initiate the complement cascade. Understanding the triggers of these pathogenic pathways and the site of the primary insult will be important for development of targeted therapeutics. Endoplasmic reticulum (ER) stress from misfolded mutant proteins and other sources are an important potential tributary mechanism. We propose that misfolded-protein-induced ER stress in the retinal-pigmented epithelium and/or choroid could lead to chronic oxidative stress, complement deregulation and AMD. Small molecules targeted to ER stress and oxidative stress could allow for a shift from disease treatment to disease prevention.

  1. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    Science.gov (United States)

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-01

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  2. Aging induces cardiac diastolic dysfunction, oxidative stress, accumulation of advanced glycation endproducts and protein modification.

    Science.gov (United States)

    Li, Shi-Yan; Du, Min; Dolence, E Kurt; Fang, Cindy X; Mayer, Gabriele E; Ceylan-Isik, Asli F; LaCour, Karissa H; Yang, Xiaoping; Wilbert, Christopher J; Sreejayan, Nair; Ren, Jun

    2005-04-01

    Evidence suggests that aging, per se, is a major risk factor for cardiac dysfunction. Oxidative modification of cardiac proteins by non-enzymatic glycation, i.e. advanced glycation endproducts (AGEs), has been implicated as a causal factor in the aging process. This study was designed to examine the role of aging on cardiomyocyte contractile function, cardiac protein oxidation and oxidative modification. Mechanical properties were evaluated in ventricular myocytes from young (2-month) and aged (24-26-month) mice using a MyoCam system. The mechanical indices evaluated were peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt). Oxidative stress and protein damage were evaluated by glutathione and glutathione disulfide (GSH/GSSG) ratio and protein carbonyl content, respectively. Activation of NAD(P)H oxidase was determined by immunoblotting. Aged myocytes displayed a larger cell cross-sectional area, prolonged TR90, and normal PS, +/- dL/dt and TPS compared with young myocytes. Aged myocytes were less tolerant of high stimulus frequency (from 0.1 to 5 Hz) compared with young myocytes. Oxidative stress and protein oxidative damage were both elevated in the aging group associated with significantly enhanced p47phox but not gp91phox expression. In addition, level of cardiac AGEs was approximately 2.5-fold higher in aged hearts than young ones determined by AGEs-ELISA. A group of proteins with a molecular range between 50 and 75 kDa with pI of 4-7 was distinctively modified in aged heart using one- or two-dimension SDS gel electrophoresis analysis. These data demonstrate cardiac diastolic dysfunction and reduced stress tolerance in aged cardiac myocytes, which may be associated with enhanced cardiac oxidative damage, level of AGEs and protein modification by AGEs.

  3. Age-related Decline of Abiotic Stress Tolerance in Young Drosophila melanogaster Adults.

    Science.gov (United States)

    Colinet, Hervé; Chertemps, Thomas; Boulogne, Isabelle; Siaussat, David

    2016-12-01

    Stress tolerance generally declines with age as a result of functional senescence. Age-dependent alteration of stress tolerance can also occur in early adult life. In Drosophila melanogaster, evidence of such a decline in young adults has only been reported for thermotolerance. It is not known whether early adult life entails a general stress tolerance reduction and whether the response is peculiar to thermal traits. The present work was designed to investigate whether newly eclosed D melanogaster adults present a high tolerance to a range of biotic and abiotic insults. We found that tolerance to most of the abiotic stressors tested (desiccation, paraquat, hydrogen peroxide, deltamethrin, and malathion) was high in newly eclosed adults before dramatically declining over the next days of adult life. No clear age-related pattern was found for resistance to biotic stress (septic or fungal infection) and starvation. These results suggest that newly eclosed adults present a culminating level of tolerance to extrinsic stress which is likely unrelated to immune process. We argue that stress tolerance variation at very young age is likely a residual attribute from the previous life stage (ontogenetic carryover) or a feature related to the posteclosion development. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin

    Directory of Open Access Journals (Sweden)

    Khimara Naidoo

    2017-01-01

    Full Text Available Skin ageing is a complex process that is determined by both intrinsic and extrinsic factors, which leads to a progressive loss of structure and function. There is extensive evidence indicating that oxidative stress induced by reactive oxygen species plays an important role in the process of human skin ageing. Mitochondria are the major source of cellular oxidative stress and are widely implicated in cutaneous ageing. Extrinsic skin ageing is driven to a large extent by environmental factors and external stressors such as ultraviolet radiation (UVR, pollution and lifestyle factors which have been shown to stimulate the production of reactive oxygen species and generate oxidative stress. The oxidative damage from these exogenous sources can impair skin structure and function, leading to the phenotypic features of extrinsic skin ageing. The following review highlights the current evidence surrounding the role of mitochondria and oxidative stress in the ageing process and the influence of environmental factors such as ultraviolet radiation, pollution and diet on skin ageing.

  5. Happily (never after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

    Directory of Open Access Journals (Sweden)

    Annika Höhn

    2017-04-01

    Full Text Available Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.

  6. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    Science.gov (United States)

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  7. The phenome analysis of mutant alleles in Leucine-Rich Repeat Receptor-Like Kinase genes in rice reveals new potential targets for stress tolerant cereals.

    Science.gov (United States)

    Dievart, Anne; Perin, Christophe; Hirsch, Judith; Bettembourg, Mathilde; Lanau, Nadège; Artus, Florence; Bureau, Charlotte; Noel, Nicolas; Droc, Gaétan; Peyramard, Matthieu; Pereira, Serge; Courtois, Brigitte; Morel, Jean-Benoit; Guiderdoni, Emmanuel

    2016-01-01

    Plants are constantly exposed to a variety of biotic and abiotic stresses that reduce their fitness and performance. At the molecular level, the perception of extracellular stimuli and the subsequent activation of defense responses require a complex interplay of signaling cascades, in which protein phosphorylation plays a central role. Several studies have shown that some members of the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) family are involved in stress and developmental pathways. We report here a systematic analysis of the role of the members of this gene family by mutant phenotyping in the monocotyledon model plant rice, Oryza sativa. We have then targeted 176 of the ∼320 LRR-RLK genes (55.7%) and genotyped 288 mutant lines. Position of the insertion was confirmed in 128 lines corresponding to 100 LRR-RLK genes (31.6% of the entire family). All mutant lines harboring homozygous insertions have been screened for phenotypes under normal conditions and under various abiotic stresses. Mutant plants have been observed at several stages of growth, from seedlings in Petri dishes to flowering and grain filling under greenhouse conditions. Our results show that 37 of the LRR-RLK rice genes are potential targets for improvement especially in the generation of abiotic stress tolerant cereals.

  8. Residual stress analysis in aged graphite/PMR-15 composites using X-ray diffraction

    Energy Technology Data Exchange (ETDEWEB)

    Benedikt, B. [Los Alamos National Laboratory, Engineering Sciences and Applications Division, Los Alamos, NM 87545 (United States)]. E-mail: bbenedikt@lanl.gov; Lewis, M. [Los Alamos National Laboratory, Engineering Sciences and Applications Division, Los Alamos, NM 87545 (United States); Rangaswamy, P. [Los Alamos National Laboratory, Engineering Sciences and Applications Division, Los Alamos, NM 87545 (United States); Kumosa, M. [Center for Advanced Materials and Structures, Department of Engineering, University of Denver, 2390 South York St., Denver, CO 80208 (United States); Predecki, P. [Center for Advanced Materials and Structures, Department of Engineering, University of Denver, 2390 South York St., Denver, CO 80208 (United States); Kumosa, L. [Center for Advanced Materials and Structures, Department of Engineering, University of Denver, 2390 South York St., Denver, CO 80208 (United States); Gentz, M. [Center for Advanced Materials and Structures, Department of Engineering, University of Denver, 2390 South York St., Denver, CO 80208 (United States)

    2006-04-15

    In this paper, we present and discuss the methodology to monitor average residual stresses in aged high temperature unidirectional and woven graphite fiber/PMR-15 composites. The aging experiments were performed at 315 deg. C for 1170 h in nitrogen and 1064 h in air, respectively. The proposed methodology was based on X-ray diffraction (XRD) strain measurements in embedded crystalline metallic inclusions. The aging experiments performed in nitrogen showed an increasing trend in the measured residual stresses from the embedded inclusions with aging time. In contrast, the aging experiments performed in air showed an increasing trend up to {approx}200 h and then dropped by {approx}40% for both unidirectional and woven composites. To extract the average stresses in the composite matrix from the average stresses in embedded inclusions as determined using XRD, the well-established Eshelby/Mori-Tanaka method was used. In addition, to address the effect of inclusion interactions, we also computed the average stresses in the embedded inclusions by taking into account inclusion interactions within the frame-work of the Eshelby/Mori-Tanaka method. It was shown that the interactions between the inclusions did not significantly disturb the average stresses in the inclusions, thereby validating the Eshelby/Mori-Tanaka method used in our analysis. Finally, we show that for an aging process that does not cause any damage to a composite matrix, a relatively simple computation based on the visco-elastic Eshelby/Mori-Tanaka method is sufficient to determine the average stress field in a composite matrix as compared with the predictions based on classical lamination plate theory (CLPT). However, if significant matrix degradation occurs, the current micromechanical modeling approach would likely produce erroneous results.

  9. Algorithm-Based Fetal Gender Determination Using X and Y Mini-Short Tandem Repeats at Early Gestational Ages

    Directory of Open Access Journals (Sweden)

    Aghanoori

    2016-02-01

    Full Text Available Background Detection of fetal DNA in maternal blood has been examined by many research groups for a few years; thereby, scientists have a shorter way to take to approach prenatal diagnosis of abnormal pregnancies. The Y chromosome sequences have recently become the most common applicable indices for fetal sex determination. Objectives We conducted an algorithmic X and Y mini-Short Tandem Repeats (STRs genotyping method that could solve the problem of false negative (no detection of Y sequences results of previous methods. Patients and Methods Blood samples were obtained from 106 pregnant women and their spouses. Conventional PCR amplified 19 mini-Short Tandem Repeats (STRs and three non-STR markers, which were subsequently genotyped by the means of Polyacrylamide gel electrophoresis (PAGE. Results Sensitivity and specificity of the mini-STR genotyping method for fetal DNA detection were calculated (95.9% and 98%, respectively with a confidence interval of 95%. In addition, sensitivity and informativeness were computed for each of the single mini-STR markers in our conventional PCR method. We also introduced the minimum number of mini-STRs needed to reach maximum validity for fetal gender determination in clinical settings. Conclusions Algorithm-based mini-STR genotyping method significantly increases the reliability (sensitivity and specificity of gender determination using free fetal DNA and could be applied in prenatal clinical testing.

  10. Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age.

    Science.gov (United States)

    Liu, Jianhui; Zhao, Yanhong; Yang, Junjun; Zhang, Xiaoqing; Zhang, Wei; Wang, Peijun

    2017-02-01

    Inhalation anesthetics facilitate surgical procedures in millions of children each year. However, animal studies demonstrate that exposure to the inhalation anesthetic isoflurane may cause neuronal cell death in developing brains. The long-term cytotoxic effects of sevoflurane, the most popular pediatric anesthetic, have not been compared with isoflurane. Thus, this study was designed to compare the effects of equipotent doses of these two anesthetics on neonatal long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized mice served as controls. The effects of anesthesia on learning and memory were assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60 respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were determined by Western Blot. Neuron structure and apoptosis were assessed via Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused different degrees of apoptosis and damaged hippocampal neurons in neonatal mice, particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our findings suggest that isoflurane induces significantly greater neurodegeneration than an equipotent minimum alveolar concentration of sevoflurane.

  11. Effects of perch access and age on physiological measures of stress in caged White Leghorn pullets.

    Science.gov (United States)

    Yan, F F; Hester, P Y; Enneking, S A; Cheng, H W

    2013-11-01

    The neuroendocrine system controls animals' adaptability to their environments by releasing psychotropic compounds such as catecholamines [epinephrine (EP), norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5-hydroxytryptamine or 5-HT). Changes of these neuroendocrine compounds have been used as biomarkers of animals' stress responses associated with their well-being. Assuming that pullets, like laying hens, are highly motivated to perch, we hypothesize that pullets with access to perches will experience less stress than pullets that never have access to perches. The objective of this study was to examine the effects of perch access and age on physiological measurements of stress in White Leghorn pullets housed in conventional cages. Hatchlings (n = 1,064) were randomly assigned to 28 cages. Two parallel metal round perches were installed in each of 14 cages assigned the perch treatment, whereas control cages were without perches. Two birds per cage were bled at wk 4, 6, and 12 wk of age. Plasma levels of CORT, DA, EP, and NE, blood concentrations of 5-HT and Trp, and heterophil to lymphocyte ratios were measured. Data were analyzed using a 2-way ANOVA. The perch treatment or its interaction with age did not affect any parameter measured in the study. The increase in the concentrations of circulating EP, NE, 5-HT (numerical increase at 4 wk), and Trp in 4- and 6-wk-old pullets compared with 12-wk-old pullets is unclear, but may have been due to acute handling stress at younger ages. In contrast, concentrations of DA were less at 4 wk compared with levels at 6 and 12 wk of age. Plasma CORT levels and the heterophil to lymphocyte ratio, indicators of long-term stress, were unaffected by age (P = 0.07 and 0.49, respectively). These results indicated that age, but not perch access, affects neuroendocrine homeostasis in White Leghorn pullets. Pullets that were never exposed to perches showed no evidence of eliciting a stress response.

  12. Physiological responding to stress in middle-aged males enriched for longevity

    DEFF Research Database (Denmark)

    Jansen, Steffy W M; van Heemst, Diana; van der Grond, Jeroen

    2016-01-01

    Individuals enriched for familial longevity display a lower prevalence of age-related diseases, such as cardiovascular- and metabolic diseases. Since these diseases are associated with stress and increased cortisol levels, one of the underlying mechanisms that may contribute to healthy longevity...... might be a more adaptive response to stress. To investigate this, male middle-aged offspring from long-lived families (n = 31) and male non-offspring (with no familial history of longevity) (n = 26) were randomly allocated to the Trier Social Stress Test or a control condition in an experimental design....... Physiological (cortisol, blood pressure, heart rate) and subjective responses were measured during the entire procedure. The results showed that Offspring had lower overall cortisol levels compared to Non-offspring regardless of condition, and lower absolute cortisol output (AUCg) during stress compared to Non...

  13. Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

    Directory of Open Access Journals (Sweden)

    Maria W. Mauritz

    2016-09-01

    Full Text Available Background: In the Netherlands, most patients with severe mental illness (SMI receive flexible assertive community treatment (FACT provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1 PTSD and dissociative symptoms changes and (2 changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25 with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results

  14. Narrative exposure therapy for posttraumatic stress disorder associated with repeated interpersonal trauma in patients with severe mental illness: a mixed methods design

    Science.gov (United States)

    Mauritz, Maria W.; Van Gaal, Betsie G. I.; Jongedijk, Ruud A.; Schoonhoven, Lisette; Nijhuis-van der Sanden, Maria W. G.; Goossens, Peter J. J.

    2016-01-01

    Background In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the

  15. Effects of psychological stress on hypertension in middle-aged Chinese: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bo Hu

    Full Text Available We examined the effect and relative contributions of different types of stress on the risk of hypertension. Using cluster sampling, 5,976 community-dwelling individuals aged 40-60 were selected. Hypertension was defined according to the Seventh Report of the Joint National Committee, and general psychological stress was defined as experiencing stress at work or home. Information on known risk factors of hypertension (e.g., physical activity levels, food intake, smoking behavior was collected from participants. Logistic regression analysis was used to determine the associations between psychological stress and hypertension, calculating population-attributable risks and 95% confidence intervals (CIs. General stress was significantly related to hypertension (odds ratio [OR] = 1.247, 95% CI [1.076, 1.446]. Additionally, after adjustment for all other risk factors, women showed a greater risk of hypertension if they had either stress at work or at home: OR = 1.285, 95% CI (1.027, 1.609 and OR = 1.231, 95% CI (1.001, 1.514, respectively. However, this increased risk for hypertension by stress was not found in men. General stress contributed approximately 9.1% (95% CI [3.1, 15.0] to the risk for hypertension. Thus, psychological stress was associated with an increased risk for hypertension, although this increased risk was not consistent across gender.

  16. Acute stress affects free recall and recognition of pictures differently depending on age and sex.

    Science.gov (United States)

    Hidalgo, Vanesa; Pulopulos, Matias M; Puig-Perez, Sara; Espin, Laura; Gomez-Amor, Jesus; Salvador, Alicia

    2015-10-01

    Little is known about age differences in the effects of stress on memory retrieval. Our aim was to perform an in-depth examination of acute psychosocial stress effects on memory retrieval, depending on age and sex. For this purpose, data from 52 older subjects (27 men and 25 women) were reanalyzed along with data from a novel group of 50 young subjects (26 men and 24 women). Participants were exposed to an acute psychosocial stress task (Trier Social Stress Test) or a control task. After the experimental manipulation, the retrieval of positive, negative and neutral pictures learned the previous day was tested. As expected, there was a significant response to the exposure to the stress task, but the older participants had a lower cortisol response to TSST than the younger ones. Stress impaired free recall of emotional (positive and negative) and neutral pictures only in the group of young men. Also in this group, correlation analyses showed a marginally significant association between cortisol and free recall. However, exploratory analyses revealed only a negative relationship between the stress-induced cortisol response and free recall of negative pictures. Moreover, stress impaired recognition memory of positive pictures in all participants, although this effect was not related to the cortisol or alpha-amylase response. These results indicate that both age and sex are critical factors in acute stress effects on specific aspects of long-term memory retrieval of emotional and neutral material. They also point out that more research is needed to better understand their specific role.

  17. Healthy aging does not compromise the augmentation of cardiac function during heat stress.

    Science.gov (United States)

    Gagnon, Daniel; Romero, Steven A; Ngo, Hai; Sarma, Satyam; Cornwell, William K; Poh, Paula Y S; Stoller, Douglas; Levine, Benjamin D; Crandall, Craig G

    2016-10-01

    During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures. Copyright © 2016 the American Physiological Society.

  18. Stabilizing internal stress as the thermodynamic factor of martensite aging effects

    Energy Technology Data Exchange (ETDEWEB)

    Kosogor, Anna [Department of Radiophysics, Taras Shevchenko University, 03022 Kyiv (Ukraine); L' vov, Victor A., E-mail: victorlvov@univ.kiev.ua [Department of Radiophysics, Taras Shevchenko University, 03022 Kyiv (Ukraine); Institute of Magnetism, Vernadsky Str. 36-b, 03142 Kyiv (Ukraine); Soederberg, Outi; Hannula, Simo-Pekka [Department of Materials Science and Engineering, Aalto University School of Chemical Technology, PO Box 16200, Espoo FI-00076 Aalto (Finland)

    2011-05-15

    Highlights: > A martensite aging is accompanied by reconfiguration of the crystal defects system. > The reconfiguration causes an internal stressing of crystal lattice. > The internal stressing elevates the martensitic transformation temperature. > A theory that accounts for the internal stress adequately describes aging effects. > A quantitative description of aging effects observed in Au-Cd alloys is presented. - Abstract: The symmetry-conforming Landau theory has been developed for the description of interplay between the symmetry of the deformable crystal lattice and the configuration of crystallographic defects in martensitic alloys. For this purpose, the multi-component non-scalar order parameter describing the slow reconfiguration of defects after the deformation of crystal lattice has been introduced within the framework of the Landau theory of martensitic transformations (MTs). Due to the transformational equivalence of the configurational order parameter and strain/stress tensor components, the conception of stabilizing internal stress (SIS), which is linearly related to this parameter, has been formulated. The complete agreement between the developed theory and the symmetry-conforming short-range-order principle formulated by Ren and Otsuka has been established. The effect of stabilizing the product (martensitic) phase after aging has been described by considering the stress-temperature phase diagram, which was constructed by taking into account the time dependence of SIS. The applicability of the theory to the aging effects in the Au-Cd shape memory alloy has been demonstrated. The time dependencies of the experimentally observed slow changes in the MT temperatures, lattice parameters and yield stress values have been derived from the SIS conception.

  19. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    Directory of Open Access Journals (Sweden)

    Mohamed Saber Numan

    2015-02-01

    Full Text Available Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur.

  20. The sources and manifestations of stress amongst school-aged dyslexics, compared with sibling controls.

    Science.gov (United States)

    Alexander-Passe, Neil

    2008-11-01

    All school children experience stress at some point in their school careers. This study investigates whether dyslexic children, by way of their educational and social difficulties, experience higher levels of stress at school. The School Situation Survey was used to investigate both the sources and manifestations of stress amongst dyslexic children and non-dyslexic sibling controls. Samples were broken down by gender, age and the size of families. Results suggest significant differences between the groups, with dyslexics in academic years 3-5 experiencing the highest stress levels, specifically in interactions with teachers, worries over academic examinations (SATs) and performance testing, causing emotional (fear, shyness and loneliness) and physiological (nausea, tremors or rapid heart beat) manifestations. Results also suggest that dyslexics in larger families (3-4 sibling families) experience greater stress in interactions with their peers, than those in smaller families (two sibling families)--possibly from unfair sibling comparison. Copyright (c) 2007 John Wiley & Sons, Ltd.

  1. Effect of Reinforcement on Early-Age Concrete Temperature Stress: Preliminary Experimental Investigation and Analytical Simulation

    Directory of Open Access Journals (Sweden)

    Jianda Xin

    2015-01-01

    Full Text Available For concrete under short-term loading, effect of reinforcement on concrete crack resistance capability is usually negligible; however, recent research results show that extension of this viewpoint to concrete under long-term loading (temperature variation may be unsuitable. In order to investigate this phenomenon, this paper presents the experimental and analytical results of early-age reinforced concrete temperature stress development under uniaxial restraint. The experiments were carried out on a temperature stress testing machine (TSTM. Experimental results show that the coupling of reinforcement and concrete creep behavior influenced the concrete temperature stress development, and nearly 16% of concrete stress was reduced in the current research. Moreover, the cracking time of reinforced concrete was also delayed. Finally, based on the principle of superposition, analytical simulations of effect of reinforcement on concrete temperature stress have been performed.

  2. Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

    Science.gov (United States)

    Chalil, Sreeda; Pierre, Nicolas; Bakker, Astrid D; Manders, Ralph J; Pletsers, Annelies; Francaux, Marc; Klein-Nulend, Jenneke; Jaspers, Richard T; Deldicque, Louise

    2015-12-25

    Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging.

  3. Influence of Perceived Stress on Incident Amnestic Mild Cognitive Impairment: Results From the Einstein Aging Study.

    Science.gov (United States)

    Katz, Mindy J; Derby, Carol A; Wang, Cuiling; Sliwinski, Martin J; Ezzati, Ali; Zimmerman, Molly E; Zwerling, Jessica L; Lipton, Richard B

    2016-01-01

    Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI). Our objective is to determine whether perceived stress predicts incident aMCI and to determine if the influence of stress on aMCI is independent of known aMCI risk factors, particularly demographic variables, depression, and apolipoprotein genotype. The Einstein Aging Study is a longitudinal community-based study of older adults. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants (N=507; 71 developed incident aMCI; mean follow-up time=3.6 y, SD=2.0) who were aged 70 years and older, free of aMCI and dementia at baseline PSS administration, and had at least 1 subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset adjusting for covariates. High levels of perceived stress are associated with a 30% greater risk of incident aMCI (per 5-point increase in PSS: hazard ratio=1.30; 95% confidence interval, 1.08-1.58) independent of covariates. The consistency of results after covariate adjustment and the lack of evidence for reverse causation in longitudinal analyses suggest that these findings are robust. Understanding of the effect of perceived stress on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer dementia.

  4. Resilience, work engagement and stress reactivity in a middle-aged manual worker population.

    Science.gov (United States)

    Black, Julie K; Balanos, George M; Whittaker Previously Phillips, Anna C

    2017-06-01

    Work stress is a growing problem in Europe. Together, the negative physiological effect of stress on health, and increasing age increases the risk of developing cardiovascular disease in those aged over 50years. Therefore, identifying older workers who may be at risk of work-related stress, and its physiological effects, is key to promoting their health and wellbeing in the workforce. The present study examined the relationship between perceived psychological resilience and work-related factors (work engagement and presenteeism) and the physiological response to acute psychological stress in older manual workers in the UK. Thirty-one participants, mean (SD) age 54.9 (3.78)years reported perceived levels of resilience, work engagement, and presenteeism using standardized questionnaires. Cardiovascular measurements (heart rate (HR) and blood pressure (BP) and salivary cortisol were used to assess their physiological response to an acute psychological stress task. Resilience was not associated with work-related factors or reactivity. However, workers with higher work engagement showed lower SBP (p=0.02) and HR (p=0.001) reactivity than those with lower work engagement. Further, those with higher sickness presenteeism also had higher HR reactivity (p=0.03). This suggests a potential pathway by which higher work stress might contribute to the risk of future cardiovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Influence of age and length of service on the level of stress and burnout syndrome.

    Science.gov (United States)

    Stanetić, Kosana; Tesanović, Gordana

    2013-01-01

    The burnout syndrome is a response to chronic emotional and interpersonal stressors which are related to workplace. Medicine is one of the professions at the greatest risk of suffering from burnout syndrome. The aim of this study was to assess the presence of stress and burnout syndrome in relation with age and length of service in the family medicine physicians in the Republic of Srpska. The study was carried out on the basis of a questionnaire survey among family medicine physicians in seven Primary Health Care Centres in the Republic of Srpska from February 1st to April 30th 2010. The participants fulfilled the questionnaire for self-assessment of stress level and the Maslach Burnout Inventory, which were amended with data regarding age, sex, length of service and educational and vocational level. The study included 199 (83.3%) female and 40 (16.7%) male participants. The physicians aged over 46 years and with the length of service over 21 years had statistically significant higher level of stress and emotional exhaustion than younger participants and participants with shorter length of service. Age and length of service have important influence on the level of stress and burnout syndrome: the older the physicians and the higher the length of service the higher the level of stress and the higher the risk of burnout syndrome.

  6. Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress.

    Science.gov (United States)

    Gavilán, Elena; Pintado, Cristina; Gavilan, Maria P; Daza, Paula; Sánchez-Aguayo, Inmaculada; Castaño, Angélica; Ruano, Diego

    2015-05-01

    Autophagy plays a key role in the maintenance of cellular homeostasis, and autophagy deregulation gives rise to severe disorders. Many of the signaling pathways regulating autophagy under stress conditions are still poorly understood. Using a model of proteasome stress in rat hippocampus, we have characterized the functional crosstalk between the ubiquitin proteasome system and the autophagy-lysosome pathway, identifying also age-related modifications in the crosstalk between both proteolytic systems. Under proteasome inhibition, both autophagy activation and resolution were efficiently induced in young but not in aged rats, leading to restoration of protein homeostasis only in young pyramidal neurons. Importantly, proteasome stress inhibited glycogen synthase kinase-3β in young but activated in aged rats. This age-related difference could be because of a dysfunction in the signaling pathway of the insulin growth factor-1 under stress situations. Present data highlight the potential role of glycogen synthase kinase-3β in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.

  7. Tolerance to repeated stress in rats with lesions of the serotoninergic neurons of the Median Raphe Nucleus and chronically treated with imipramine.

    Science.gov (United States)

    Silva, K; Carvalho, M C; Padovan, C M

    2016-04-01

    Repeated exposure to aversive events leads to the development of tolerance to stress, which involves the serotonergic pathway originated in the Median Raphe Nucleus (MnRN) to the Dorsal Hippocampus (DH). However, it is not clear whether these lesion-induced deficits can be attenuated by treatment with antidepressants. Therefore, the aim of this work was to investigate the effects of chronic treatment with Imipramine (IMI) in rats with lesions in the MnRN and exposed to restraint stress. Male Wistar rats with or without neurochemical lesions of the MnRN serotonergic neurons with the neurotoxin 5,7-DHT were submitted to acute (2h) or chronic restraint (2h/day/seven consecutive days) and treated with saline (1 ml/kg) or imipramine (15 mg/kg) via intraperitoneal twice a day during the same period. In acutely restrained rats, stress occurred on the last day of treatment. Test in the elevated plus maze (EPM) was performed 24h later. After EPM test, animals were sacrificed and had their brains removed. Dorsal hippocampus and striatum were dissected and the levels of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) measured by HPLC analysis. Our results showed that in control rats exposure to acute restraint stress decreased exploration of the open and enclose arms of the EPM, an effect that was attenuated by imipramine. In rats with 5,7-DHT lesions, acute restraint did not change the exploration of the EPM, independently of the treatment. On the other hand, when chronically restrained, saline treated rat with 5,7-DHT lesion showed a reduced exploration of the open arms of the EPM. This effect was attenuated by simultaneous treatment with imipramine. HPLC analysis showed significantly decreases on 5-HT and 5-HIAA levels in the hippocampus, but not in the striatum. These later results confirm that 5,7-DHT lesions of the MnRN had significant impact on the serotonergic projections to the dorsal hippocampus which seems to be essential for the development of tolerance to repeated

  8. Shared signatures of social stress and aging in peripheral blood mononuclear cell gene expression profiles.

    Science.gov (United States)

    Snyder-Mackler, Noah; Somel, Mehmet; Tung, Jenny

    2014-10-01

    Chronic social stress is a predictor of both aging-related disease and mortality risk. Hence, chronic stress has been hypothesized to directly exacerbate the process of physiological aging. Here, we evaluated this hypothesis at the level of gene regulation. We compared two data sets of genome-wide gene expression levels in peripheral blood mononuclear cells (PBMCs): one that captured aging effects and another that focused on chronic social stress. Overall, we found that the direction, although not necessarily the magnitude, of significant gene expression changes tends to be shared between the two data sets. This overlap was observable at three levels: (i) individual genes; (ii) general functional categories of genes; and (iii) molecular pathways implicated in aging. However, we also found evidence that heterogeneity in PBMC composition limits the power to detect more extensive similarities, suggesting that our findings reflect an underestimate of the degree to which age and social stress influence gene regulation in parallel. Cell type-specific data on gene regulation will be important to overcome this limitation in the future studies.

  9. Age-experience changes of functional stress and work capability of miners with physical labor

    Energy Technology Data Exchange (ETDEWEB)

    Soldakm, I.I.

    1987-06-01

    Examines relation of functional stress and work capability to age and period of service of miners. Through time and motion studies work stress was measured by frequency of pulse, and work capability by work produced in a period of time. Four groups of workers were studied: 2 groups aged 23-28 with 2-5 years experience and 2 groups aged 30-42 with 7-15 years experience. The first 2 members of each group were employed at mechanized tasks directing mining machines and mechanisms; the second members of the 2 groups performed manual and partly mechanical and manual tasks. Results of time and motion study measurements demonstrate that degree of functional stress of miners increases and work capability diminishes with age, length of service and heaviness of physical work. Mathematical models relating functional stress and work capability were developed having the form of a nonlinear regression based on a function that enables prediction of work capability depending on age, experience and physical workload. 13 refs.

  10. Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs

    Directory of Open Access Journals (Sweden)

    Florence Boyer

    2015-01-01

    Full Text Available Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE. This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

  11. Enhanced Giant Piezoresistance Performance of Sandwiched ZnS/Si/SiO2 Radial Heterostructure Nanotubes for Nonvolatile Stress Memory with Repeatable Writing and Erasing.

    Science.gov (United States)

    Cheng, Baochang; Xiong, Li; Cai, Qiangsheng; Shi, Haiping; Zhao, Jie; Su, Xiaohui; Xiao, Yanhe; Lei, Shuijin

    2016-12-21

    It is a challenge to realize nonvolatile stress-writing memory. Herein, we propose a strategy to construct rewritable stress information storage devices, consisting of deliberately designing individual sandwiched ZnS/Si/SiO2 radial heterostructure nanotubes synthesized by one-step thermal evaporation method. A bulk trap-related Poole-Frenkel hopping mechanism is proposed. Carriers are localized in a narrow bandgap Si intermediate layer; moreover, incorporated impurities and heterointerface defects can serve as charge trap centers or storage mediators. Compressive strain can induce trap barrier height to decrease at relatively low operation bias voltage, whereas tensile strain can induce it to increase, resulting in a giant piezoresistance effect. After both loading compressive and tensile strains at low bias voltage, additionally, the emptying of trap states results in a high resistance state. However, the emptied trap states can be filled by applying a relatively high bias voltage without strains and, correspondingly, the memories return to low resistance state. The emptying and filling of trap states, respectively applied by strains and high electric field, result in a repeatable writing/erasing nonvolatile memory effect. The results indicate that the creation and modification of trap states in multiscale nanostructures can give an avenue to the development of novel nanodevices for rewritable nonvolatile stress sensor and memory.

  12. Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.

    Directory of Open Access Journals (Sweden)

    Nada M Porter

    Full Text Available BACKGROUND: Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. METHODOLOGY/PRINCIPAL FINDINGS: F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES, and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD-aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. CONCLUSIONS/SIGNIFICANCE: We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular

  13. Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.

    Science.gov (United States)

    Porter, Nada M; Bohannon, Julia H; Curran-Rauhut, Meredith; Buechel, Heather M; Dowling, Amy L S; Brewer, Lawrence D; Popovic, Jelena; Thibault, Veronique; Kraner, Susan D; Chen, Kuey Chu; Blalock, Eric M

    2012-01-01

    Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES), and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD-aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter effects of SD in young

  14. Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin.

    Science.gov (United States)

    Gómez-Pinilla, Pedro J; Pozo, Maria J; Camello, Pedro J

    2007-08-01

    The incidence of urinary bladder disturbances increases with age, and free radical accumulation has been proposed as a causal factor. Here we investigated the association between changes in bladder neuromuscular function and oxidative stress in aging and the possible benefits of melatonin treatment. Neuromuscular function was assessed by electrical field stimulation (EFS) of isolated guinea pig detrusor strips from adult and aged female guinea pigs. A group of adult and aged animals were treated with 2.5 mg x kg(-1) x day(-1) melatonin for 28 days. Neurotransmitter blockers were used to dissect pharmacologically the EFS-elicited contractile response. EFS induced a neurogenic and frequency-dependent contraction that was impaired by aging. This impairment is in part related to a decrease in detrusor myogenic contractility. Age also decreased the sensitivity of the contraction to pharmacological blockade of purinergic and sensitive fibers but increased the effect of blockade of nitrergic and adrenergic nerves. The density of cholinergic and nitrergic nerves remained unaltered, but aging modified afferent fibers. These changes were associated with an increased level of markers for oxidative stress. Melatonin treatment normalized oxidative levels and counteracted the aging-associated changes in bladder neuromuscular function. In conclusion, these results show that aging modifies neurogenic contraction and the functional profile of the urinary bladder plexus and simultaneously increases the oxidative damage to the organ. Melatonin reduces oxidative stress and improves the age-induced changes in bladder neuromuscular function, which could be of importance in reducing the impact of age-related bladder disorders.

  15. Complex interplay between health and successful aging: role of perceived stress, resilience, and social support.

    Science.gov (United States)

    Moore, Raeanne C; Eyler, Lisa T; Mausbach, Brent T; Zlatar, Zvinka Z; Thompson, Wesley K; Peavy, Guerry; Fazeli, Pariya L; Jeste, Dilip V

    2015-06-01

    Psychological and psychosocial resources, including resilience and social support, have traditionally been studied in the context of the stress paradigm and, more recently, in the context of successful aging. This study used moderated mediation analyses to examine the role of perceived stress in the relationships between physical and mental health functioning and self-rated successful aging (SRSA) and whether differences between people in level of resilience and social support changes the role of perceived stress in these relationships. A cross-sectional study of 1,006 older adults (mean age: 77 years) completed scales addressing SRSA, physical and mental health functioning, perceived stress, resilience, and social support. Results indicated that the strength of relationships between both physical and mental health functioning and SRSA were reduced after accounting for variation in level of perceived stress. The role of perceived stress in the association between mental health functioning and SRSA was found to be stronger among participants with the highest levels of resilience, and the influence of perceived stress on the degree of relationship between physical health functioning and SRSA was stronger among those with greatest social support. These findings suggest that interventions to reduce perceived stress may help break the link between disability and poor well-being in older adults. The findings further suggest that the impact of such interventions might differ depending on psychological resources (i.e., resilience) for mental health disabilities and external resources (i.e., social support) for those with physical health problems. The complex interplay of these factors should be taken into account in clinical settings.

  16. Age- and sex-dependent effects of early life stress on hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Manila eLoi

    2014-02-01

    Full Text Available Early life stress is a well-documented risk factor for the development of psychopathology in genetically predisposed individuals. As it is hard to study how early life stress impacts human brain structure and function, various animal models have been developed to address this issue. The models discussed here reveal that perinatal stress in rodents exerts lasting effects on the stress system as well as on the structure and function of the brain. One of the structural parameters strongly affected by perinatal stress is adult hippocampal neurogenesis. Based on compiled literature data, we report that postnatal stress slightly enhances neurogenesis until the onset of puberty in male rats; when animals reach adulthood, neurogenesis is reduced as a consequence of perinatal stress. By contrast, female rats showed a prominent reduction in neurogenesis prior to the onset of puberty, but this effect subsides when animals reach young adulthood. We further present preliminary data that transient treatment with a glucocorticoid receptor antagonist can normalize cell proliferation in maternally deprived female rats, while the compound had no effect in non-deprived rats. Taken together, the data show that neurogenesis is affected by early life stress in an age-and sex-dependent manner and that normalization may be possible during critical stages of brain development.

  17. Effects of stress hormones on the brain and cognition: Evidence from normal to pathological aging

    Directory of Open Access Journals (Sweden)

    Juliana Nery de Souza-Talarico

    Full Text Available Abstract Several studies have demonstrated a wide cognitive variability among aged individuals. One factor thought to be associated with this heterogeneity is exposure to chronic stress throughout life. Animal and human evidence demonstrates that glucocorticoids (GCs, the main class of stress hormones, are strongly linked to memory performance whereby elevated GC levels are associated with memory performance decline in both normal and pathological cognitive aging. Accordingly, it is believed that GCs may increase the brain's vulnerability to the effects of internal and external insults, and thus may play a role in the development of age-related cognitive disorders such as Alzheimer's disease (AD. The aim of this review article was to investigate the effects of GCs on normal and pathological cognitive aging by showing how these hormones interact with different brain structures involved in cognitive abilities, subsequently worsen memory performance, and increase the risk for developing dementia.

  18. Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

    DEFF Research Database (Denmark)

    Blažek, Radim; Polačik, Matej; Kačer, Petr

    2016-01-01

    to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

  19. Photoelastic stress analysis assisted evaluation of fracture toughness in hydrothermally aged epoxies

    Directory of Open Access Journals (Sweden)

    G. Pitarresi

    2014-10-01

    Full Text Available The present work has investigated the fracture toughness of a model DGEBA epoxy system subject to Hidro-Thermal aging. A Photoelastic Stress Analysis technique has been implemented, showing the evolution of stresses arising throughout the water uptake process due to the non-uniform swelling of the material. Gravimetric and Dynamic Mechanical Thermal Analyses have further complemented the characterization, showing the onset of plasticization effects with aging. The correlation of all previous characterizations has allowed to conclude that an increase of KIC fracture toughness is obtained at the fully saturated condition. In particular Photoelasticity has also revealed the onset of relevant swelling induced stresses during the first stages of water absorption, leading to an increase of fracture toughness due to compressive stresses settling near the crack tip. A stress free condition is instead reestablished at the later stages of absorption, suggesting that the increased toughness of the saturated material is an effect of the modifications induced by aging on the polymer structure.

  20. Stress in childhood, adolescence and early adulthood, and cortisol levels in older age.

    Science.gov (United States)

    Harris, Mathew A; Cox, Simon R; Brett, Caroline E; Deary, Ian J; MacLullich, Alasdair M J

    2017-03-01

    The glucocorticoid hypothesis suggests that overexposure to stress may cause permanent upregulation of cortisol. Stress in youth may therefore influence cortisol levels even in older age. Using data from the 6-Day Sample, we investigated the effects of high stress in childhood, adolescence and early adulthood - as well as individual variables contributing to these measures; parental loss, social deprivation, school and home moves, illness, divorce and job instability - upon cortisol levels at age 77 years. Waking, waking +45 min (peak) and evening salivary cortisol samples were collected from 159 participants, and the 150 who were not using steroid medications were included in this study. After correcting for multiple comparisons, the only significant association was between early-adulthood job instability and later-life peak cortisol levels. After excluding participants with dementia or possible mild cognitive impairment, early-adulthood high stress showed significant associations with lower evening and mean cortisol levels, suggesting downregulation by stress, but these results did not survive correction for multiple comparisons. Overall, our results do not provide strong evidence of a relationship between stress in youth and later-life cortisol levels, but do suggest that some more long-term stressors, such as job instability, may indeed produce lasting upregulation of cortisol, persisting into the mid-to-late seventies.

  1. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes

    Indian Academy of Sciences (India)

    Finny Monickaraj; Sankaramoorthy Aravind; Pichamoorthy Nandhini; Paramasivam Prabu; Chandrakumar Sathishkumar; Viswanathan Mohan; Muthuswamy Balasubramanyam

    2013-03-01

    Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.

  2. The Effects of Repeated Reading on the Fluency and Comprehension Skills of Elementary-Age Students with Learning Disabilities (LD), 2001-2011: A Review of Research and Practice

    Science.gov (United States)

    Strickland, Whitney D.; Boon, Richard T.; Spencer, Vicky G.

    2013-01-01

    This article provides an extensive review of the literature on the use of repeated reading to improve the reading fluency and comprehension skills of elementary-age students with learning disabilities. A systematic review of the published literature from 2001 to 2011 was conducted and nineteen (N = 19) research-based repeated reading studies were…

  3. Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice.

    Science.gov (United States)

    Vida, Carmen; de Toda, Irene Martínez; Cruces, Julia; Garrido, Antonio; Gonzalez-Sanchez, Mónica; De la Fuente, Mónica

    2017-08-01

    The age-related changes in the immune functions (immunosenescence) may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the "oxidation-inflammation" theory of aging proposes that phagocytes are the main immune cells contributing to "oxi-inflamm-aging", this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation ("a hallmark of aging"), in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively) were used. The xanthine oxidase (XO) activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG) and reduced (GSH) glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels), higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels) and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and "oxi-inflamm-aging". Moreover, the determination of oxidative stress and

  4. Developing Physiologic Stress Profiles for School-Age Children Who Stutter

    Science.gov (United States)

    Ortega, Aishah Y.; Ambrose, Nicoline G.

    2011-01-01

    Purpose: Physiologic reactivity profiles were generated for 9 school-age children with a history of stuttering. Utilizing salivary sampling, stress biomarkers cortisol and alpha-amylase were measured in response to normal daily stressors. Children with a history of stuttering were characterized as high or low autonomic reactors when compared to…

  5. STRESS BURDEN IN WOMEN IN REPRODUCTIVE AGE IN SLOVENIA – SOME CAUSES AND CONSEQUENCES

    Directory of Open Access Journals (Sweden)

    Majda Pahor

    2009-06-01

    Conclusions Public health activities to reduce stress burden among women in reproductive age in Slovenia (e.g. changes of legislation, changes of workplace behaviour should be focused on women with lowest education and of lowest social class, especially working in heavy industry, and on employed women with highest education.

  6. Parenthood, Stress, and Mental Health in Late Midlife and Early Old Age

    Science.gov (United States)

    Pudrovska, Tetyana

    2009-01-01

    Using 2 waves of the Wisconsin Longitudinal Study, I examine psychological consequences of potentially stressful, non-normative, or "off-time" aspects of the parental role in late midlife and early old age, including coresidence with adult children, stepparenthood, and parental bereavement. Additionally, I analyze gender differences in…

  7. Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle

    DEFF Research Database (Denmark)

    Hütter, Eveline; Skovbro, Mette; Lener, Barbara;

    2007-01-01

    According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain....... However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated...... from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high-resolution respirometry, and ROS production was analyzed by in situ staining with the redox-sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional...

  8. Reflections on the Theories of Aging, of Oxidative Stress, and of Science in General. Is It Time to Abandon the Free Radical (Oxidative Stress) Theory of Aging?

    Science.gov (United States)

    Liochev, Stefan I

    2015-07-20

    Aging and oxidative stress are complex phenomena, and their understanding is of enormous theoretical and practical significance. Numerous hypotheses and theories that attempt to explain these phenomena have been developed. These hypotheses and theories compete with each other, with each claiming to be the correct one, while significantly contradicting each other. It is important to develop a maximally correct theory that may then trigger significant practical breakthroughs. None of these theories is entirely correct or close enough to the truth. However, most of them contain many correct elements (CE). Finding these CE is possible by analysis of these theories. Once the CE are found, they can be merged by synthesis in a better new theory. An analysis of some of the theories of aging followed by synthesis is attempted.

  9. Effects of thermal aging and stress triaxiality on PWSCC initiation susceptibility of nickel-based Alloy 600

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seung Chang; Choi, Kyoung Joon; Kim, Tae Ho; Kim, Ji Hyun [Dept. of Nuclear Science and Engineering, School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology, Ulsan (Korea, Republic of)

    2016-10-15

    In present study, effects of thermal aging and triaxial stress were investigated in terms of primary water stress corrosion cracking susceptibility. The thermal aging was applied via heat treatment at 400°C and triaxial stress was applied via notched tensile test specimen. The crack initiation time of each specimen were then measured by direct current potential drop method during slow strain rate test at primary water environment. Alloys with 10 years thermal aging exhibited the highest susceptibility to stress corrosion cracking and asreceived specimen shows lowest susceptibility. The trend was different with triaxial stress applied; 20 years thermal aging specimen shows highest susceptibility and as-received specimen shows lowest. It would be owing to change of precipitate morphology during thermal aging and different activated slip system in triaxial stress state.

  10. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    Directory of Open Access Journals (Sweden)

    Mika Reinisalo

    2015-01-01

    Full Text Available Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD, and Alzheimer’s disease (AD. In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2 mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed.

  11. Long-range correlations and fractal dynamics in C. elegans: Changes with aging and stress

    Science.gov (United States)

    Alves, Luiz G. A.; Winter, Peter B.; Ferreira, Leonardo N.; Brielmann, Renée M.; Morimoto, Richard I.; Amaral, Luís A. N.

    2017-08-01

    Reduced motor control is one of the most frequent features associated with aging and disease. Nonlinear and fractal analyses have proved to be useful in investigating human physiological alterations with age and disease. Similar findings have not been established for any of the model organisms typically studied by biologists, though. If the physiology of a simpler model organism displays the same characteristics, this fact would open a new research window on the control mechanisms that organisms use to regulate physiological processes during aging and stress. Here, we use a recently introduced animal-tracking technology to simultaneously follow tens of Caenorhabdits elegans for several hours and use tools from fractal physiology to quantitatively evaluate the effects of aging and temperature stress on nematode motility. Similar to human physiological signals, scaling analysis reveals long-range correlations in numerous motility variables, fractal properties in behavioral shifts, and fluctuation dynamics over a wide range of timescales. These properties change as a result of a superposition of age and stress-related adaptive mechanisms that regulate motility.

  12. Shape Memory Behavior of [111]-Oriented NiTi Single Crystals After Stress-Assisted Aging

    Institute of Scientific and Technical Information of China (English)

    Irfan Kaya; Hirobumi Tobe; Haluk Ersin Karaca; Emre Acar; Yuriy Chumlyakov

    2016-01-01

    The shape memory behavior of [111]-oriented NistTi49 (at.%) single crystals was investigated after stressassisted aging at 500 ℃ for 1.5 h under a compressive stress of-150 MPa.It was found that a single family of Ni4Ti3 precipitates with two crystallographically equivalent variants was formed after aging under compressive stress.Stressassisted aging resulted in tensile two-way shape memory effect strain of 1.56% under-5 MPa.Thermal cycling under -600 MPa resulted in a transformation strain of-2.15%,while the subsequent thermal cycling under-5 MPa resulted in a tensile two-way shape memory effect strain of 2.2%.

  13. Stress corrosion cracking resistance of aluminum alloy 7000 series after two-step aging

    Directory of Open Access Journals (Sweden)

    Jegdić Bore V.

    2015-01-01

    Full Text Available The effect of one step-and a new (short two-step aging on the resistance to stress corrosion cracking of an aluminum alloy 7000 series was investigated, using slow strain rate test and fracture mechanics method. Aging level in the tested alloy was evaluated by means of scanning electron microscopy and measurements of electrical resistivity. It was shown that the alloy after the new two-step aging is significantly more resistant to stress corrosion cracking. Values of tensile properties and fracture toughness are similar for both thermal states. Processes that take place at the crack tip have been considered. The effect of the testing solution temperature on the crack growth rate on the plateau was determined. Two values of the apparent activation energy were obtained. These values correspond to different processes that control crack growth rate on the plateau at higher and lower temperatures. [Projekat Ministarstva nauke Republike Srbije, br. TR 34028 i br. TR 34016

  14. Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process.

    Science.gov (United States)

    Yokozawa, Takako; Kim, Hyun Young; Kim, Hyun Ju; Okubo, Tsutomu; Chu, Djoing-Chi; Juneja, Lekh Raj

    2007-06-01

    Amla (Emblica officinalis Gaertn.) is widely used in Indian medicine for the treatment of various diseases. We have investigated the effects of amla on the lipid metabolism and protein expression involved in oxidative stress during the ageing process. SunAmla or ethyl acetate extract of amla, a polyphenol-rich fraction, was administered at a dose of 40 or 10 mg/kg body weight per d for 100 d to young rats aged 2 months and aged rats aged 10 months. The lipid levels, such as cholesterol and TAG, in serum and liver were markedly elevated in aged control rats, while they were significantly decreased by the administration of amla. The PPARalpha is known to regulate the transcription of genes involved in lipid and cholesterol metabolism. The PPARalpha protein level in liver was reduced in aged control rats. However, the oral administration of amla significantly increased the hepatic PPARalpha protein level. In addition, oral administration of amla significantly inhibited the serum and hepatic mitochondrial thiobarbituric acid-reactive substance levels in aged rats. Moreover, the elevated expression level of bax was significantly decreased after the oral administration of amla, while the level of bcl-2 led to a significant increase. Furthermore, the expressions of hepatic NF-kappaB, inducible NO synthase (iNOS), and cyclo-oxygenase-2 (COX-2) protein levels were also increased with ageing. However, amla extract reduced the iNOS and COX-2 expression levels by inhibiting NF-kappaB activation in aged rats. These results indicate that amla may prevent age-related hyperlipidaemia through attenuating oxidative stress in the ageing process.

  15. Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals.

    Science.gov (United States)

    Schwörer, Simon; Becker, Friedrich; Feller, Christian; Baig, Ali H; Köber, Ute; Henze, Henriette; Kraus, Johann M; Xin, Beibei; Lechel, André; Lipka, Daniel B; Varghese, Christy S; Schmidt, Manuel; Rohs, Remo; Aebersold, Ruedi; Medina, Kay L; Kestler, Hans A; Neri, Francesco; von Maltzahn, Julia; Tümpel, Stefan; Rudolph, K Lenhard

    2016-12-15

    The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell function during ageing, but the nature of this process remains poorly understood. Hox genes are key regulators of stem cells and tissue patterning during embryogenesis with an unknown role in ageing. Here we show that the epigenetic stress response in muscle stem cells (also known as satellite cells) differs between aged and young mice. The alteration includes aberrant global and site-specific induction of active chromatin marks in activated satellite cells from aged mice, resulting in the specific induction of Hoxa9 but not other Hox genes. Hoxa9 in turn activates several developmental pathways and represents a decisive factor that separates satellite cell gene expression in aged mice from that in young mice. The activated pathways include most of the currently known inhibitors of satellite cell function in ageing muscle, including Wnt, TGFβ, JAK/STAT and senescence signalling. Inhibition of aberrant chromatin activation or deletion of Hoxa9 improves satellite cell function and muscle regeneration in aged mice, whereas overexpression of Hoxa9 mimics ageing-associated defects in satellite cells from young mice, which can be rescued by the inhibition of Hoxa9-targeted developmental pathways. Together, these data delineate an altered epigenetic stress response in activated satellite cells from aged mice, which limits satellite cell function and muscle regeneration by Hoxa9-dependent activation of developmental pathways.

  16. Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

    Directory of Open Access Journals (Sweden)

    Adam B. Salmon

    2016-07-01

    Full Text Available Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition.

  17. Analysis of Age Dependent Effects of Heat Stress on EEG Frequency Components in Rats

    Institute of Scientific and Technical Information of China (English)

    RAKESH KUMAR SINHA

    2009-01-01

    Objective To demonstrate changes in different frequencies of cerebral electrical activity or electroencephalogram (EEG) following exposure to high environmental heat in three different age groups of freely moving rats. Methods Rats were divided into three groups (i) acute heat stress - subjected to a single exposure for four hours at 38 ℃; (ii) chronic heat stress -exposed for 21 days daily for one hour at 38 ℃, and (iii) handling control groups. The digital polygraphic sleep-EEG recordings were performed just after the heat exposure from acute stressed rats and on 22nd day from chronic stressed rats by simultaneous recording of cortical EEG EOG (electrooculogram), and EMG (electromyogram). Further, power spectrum analyses were performed to analyze the effects of heat stress. Results The frequency analysis of EEG signals following exposure to high environmental heat revealed that in all three age groups of rats, changes in higher frequency components (β2) were significant in all sleep-wake states following both acute and chronic heat stress conditions. After exposure to acute heat, significant changes in EEG frequencies with respect to their control groups were observed, which were reversed partly or fully in four hours of EEG recording. On the other hand, due to repetitive chronic exposure to hot environment, adaptive and long-term changes in EEG frequency patterns were observed. Conclusion The present study has exhibited that the cortical EEG is sensitive to environmental heat and alterations in EEG frequencies in different sleep-wake states due to heat stress can be differentiated efficiently by EEG power spectrum analysis.

  18. Spectral-domain Optical Coherence Tomography Retinal and Choroidal Thickness Metric Repeatability in Age-related Macular Degeneration

    DEFF Research Database (Denmark)

    Hanumunthadu, Daren; Ilginis, Tomas; Restori, Marie

    2016-01-01

    ) macular subfields. Center point thickness and total macular volume were also included in the analysis. Manual subfoveal choroidal thickness measurements were made by a masked observer. RESULTS: A total of 40 eyes of 40 patients were included in this analysis (mean [± standard deviation] age: 74.1 [± 7...... for the center point was 47.5 μm (95% CI 46.2-48.7 μm). Images were also reviewed for the presence of segmentation error in the central macular subfield, and after exclusion of these eyes the revised CR for this subfield was 13.7 μm (95% CI 13.3-14.1 μm). The intrasession CR of subfoveal choroidal thickness...... was 34.7 μm (95% CI 33.7-35.7 μm). CONCLUSIONS: This study suggests that a change of greater than 31 μm in Spectralis SDOCT-derived retinal thickness measurement of the central macular subfield and 35 μm in subfoveal choroidal thickness is necessary to detect true clinical change associated with disease...

  19. Aging and the HPA axis: Stress and resilience in older adults.

    Science.gov (United States)

    Gaffey, Allison E; Bergeman, C S; Clark, Lee Anna; Wirth, Michelle M

    2016-09-01

    Hypothalamic-pituitary-adrenal (HPA) axis function may change over the course of aging, and altered diurnal or stress-induced secretion of the hormone cortisol could predispose older adults to negative health outcomes. We propose that psychological resilience may interact with diurnal cortisol to affect health outcomes later in life. Emotion regulation and social support are two constructs that contribute to resilience and exhibit age-specific patterns in older adults. Determining how the use of resilience resources interacts with age-related diurnal cortisol will improve our understanding of the pathways between stress, resilience, and well-being. In this review, we assess published studies evaluating diurnal cortisol in older adults to better understand differences in their HPA axis functioning. Evidence thus far suggests that diurnal cortisol may increase with age, although cross-sectional studies limit the conclusions that can be drawn. We also review extant evidence connecting age-specific signatures of emotion regulation and social support with diurnal cortisol. Conclusions are used to propose a preliminary model demonstrating how resilience resources may modulate the effects of cortisol on health in aging.

  20. Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice.

    Science.gov (United States)

    Al-Amin, Md Mamun; Hasan, S M Nageeb; Alam, Tanzir; Hasan, Ahmed Tasdid; Hossain, Imran; Didar, Rohini Rowshan; Alam, Md Ashraful; Rahman, Md Mahbubur

    2014-12-15

    Tadalafil, a type-5 phosphodiesterase enzyme inhibitor with long half-life used to treat erectile dysfunction. Recently it has been reported that tadalafil improves cognitive function. Here, we aimed to investigate the age dependent effects of tadalafil on memory, locomotor, behavior, and oxidative stress in the hippocampus. Tadalafil was orally administered everyday (5 mg/kg) to young (2 months) and old (16 months) healthy mice for 4 weeks. Control mice from each group received equal volume of 0.9% normal saline for the same duration. Memory and locomotor activity were tested using radial arm maze and open field test respectively. The level of malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was analyzed and catalase activity was determined from the isolated hippocampus. Treatment with tadalafil in aged mice improves working memory than the corresponding tadalafil treated young mice in radial arm maze test. Tadalafil treated mice traveled less distance in the center and the mean speed of tadalafil treated aged mice was significantly lower than the tadalafil treated young mice in open field test. Tadalafil treatment elicited a decrease of MDA level in the hippocampus of aged mice than that of young mice. APOP level was decreased only in aged mice treated with tadalafil. Treatment with tadalafil decreased NO and increased catalase activity in both young and aged mice. On the basis of previous and our findings, we conclude that tadalafil treatment reduces oxidative stress while increased cGMP level in the hippocampus might be responsible for memory enhancement.

  1. Functional changes of the coronary microvasculature with aging regarding glucose tolerance, energy metabolism, and oxidative stress.

    Science.gov (United States)

    Mourmoura, Evangelia; Couturier, Karine; Hininger-Favier, Isabelle; Malpuech-Brugère, Corinne; Azarnoush, Kasra; Richardson, Melanie; Demaison, Luc

    2014-01-01

    This study was aimed at characterizing the functional progression of the endothelial (ECs) and smooth muscle cells (SMCs) of the coronary microvasculature between youth and old age, as well as at determining the mechanisms of the observed changes on the basis of the glucose tolerance, mitochondrial energy metabolism, and oxidative stress. Male rats were divided into four age groups (3, 6, 11, and 17 months for the young (Y), young adult (YA), middle-aged (MA), and old (O) animals). The cardiac mechanical function, endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the coronary microvasculature were determined in a Langendorff preparation. The mitochondrial respiration and H2O2 production were evaluated and completed by ex vivo measurements of oxidative stress. EDD progressively decreased from youth to old age. The relaxation properties of the SMCs, although high in the Y rats, decreased drastically between youth and young adulthood and stabilized thereafter, paralleling the reduction of mitochondrial oxidative phosphorylation. The ECs dilatation activity, low at youth, was stimulated in YA animals and returned to their initial level at middle age. That parameter followed faithfully the progression of the amount of active cardiac endothelial nitric oxide synthase and whole body glucose intolerance. In conclusion, the progressive decrease in EDD occurring with aging is due to different functional behaviors of the ECs and SMCs, which appear to be associated with the systemic glucose intolerance and cardiac energy metabolism.

  2. Evaluating the effectiveness of Washington state repeated job search services on the employment rate of prime-age female welfare recipients.

    Science.gov (United States)

    Hsiao, Cheng; Shen, Yan; Wang, Boqing; Weeks, Greg

    2008-07-01

    This paper uses an unbalanced panel dataset to evaluate how repeated job search services (JSS) and personal characteristics affect the employment rate of the prime-age female welfare recipients in the State of Washington. We propose a transition probability model to take into account issues of sample attrition, sample refreshment and duration dependence. We also generalize Honoré and Kyriazidou's [Honoré, B.E., Kyriazidou, E., 2000. Panel data discrete choice models with lagged dependent variables. Econometrica 68 (4), 839-874] conditional maximum likelihood estimator to allow for the presence of individual-specific effects. A limited information test is suggested to test for selection issues in non-experimental data. The specification tests indicate that the (conditional on the set of the confounding variables considered) assumptions of no selection due to unobservables and/or no unobserved individual-specific effects are not violated. Our findings indicate that the first job search service does have positive and significant impacts on the employment rate. However, providing repeated JSS to the same client has no significant impact. Further, we find that there are significant experience-enhancing effects. These findings suggest that providing one job search services training to individuals may have a lasting impact on raising their employment rates.

  3. Mozart versus new age music: relaxation states, stress, and ABC relaxation theory.

    Science.gov (United States)

    Smith, Jonathan C; Joyce, Carol A

    2004-01-01

    Smith's (2001) Attentional Behavioral Cognitive (ABC) relaxation theory proposes that all approaches to relaxation (including music) have the potential for evoking one or more of 15 factor-analytically derived relaxation states, or "R-States" (Sleepiness, Disengagement, Rested / Refreshed, Energized, Physical Relaxation, At Ease/Peace, Joy, Mental Quiet, Childlike Innocence, Thankfulness and Love, Mystery, Awe and Wonder, Prayerfulness, Timeless/Boundless/Infinite, and Aware). The present study investigated R-States and stress symptom-patterns associated with listening to Mozart versus New Age music. Students (N = 63) were divided into three relaxation groups based on previously determined preferences. Fourteen listened to a 28-minute tape recording of Mozart's Eine Kleine Nachtmusik and 14 listened to a 28-minute tape of Steven Halpern's New Age Serenity Suite. Others (n = 35) did not want music and instead chose a set of popular recreational magazines. Participants engaged in their relaxation activity at home for three consecutive days for 28 minutes a session. Before and after each session, each person completed the Smith Relaxation States Inventory (Smith, 2001), a comprehensive questionnaire tapping 15 R-States as well as the stress states of somatic stress, worry, and negative emotion. Results revealed no differences at Session 1. At Session 2, those who listened to Mozart reported higher levels of At Ease/Peace and lower levels of Negative Emotion. Pronounced differences emerged at Session 3. Mozart listeners uniquely reported substantially higher levels of Mental Quiet, Awe and Wonder, and Mystery. Mozart listeners reported higher levels, and New Age listeners slightly elevated levels, of At Ease/Peace and Rested/Refreshed. Both Mozart and New Age listeners reported higher levels of Thankfulness and Love. In summary, those who listened to Mozart's Eine Kleine Nachtmusik reported more psychological relaxation and less stress than either those who listened to

  4. AGE-INDEPENDENT, GREY-MATTER-LOCALIZED, BRAIN ENHANCED OXIDATIVE STRESS IN MALE FISCHER 344 RATS,1,2

    Science.gov (United States)

    While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex...

  5. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

    Directory of Open Access Journals (Sweden)

    Chunhu Gu

    Full Text Available Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1 is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo and aged (22-24 mo mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2, SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P<0.05. Exogenous toxic aldehydes (4-HNE exposure in isolated cardiomyocyte verified that aldehyde-induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse hypoxia/reoxygenation (H/R injury, which could all be rescued by Alda-1 (ALDH2 activator (all P<0.05. However, SIRT1 inhibitor blocked the protective effect of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher carbonylation but lower activity of SIRT1 in aged hearts than that seen in young hearts (P<0.05. The application of Alda-1 significantly reduced the carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury in aged hearts, but failed to protect Sirt1(+/- knockout mice against myocardial I/R injury. This was verified by Alda-1 treatment improved postischemic contractile function recovery in ex vivo perfused aged but not in Sirt1(+/- hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These results provide a new insight that impaired cardiac SIRT1 activity by carbonyl stress plays a critical role in the increased susceptibility of aged heart to I/R injury. ALDH2 activation can restore this aging-related myocardial ischemic intolerance.

  6. Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

    Science.gov (United States)

    Pujol-Lereis, Luciana M; Schäfer, Nicole; Kuhn, Laura B; Rohrer, Bärbel; Pauly, Diana

    2016-01-01

    Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye.

  7. Rosa26-GFP direct repeat (RaDR-GFP mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo.

    Directory of Open Access Journals (Sweden)

    Michelle R Sukup-Jackson

    2014-06-01

    Full Text Available Homologous recombination (HR is critical for the repair of double strand breaks and broken replication forks. Although HR is mostly error free, inherent or environmental conditions that either suppress or induce HR cause genomic instability. Despite its importance in carcinogenesis, due to limitations in our ability to detect HR in vivo, little is known about HR in mammalian tissues. Here, we describe a mouse model in which a direct repeat HR substrate is targeted to the ubiquitously expressed Rosa26 locus. In the Rosa26 Direct Repeat-GFP (RaDR-GFP mice, HR between two truncated EGFP expression cassettes can yield a fluorescent signal. In-house image analysis software provides a rapid method for quantifying recombination events within intact tissues, and the frequency of recombinant cells can be evaluated by flow cytometry. A comparison among 11 tissues shows that the frequency of recombinant cells varies by more than two orders of magnitude among tissues, wherein HR in the brain is the lowest. Additionally, de novo recombination events accumulate with age in the colon, showing that this mouse model can be used to study the impact of chronic exposures on genomic stability. Exposure to N-methyl-N-nitrosourea, an alkylating agent similar to the cancer chemotherapeutic temozolomide, shows that the colon, liver and pancreas are susceptible to DNA damage-induced HR. Finally, histological analysis of the underlying cell types reveals that pancreatic acinar cells and liver hepatocytes undergo HR and also that HR can be specifically detected in colonic somatic stem cells. Taken together, the RaDR-GFP mouse model provides new understanding of how tissue and age impact susceptibility to HR, and enables future studies of genetic, environmental and physiological factors that modulate HR in mammals.

  8. The effect of surgical and psychological stress on learning and memory function in aged C57BL/6 mice.

    Science.gov (United States)

    Zhang, C; Li, C; Xu, Z; Zhao, S; Li, P; Cao, J; Mi, W

    2016-04-21

    Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. We therefore established a pre-clinical model in aged C57BL/6 mice and aimed to investigate the effects of surgical stress and psychological stress on learning and memory function and the possible roles of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. The surgical stress was induced by abdominal surgery under local anesthesia, and the psychological stress was induced by a communication box. Cognitive functions and markers of the AKT/mTOR pathway were assessed at 1, 3 and 7 days following the stress. The impairments of learning and memory function existed for up to 7 days following surgical stress and surgical stress plus psychological stress, whereas the psychological stress did not affect the cognitive function alone or combined with surgical stress. Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD.

  9. Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging) of Escherichia coli.

    Science.gov (United States)

    Clark, Michelle W; Yie, Anna M; Eder, Elizabeth K; Dennis, Richard G; Basting, Preston J; Martinez, Keith A; Jones, Brian D; Slonczewski, Joan L

    2015-01-01

    Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH), no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5) the cells maintained cytoplasmic pH values at 7.2-7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress.

  10. Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging of Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Michelle W Clark

    Full Text Available Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH, no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5 the cells maintained cytoplasmic pH values at 7.2-7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress.

  11. Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

    Directory of Open Access Journals (Sweden)

    Courtney eScerbak

    2014-07-01

    Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

  12. Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.

    Science.gov (United States)

    Bonilha, Vera L; Bell, Brent A; Rayborn, Mary E; Samuels, Ivy S; King, Anna; Hollyfield, Joe G; Xie, Chengsong; Cai, Huaibin

    2017-03-01

    Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient in DJ-1, a protein that is thought to be important in protecting cells from oxidative stress. Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both group of aged mice, scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and i

  13. Can repeating glacial seismic events be used to monitor stress changes within the underlying volcano? -Case study from the glacier overlain Katla volcano, Iceland

    Science.gov (United States)

    Jonsdottir, K.; Vogfjord, K. S.; Bean, C. J.; Martini, F.

    2013-12-01

    individual families are usually clustered in time over several months, and sometimes families may reappear even up to several years later. Using families including many events and covering long periods (10-20 months) we compare the coda (the tail) of individual events within a family. This is repeated for all the surrounding stations. The analysis, coda wave interferometry (cwi) is a correlation method that builds on the fact that changes in stress in the edifice lead to changes in seismic velocities. The coda waves are highly sensitive to small stress changes. By using a repeating source, implying we have the same source mechanism and the same path, we can track temporal stress changes in the medium between the source and the receiver. Preliminary results from Katla suggest that by using the repeating glacial events and the coda wave interferometry technique we observe annual seismic velocity changes around the volcano of ca. 0.7%. We find that seismic velocities increase from January through July and decrease in August to December. These changes can be explained by pore-water pressure changes and/or loading and de-loading of the overlain glacier. We do not find immediate precursors for an impending eruption at Katla; however we now have a better understanding of its background seismicity.

  14. Thermal stress resistance and aging effects of Panax notoginseng polysaccharides on Caenorhabditis elegans.

    Science.gov (United States)

    Feng, Shiling; Cheng, Haoran; Xu, Zhou; Shen, Shian; Yuan, Ming; Liu, Jing; Ding, Chunbang

    2015-11-01

    Panax notoginseng attract public attention due to their potential biomedical properties and corresponding health benefits. The present study investigated the anti-aging and thermal stress resistance effects of polysaccharides from P. notoginseng on Caenorhabditis elegans. Results showed polysaccharides had little scavenging ability of reactive oxygen species (ROS) in vitro, but significantly extended lifespan of C. elegans, especially the main root polysaccharide (MRP) which prolongs the mean lifespan of wild type worms by 21%. Further study demonstrated that the heat stress resistance effect of polysaccharides on C. elegans might be attributed to the elevation of antioxidant enzyme activities (both superoxide dismutase (SOD) and catalase (CAT)) and the reduction lipid peroxidation of malondialdehyde (MDA) level. Taken together, the results provided a scientific basis for the further exploitation of the mechanism of longer lifespan controlled by P. notoginseng polysaccharides on C. elegans. The P. notoginseng polysaccharides might be considered as a potential source to delay aging.

  15. Audio Recorded Guided Imagery Method to Reduce Stress Hospitalisazation in School Age Children in Palu Hospital

    Directory of Open Access Journals (Sweden)

    Fitria Masulili

    2013-12-01

    Full Text Available Hospitalization is a condition of a person because of illness and hospital admission. Research objectives determine the influence of audio recorded guided imagery method to stress of hospitalization in school-age children in hospital in Palu. Quasi-experimental research design with pre and post test design with control group. The sample of children aged 7-12 years were 26 respondents intervention group and 26 control group respondents. Intervention is the method of audio recorded guided imagery, three times a day for two days (one session equal to15 minutes. The results showed the significant difference mean stress score of hospitalization after the intervention (Pv = 0.004. No contribution of confounding variables. Based on these results, audio recorded guided imagery intervention can be applied to care the sick pediatric in hospital.

  16. Stress serration and arch-shaped Lüders stress plateau behaviour of Ti-50.8 at% Ni wire prepared by selective electrical resistance over-aging

    Science.gov (United States)

    Meng, Qinglin; Wu, Zhigang; Bakhtiari, Reza; Zhang, Junsong; Yang, Hong; Liu, Yinong

    2016-11-01

    Joule heating of NiTi shape memory alloy wires is a commonly applied technique for heat treatment and shape setting in many applications. Another innovative use of this method is to produce functionally graded NiTi. In this study, NiTi wires with spatially varied shape memory characteristics along the length were created by electrical resistance over-aging of a Ni-rich superelastic NiTi alloy. The stress-strain behaviour of such wires exhibited some new and unique characteristics during the stress-induced martensitic transformation, including two discrete stress plateaus, stress serration during transition between the two stress plateaus and an arch-shaped stress plateau in the over-aged section. These unique features have direct implications to design using NiTi alloys and the underlying mechanisms are explained in this study.

  17. Recruitment of aged donor heart with pharmacological stress echo. A case report

    Directory of Open Access Journals (Sweden)

    Bombardini Tonino

    2006-01-01

    Full Text Available Abstract Background The heart transplant is a treatment of the heart failure, which is not responding to medications, and its efficiency is already proved: unfortunately, organ donation is a limiting step of this life-saving procedure. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease. Donors with a history of cardiac disease are generally excluded. Coronary angiography is recommended for most male donors older than 45 years and female donors older than 50 years to evaluate coronary artery stenoses. A simpler way to screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease should be stress echocardiography. Case report A marginal donor (A 57 year old woman meeting legal requirements for brain death underwent a transesophageal (TE Dipyridamole stress echo (6 minutes accelerated protocol to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at baseline and peak stress, without signs of stress inducible ischemia. The pressure/volume ratio was 9.6 mmHg/ml/m2 at baseline, increasing to 14 mmHg/ml/m2 at peak stress, demonstrating absence of latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient "marginal" for co-morbidity ( a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV. Postoperative treatment and early immunosuppressant regimen were performed according to standard protocols. The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant; left ventriculography showed normal global and segmental LV function of the transplanted heart. Conclusion For

  18. Stability analysis of a model gene network links aging, stress resistance, and negligible senescence.

    Science.gov (United States)

    Kogan, Valeria; Molodtsov, Ivan; Menshikov, Leonid I; Shmookler Reis, Robert J; Fedichev, Peter

    2015-08-28

    Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity. We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.

  19. Oxidative Stress and Mitochondrial Dysfunction in Down’s Syndrome: Relevance to Aging and Dementia

    OpenAIRE

    Coskun, Pinar E; Jorge Busciglio

    2012-01-01

    Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down’s syndrome (DS). Even though individuals with trisomy 21 exhibit a higher survival rate compared to other aneuploidies, most of them die in utero or early during postnatal life. While the survivors are currently predicted to live past 60 years, they suffer higher incidence of age-related conditions including Alzheimer’s disease (AD). This paper is centered on...

  20. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    OpenAIRE

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anythin...

  1. Effects of AGEs on Oxidation Stress and Antioxidation Abilities in Cultured Astrocytes

    Institute of Scientific and Technical Information of China (English)

    JIAN-MING JIANG; ZHEN WANG; DIAN-DONG LI

    2004-01-01

    Objective To investigate whether two kinds of in vitro prepared advanced glycation end products (AGEs), Glu-BSA and Gal-BSA, could change oxidation stress and anti-oxidation abilities in astrocytes, and thus might contribute to brain injury. Methods Changes of GSH, MDA, SOD,MAO-B, nitric oxide were measured after AGEs treatment. Results Both 0.1 g/L Glu-BSA and Gal-BSA could slightly decrease GSH level, while 1 g/L of them significantly decreased GSH level by 35% and 43% respectively. The MDA levels of both 1 g/L AGEs treated groups (306±13 and 346±22) were higher than that of the normal group (189±18), which could be inhibited by free radical scavenger NAC. The SOD activities of both 1 g/L AGEs treated groups (67.0±5.2 and 74.0±11.0)were lower than that of the normal group (85.2±8.0). Both 0.1 g/L AGEs could slightly increase the activity of MAO-B, while 1 g/L of them could increase MAO-B activity by 1.5 and 1.7 folds respectively. Both AGEs stimulation could produce NO level by 1.7 and 2 folds respectively.Conclusion Enhanced levels of astrocytic oxidation stress and decrease of antioxidation abilities may contribute to, at least partially, the detrimental effects of AGEs in neuronal disorders and aging brain.

  2. Oxidative Stress and Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases

    Science.gov (United States)

    Chang, Yu-Chun

    2016-01-01

    Aging-associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs. PMID:27807472

  3. Oxidative Stress and Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Cheng-Chieh Chang

    2016-01-01

    Full Text Available Aging-associated cardiovascular diseases (CVDs have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs.

  4. A Precipitate-Strengthening Model Based on Crystallographic Anisotropy, Stress-Induced Orientation, and Dislocation of Stress-Aged Al-Cu-Mg Single Crystals

    Science.gov (United States)

    Guo, Xiaobin; Zhang, Yong; Zhang, Jin; Deng, Yunlai; Zhang, Xinming

    2017-10-01

    We investigate the relationship between inhomogeneously distributed S precipitates and hardness of stress-aged single-crystal Al-Cu-Mg. First, the effect of crystallographic anisotropy is considered and modeled from the results of free-stress aged single-crystal Al-1.2Cu-0.5Mg with ( 1\\bar{1}8 ), ( \\bar{1}\\bar{2}5 ), (356), and (319) plane orientations. Effect of crystallographic anisotropy depends on the angle between the plane orientation of the single crystal and {012} habit planes of the S precipitates. Second, the effects of the magnitude of the applied stress and direction on the S-laths' size and distribution are considered. As the applied stress-induced S-laths inhomogeneously distribute during aging, the effect of the single-crystal's orientation on the distribution of S-laths is modeled. The results show that a single crystal near (111) plane orientation has the lowest stress-orienting effect. Finally, at higher applied stresses, such as 50 MPa, the S precipitates disperse more homogeneously due to the influence of the dislocations. Inhibiting the effect of dislocation depends on the angle between the plane orientation of the single crystal and the {111} dislocation slide planes. A precipitate-strengthening model of the stress-aged Al-Cu-Mg alloys is established based on crystallographic anisotropy, stress-orienting precipitates, and inhibiting the effect of dislocations.

  5. Advanced glycation end products, oxidative stress and metalloproteinases are altered in the cerebral microvasculature during aging.

    Science.gov (United States)

    Safciuc, Florentina; Constantin, Alina; Manea, Adrian; Nicolae, Manuela; Popov, Doina; Raicu, Monica; Alexandru, Dorin; Constantinescu, Elena

    2007-11-01

    Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.

  6. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress.

    Science.gov (United States)

    Morita, Norishige; Sovari, Ali A; Xie, Yuanfang; Fishbein, Michael C; Mandel, William J; Garfinkel, Alan; Lin, Shien-Fong; Chen, Peng-Sheng; Xie, Lai-Hua; Chen, Fuhua; Qu, Zhilin; Weiss, James N; Karagueuzian, Hrayr S

    2009-11-01

    Oxidative stress with hydrogen peroxide (H(2)O(2)) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H(2)O(2) on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3-5 mo, N = 25) and rabbit (3-5 mo, N = 6) hearts exhibited no arrhythmias when perfused with H(2)O(2) (0.1-2 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24-26 mo) rat hearts, 0.1 mM H(2)O(2) caused EAD-mediated TA, leading to ventricular tachycardia (VT) and fibrillation (VF). Aged rabbits (life span, 8-12 yr) were not available, but 4 of 10 middle-aged rabbits (3-5 yr) developed EADs, TA, VT, and VF. These arrhythmias were suppressed by the reducing agent N-acetylcysteine (2 mM) and CaMKII inhibitor KN-93 (1 microM) but not by its inactive form (KN-92, 1 microM). There were no significant differences between action potential duration (APD) or APD restitution slope before or after H(2)O(2) in aged or young adult rat hearts. In histological sections, however, trichrome staining revealed that aged rat hearts exhibited extensive fibrosis, ranging from 10-90%; middle-aged rabbit hearts had less fibrosis (5-35%), whereas young adult rat and rabbit hearts had ventricular base where fibrosis was intermediate ( approximately 30%). Computer simulations in two-dimensional tissue incorporating variable degrees of fibrosis showed that intermediate (but not mild or severe) fibrosis promoted EADs and TA. We conclude that in aged ventricles exposed to oxidative stress, fibrosis facilitates the ability of cellular EADs to emerge and generate TA, VT, and VF at the tissue level.

  7. Aged Stem Cells Reprogram Their Daily Rhythmic Functions to Adapt to Stress.

    Science.gov (United States)

    Solanas, Guiomar; Peixoto, Francisca Oliveira; Perdiguero, Eusebio; Jardí, Mercè; Ruiz-Bonilla, Vanessa; Datta, Debayan; Symeonidi, Aikaterini; Castellanos, Andrés; Welz, Patrick-Simon; Caballero, Juan Martín; Sassone-Corsi, Paolo; Muñoz-Cánoves, Pura; Benitah, Salvador Aznar

    2017-08-10

    Normal homeostatic functions of adult stem cells have rhythmic daily oscillations that are believed to become arrhythmic during aging. Unexpectedly, we find that aged mice remain behaviorally circadian and that their epidermal and muscle stem cells retain a robustly rhythmic core circadian machinery. However, the oscillating transcriptome is extensively reprogrammed in aged stem cells, switching from genes involved in homeostasis to those involved in tissue-specific stresses, such as DNA damage or inefficient autophagy. Importantly, deletion of circadian clock components did not reproduce the hallmarks of this reprogramming, underscoring that rewiring, rather than arrhythmia, is associated with physiological aging. While age-associated rewiring of the oscillatory diurnal transcriptome is not recapitulated by a high-fat diet in young adult mice, it is significantly prevented by long-term caloric restriction in aged mice. Thus, stem cells rewire their diurnal timed functions to adapt to metabolic cues and to tissue-specific age-related traits. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The effect of technical replicate (repeats) on Nix Pro Color Sensor™ measurement precision for meat: A case-study on aged beef colour stability.

    Science.gov (United States)

    Holman, Benjamin W B; Collins, Damian; Kilgannon, Ashleigh K; Hopkins, David L

    2017-09-04

    The Nix Pro Colour Sensor™ (NIX) can be potentially used to measure meat colour, but procedural guidelines that assure measurement reproducibility and repeatability (precision) must first be established. Technical replicate number (r) will minimise response variation, measureable as standard error of predicted mean (SEM), and contribute to improved precision. Consequently, we aimed to explore the effects of r on NIX precision when measuring aged beef colour (colorimetrics; L*, a*, b*, hue and chroma values). Each colorimetric SEM declined with increasing r to indicate improved precision and followed a diminishing rate of improvement that allowed us to recommend r=7 for meat colour studies using the NIX. This definition was based on practical limitations and a* variability, as additional r would be required if other colorimetrics or advanced levels of precision are necessary. Beef ageing and display period, holding temperature, loin and sampled portion were also found to contribute to colorimetric variation, but were incorporated within our definition of r. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  9. Stress as a major determinant of migraine in women aged 25-65 years

    Directory of Open Access Journals (Sweden)

    Woro Riyadina

    2014-08-01

    Full Text Available Background Migraine is a primary headache causing substantial disability in patients. The prevalence of migraine in women is still high. Menarche, menstruation, pregnancy, menopause, and the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. The aim of this study was to determine the major determinants of migraine in adult women aged 25-65 years. Methods A cross-sectional study of 2,747 women from the baseline study “Cohort Study of Risk Factors for Non-Communicable Diseases”. The dependent variable was migraine based on the diagnosis of health providers or symptoms. Independent variables were demographic (age, marital status, education and behavioral (smoking, diet, and stress characteristics, metabolic disorders (obesity, hypertension, dyslipidemia, and hormonal factors (contraception and hormone therapy. Data were collected through interviews (characteristics, health and hormonal status, diet, measurement (anthropometrics, blood pressure, and health examination (blood specimens, neurology. Data were analyzed by chi-square test and multiple logistic regression. Results Migraine in adult women was found in 710 cases (25.8% with symptoms of worsening with activity (15%, nausea and vomiting (13%, and photophobia/phonophobia (4.1%. The main determinant of migraine in adult women was stress with a 2.47-fold risk [95% CI = 2.07 to 2.95] as compared with no stress, after controlling for smoking, menstruation and hormonal drug consumption. Conclusion Stress is a major determinant of migraine in adult women, therefore health programs should be instituted through health promotion, prevention and education to control stress.

  10. Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.

    Science.gov (United States)

    Qiu, Zhi-Kun; Zhang, Li-Ming; Zhao, Nan; Chen, Hong-Xia; Zhang, You-Zhi; Liu, Yan-Qin; Mi, Tian-Yue; Zhou, Wen-Wen; Li, Yang; Yang, Ri-Fang; Xu, Jiang-Ping; Li, Yun-Feng

    2013-08-01

    Post-traumatic stress disorder (PTSD) is a severely disabling anxiety disorder that may occur following exposure to a serious traumatic event. It is a psychiatric condition that can afflict anyone who has experienced a life-threatening or violent event. Previous studies have shown that changes in 18 kDa translocator protein (TSPO) expression (or function), a promising target for treating neurological disorders without benzodiazepine-like side effects, may correlate with PTSD. However, few studies have investigated the anti-PTSD effects of TSPO ligands. AC-5216, a ligand for TSPO, induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether AC-5216 ameliorates PTSD behavior in mice. Following the training session consisting of exposure to inescapable electric foot shocks, animals were administered AC-5216 daily during the behavioral assessments, i.e., situational reminders (SRs), the open field (OF) test, the elevated plus-maze (EPM) test, and the staircase test (ST). The results indicated that exposure to foot shocks induced long-term behavioral deficiencies in the mice, including freezing and anxiety-like behavior, which were significantly ameliorated by repeated treatment with AC-5216 but without any effect on spontaneous locomotor activity or body weight. In summary, this study demonstrated the anti-PTSD effects of AC-5216 treatment, suggesting that TSPO may represent a therapeutic target for anti-PTSD drug discovery and that TSPO ligands may be a promising new class of drugs for the future treatment of PTSD.

  11. Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Cuzzocrea, Salvatore; Iavicoli, Ivo; Rizzarelli, Enrico; Calabrese, Edward J

    2011-08-01

    Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by co-ordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, such as carnosine, carnitines or polyphenols, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose-response, challenges long-standing beliefs about the nature of the dose-response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. In this review we discuss the most current and up to date

  12. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.

    Science.gov (United States)

    García-Mesa, Yoelvis; Colie, Sandra; Corpas, Rubén; Cristòfol, Rosa; Comellas, Francesc; Nebreda, Angel R; Giménez-Llort, Lydia; Sanfeliu, Coral

    2016-01-01

    Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.

  13. Morphological evidence for a change in the pattern of aortic wall shear stress with age.

    Science.gov (United States)

    Bond, Andrew R; Iftikhar, Saadia; Bharath, Anil A; Weinberg, Peter D

    2011-03-01

    The distribution of atherosclerosis around branch sites changes with age in human and rabbit aortas. We tested whether that reflects a change in the pattern of wall shear stress by examining shear-dependent morphological features of endothelial cells. Endothelial cells and their nuclei align and elongate with applied shear. These parameters were examined in the descending thoracic aorta of immature and mature rabbits. The use of Häutchen preparations, fluorescent stains, and automated image analysis allowed nuclear morphology to be mapped reliably at high resolution over large areas. Cells and their nuclei were most elongated downstream of branch ostia in immature aortas but upstream of them in mature aortas. Elongation was generally greater in mature animals, and nuclei aligned toward the ostia more in these animals, consistent with a greater flow into the branch. Morphology away from branches was indicative of helical flow in the aorta, with greatest shear on the dorsal wall, at both ages. The data are consistent with age-related changes in the pattern of shear around aortic branches. Maps of nuclear elongation closely resembled maps of lesion frequency. The association was positive, implying that lesions occur at sites of high shear stress at both ages.

  14. Neocortex and allocortex respond differentially to cellular stress in vitro and aging in vivo.

    Directory of Open Access Journals (Sweden)

    Jessica M Posimo

    Full Text Available In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more vulnerable to low concentrations of the proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The proteasome appeared to be more impaired in allocortex because MG132 raised ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase. Proteasome subunits PA700 and PA28 were also higher in allocortex cultures, suggesting compensatory adaptations to greater proteasome impairment. Glutathione and ceruloplasmin were not robustly MG132-responsive and were basally higher in neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132 as allocortex when glutathione synthesis or autophagic defenses were inhibited. Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex resilient to MG132. Glutathione and ceruloplasmin levels were then examined in vivo as a function of age because aging is a natural model of proteasome inhibition and oxidative stress. Allocortical glutathione levels rose linearly with age but were similar to neocortex in whole tissue lysates. In contrast, ceruloplasmin levels were strikingly higher in neocortex at all ages and rose linearly until middle age. PA28 levels rose with age and were higher in allocortex in vivo, also paralleling in vitro data. These neo- and allocortical differences have implications for the many studies that treat the telencephalic mantle as a single unit. Our observations suggest that the topographic progression of protein

  15. Neocortex and allocortex respond differentially to cellular stress in vitro and aging in vivo.

    Science.gov (United States)

    Posimo, Jessica M; Titler, Amanda M; Choi, Hailey J H; Unnithan, Ajay S; Leak, Rehana K

    2013-01-01

    In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more vulnerable to low concentrations of the proteasome inhibitors MG132 and PSI but not the oxidative poison H2O2. The proteasome appeared to be more impaired in allocortex because MG132 raised ubiquitin-conjugated proteins and lowered proteasome activity in allocortex more than neocortex. Allocortex cultures were more vulnerable to MG132 despite greater MG132-induced rises in heat shock protein 70, heme oxygenase 1, and catalase. Proteasome subunits PA700 and PA28 were also higher in allocortex cultures, suggesting compensatory adaptations to greater proteasome impairment. Glutathione and ceruloplasmin were not robustly MG132-responsive and were basally higher in neocortical cultures. Notably, neocortex cultures became as vulnerable to MG132 as allocortex when glutathione synthesis or autophagic defenses were inhibited. Conversely, the glutathione precursor N-acetyl cysteine rendered allocortex resilient to MG132. Glutathione and ceruloplasmin levels were then examined in vivo as a function of age because aging is a natural model of proteasome inhibition and oxidative stress. Allocortical glutathione levels rose linearly with age but were similar to neocortex in whole tissue lysates. In contrast, ceruloplasmin levels were strikingly higher in neocortex at all ages and rose linearly until middle age. PA28 levels rose with age and were higher in allocortex in vivo, also paralleling in vitro data. These neo- and allocortical differences have implications for the many studies that treat the telencephalic mantle as a single unit. Our observations suggest that the topographic progression of protein aggregations through the

  16. Effect of Pre-aging on Stress Corrosion Cracking of Spray-formed 7075 Alloy in Retrogression and Re-aging

    Science.gov (United States)

    Su, Rui-ming; Qu, Ying-dong; You, Jun-hua; de Li, Rong-

    2015-11-01

    The effects of pre-aging in retrogression and re-aging (RRA) treatment on microstructure, mechanical properties, and stress corrosion cracking (SCC) behavior of spray-formed 7075 aluminum alloy were investigated by tensile test, slow strain rate test, and transmission electron microscope. The results show that the under aging (120 °C for 16 h) as the pre-aging in RRA treatment can vastly improve the mechanical properties and the SCC resistance of the alloy, compared with early aging (120 °C for 8 h), peak aging (120 °C for 24 h), and over aging (120 °C for 32 h) treatments, the ultimate tensile strength of the alloy is 782 MPa, which is higher than that for peak aging or conventional RRA treatment; and the SCC resistance of the alloy is also excellent after RRA with under aging as pre-aging.

  17. Amla (Emblica officinalis Gaertn.) attenuates age-related renal dysfunction by oxidative stress.

    Science.gov (United States)

    Yokozawa, Takako; Kim, Hyun Young; Kim, Hyun Ju; Tanaka, Takashi; Sugino, Hidetoshi; Okubo, Tsutomu; Chu, Djong-Chi; Juneja, Lekh Raj

    2007-09-19

    To investigate the effects of amla on renal dysfunction involved in oxidative stress during the aging process, we employed young (2 months old) and aged (13 months old) male rats and administered SunAmla (Taiyo Kagaku Co., Ltd., Japan) or an ethyl acetate (EtOAc) extract of amla, a polyphenol-rich fraction, at a dose of 40 or 10 mg/kg body weight/day for 100 days. The administration of SunAmla or EtOAc extract of amla reduced the elevated levels of serum creatinine and urea nitrogen in the aged rats. In addition, the tail arterial blood pressure was markedly elevated in aged control rats as compared with young rats, while the systolic blood pressure was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Furthermore, the oral administration of SunAmla or EtOAc extract of amla significantly reduced thiobarbituric acid-reactive substance levels of serum, renal homogenate, and mitochondria in aged rats, suggesting that amla would ameliorate oxidative stress under aging. The increases of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in the aorta of aging rats were also significantly suppressed by SunAmla extract or EtOAc extract of amla, respectively. Moreover, the elevated expression level of bax, a proapoptotic protein, was significantly decreased after oral administration of SunAmla or EtOAc extract of amla. However, the level of bcl-2, an antiapoptotic protein, did not show any difference among the groups. The expressions of renal nuclear factor-kappaB (NF-kappaB), inhibitory kappaB in cytoplasm, iNOS, and COX-2 protein levels were also increased with aging. However, SunAmla or EtOAc extract of amla reduced the iNOS and COX-2 expression levels by inhibiting NF-kappaB activation in the aged rats. These results indicate that amla would be a very useful antioxidant for the prevention of age-related renal disease.

  18. Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis.

    Science.gov (United States)

    Yang, Jiancheng; Zong, Xiaomeng; Wu, Gaofeng; Lin, Shumei; Feng, Ying; Hu, Jianmin

    2015-08-01

    In males, the decline of androgen synthesis, spermatogenesis and sexual function are the main phenotypes of aging, which may be attributed to testicular dysfunction. Taurine can act as an antioxidant, a testosterone secretion stimulator, a sperm membrane stabilizer and motility factor, and an anti-apoptotic agent. Recent observational studies suggested that taurine may play an important role in spermatogenesis, but to date whether taurine has anti-aging effects on testes remains unknown. We found that in aged rats testicular SDH and G6PDH activities, marker enzymes of testes, serum testosterone, testicular 3β-HSD and 17β-HSD mRNA expression levels were significantly increased by taurine treatment. Taurine administration also markedly raised the sperm count, viability and motility, decreased the sperm abnormality. Our data suggested that taurine can postpone testicular function deterioration in aged rats. Importantly, we observed obvious elevation of testicular antioxidant enzymes (SOD, GSH, GSH-Px) activities, and remarkable reduction of ROS and MDA by taurine administration, indicating taurine can decrease testicular oxidative stress and lipid peroxidation in aged rats. Finally, we found taurine effectively reduced testicular DNA fragmentation, increased testicular Bcl-2 protein expression, and decreased cytochrome c, Bax, Fas, FasL and caspase-3 expression, suggesting taurine can prohibit aged testicular apoptosis by mitochondrial dependent and independent signal pathway. In summary, our results indicated that taurine can suppress testicular function deterioration by increasing antioxidant ability and inhibiting apoptosis.

  19. Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

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    Daniëlle M. P. H. J. Boesten

    2013-01-01

    Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

  20. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

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    Janusz Blasiak

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE, Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  1. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration.

    Science.gov (United States)

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  2. CDC Vital Signs: Preventing Repeat Teen Births

    Science.gov (United States)

    ... file Error processing SSI file Preventing Repeat Teen Births Recommend on Facebook Tweet Share Compartir On this ... Too many teens, ages 15–19, have repeat births. Nearly 1 in 5 births to teens, ages ...

  3. The moderating effects of aging and cognitive abilities on the association between work stress and negative affect.

    Science.gov (United States)

    Hyun, Jinshil; Sliwinski, Martin J; Almeida, David M; Smyth, Joshua M; Scott, Stacey B

    2017-03-29

    Given that the association between work stress and negative affect can exacerbate negative health and workplace outcomes, it is important to identify the protective and risk factors that moderate this association. Socioemotional aging and cognitive abilities might influence how people utilize emotion regulation skills and engage in practical problem solving to manage their work stress. The aim of this study is to examine whether age and cognitive abilities independently and interactively moderate the association between work-related stress and negative affect. A diverse working adult sample (N = 139, age 25-65, 69% of females) completed a cross-sectional survey that assessed chronic work stress, negative affect, and fluid and crystallized cognitive abilities. Results from regression analyses suggested that both fluid and crystallized cognitive abilities, but not age, moderated the association between work stress and negative affect. Further, we found that crystallized cognition had a stronger attenuating effect on the work stress-negative affect association for older compared to younger workers. The moderating effect of fluid cognition was invariant across age. Our findings demonstrate that cognitive abilities are an important personal resource that might protect individuals against the negative impacts of work stress and negative affect. Although the role that fluid cognition plays in work stress-negative affect association is comparably important for both younger and older workers, crystallized cognition might play a more valuable role for older than younger workers.

  4. Anxiolytic effects of the GABA(A) receptor partial agonist, L-838,417: impact of age, test context familiarity, and stress.

    Science.gov (United States)

    Morales, Melissa; Varlinskaya, Elena I; Spear, Linda P

    2013-08-01

    The partial α2,3,5 GABA(A) receptor agonist, L-838,417 has been reported to have anxiolytic effects in adult rodents. Although maturational differences exist for the GABA(A) receptor subunits, the anxiolytic effects of L-838,417 have not been tested in younger animals. The goal of the present experiments was to determine whether L-838,417 reverses anxiety-like behavior induced by either an unfamiliar environment (Experiment 1) or repeated restraint stress (Experiment 2) differentially in adolescent and adult, male and female Sprague-Dawley rats using a modified social interaction test. In Experiment 1, rats were injected with 0, 0.5, 1.0, 2.0, or 4.0 mg/kg L-838,417, i.p. and tested 30 min later in an unfamiliar test context for 10 min. In Experiment 2, rats were exposed to restraint stress (90 min daily for 5 days). Immediately after the last restraint session, animals were injected with L-838,417 and placed alone for 30 min in the test apparatus to familiarize them to this context prior to the 10 min social interaction test. In Experiment 1, L-838,417 produced anxiolytic effects in adults at 1.0 mg/kg, as indexed by a transformation of social avoidance into preference and an increase in social investigation. In adolescents, a dose of 2.0 mg/kg eliminated social avoidance, but had no anxiolytic effects on social investigation. Testing under familiar circumstances (Experiment 2) after repeated restraint stress eliminated age differences in sensitivity to L-838,417, with 0.5 mg/kg reversing the anxiogenic effects of prior stress regardless of age, but with doses ≥ 1 mg/kg decreasing social investigation, an effect possibly due in part to locomotor-impairing effects of this compound. Although locomotor activity was suppressed in both experiments, higher doses of L-838,417 were necessary to suppress locomotor activity in Experiment 1. Thus, anxiolytic effects of L-838,417 were found to be context-, age-, and stress-dependent.

  5. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

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    Tamara Simpson

    2015-01-01

    Full Text Available The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function.

  6. Lithium-ion battery aging mechanisms and life model under different charging stresses

    Science.gov (United States)

    Gao, Yang; Jiang, Jiuchun; Zhang, Caiping; Zhang, Weige; Ma, Zeyu; Jiang, Yan

    2017-07-01

    The charging time-consuming and lifespan of lithium-ion batteries have always been the bottleneck for the tremendous application of electric vehicles. In this paper, cycle life tests are conducted to reveal the influence of different charging current rates and cut-off voltages on the aging mechanism of batteries. The long-term effects of charging current rates and cut-off voltages on capacity degradation and resistance increase are compared. The results show that there exists a critical charging current and a critical charging cut-off voltage. When the charging stress exceeds the critical value, battery degradation speed will be greatly accelerated. Furthermore, battery aging mechanisms at various charging currents and cut-off voltages are investigated using incremental capacity analysis. It is indicated that charging current and cut-off voltage should be reduced to retard battery degradation when the battery degrades to a certain extent. The time when the loss of electrode material accelerates is taken as the crisis to reduce charging current and the time when the loss of lithium inventory accelerates is taken as the crisis to reduce charging cut-off voltage. Moreover, an experiential model quantitatively describing the relationship between capacity degradation rate and charging stresses at different aging states is established.

  7. Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol.

    Science.gov (United States)

    Rajapakse, Angana G; Yepuri, Gautham; Carvas, João M; Stein, Sokrates; Matter, Christian M; Scerri, Isabelle; Ruffieux, Jean; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2011-04-22

    Mammalian target of rapamycin (mTOR)/S6K1 signalling emerges as a critical regulator of aging. Yet, a role of mTOR/S6K1 in aging-associated vascular endothelial dysfunction remains unknown. In this study, we investigated the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells. We show here that senescent endothelial cells displayed higher S6K1 activity, increased superoxide production and decreased bioactive nitric oxide (NO) levels than young endothelial cells, which is contributed by eNOS uncoupling. Silencing S6K1 in senescent cells reduced superoxide generation and enhanced NO production. Conversely, over-expression of a constitutively active S6K1 mutant in young endothelial cells mimicked endothelial dysfunction of the senescent cells through eNOS uncoupling and induced premature cellular senescence. Like the mTOR/S6K1 inhibitor rapamycin, resveratrol inhibited S6K1 signalling, resulting in decreased superoxide generation and enhanced NO levels in the senescent cells. Consistent with the data from cultured cells, an enhanced S6K1 activity, increased superoxide generation, and decreased bioactive NO levels associated with eNOS uncoupling were also detected in aortas of old WKY rats (aged 20-24 months) as compared to the young animals (1-3 months). Treatment of aortas of old rats with resveratrol or rapamycin inhibited S6K1 activity, oxidative stress, and improved endothelial NO production. Our data demonstrate a causal role of the hyperactive S6K1 in eNOS uncoupling leading to endothelial dysfunction and vascular aging. Resveratrol improves endothelial function in aging, at least in part, through inhibition of S6K1. Targeting S6K1 may thus represent a novel therapeutic approach for aging-associated vascular disease.

  8. Age-related changes in rat testicular oxidative stress parameters by hexachlorocyclohexane

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, L.; Sahoo, A.; Chainy, G.B.N. [Biochemistry Unit, Department of Zoology, Utkal University, Bhubaneswar (India)

    1999-03-01

    Effect of repeated oral administration of hexachlorocyclohexane (HCH; 10 and 20 mg/kg body weight per day for 7, 15 and 30 days) on antioxidant defence system and lipid peroxidation (LPX) in the testis was compared between immature (15-day-old) and mature (90-day-old) rats. In both age-groups of rats, the pesticide elicited a significant decrease in the activities of cytosolic superoxide dismutase (SOD; total and CN{sup -}-resistant) and catalase, and ascorbic acid content together with an increase in the levels of LPX (both in crude homogenate and subcellular fractions) and H{sub 2}O{sub 2}. Testicular glutathione peroxidase (GPx; total and non-selenium-dependent) activity was enhanced in both the age-groups of rats while the testicular glutathione content as well as glutathione reductase activity remained unaltered. HCH treatment resulted in a decrease of total epididymal sperm number with a higher incidence of dead and damaged spermatozoa, and sperms having anomalous head. Statistical analyses suggest that the alterations in the testicular antioxidant defence profile in the rat are not only dependent on the duration of pesticide treatment, but also influenced by age. (orig.) With 6 figs., 3 tabs., 45 refs.

  9. Prediction of residual stress due to early age behaviour of massive concrete structures: on site experiments and macroscopic modelling

    CERN Document Server

    Zreiki, Jihad; Chaouche, Mohend; Moranville, Micheline

    2008-01-01

    Early age behaviour of concrete is based on complex multi-physical and multiscale phenomena. The predication of both cracking risk and residual stresses in hardened concrete structures is still a challenging task. We propose in this paper a practical method to characterize in the construction site the material parameters and to identify a macroscopic model from simple tests. We propose for instance to use a restrained shrinkage ring test to identify a basic early age creep model based on a simple ageing visco-elastic Kelvin model. The strain data obtained from this test can be treated through an early age finite element incremental procedure such that the fitting parameters of the creep law can be quickly identified. The others properties of concrete have been measured at different ages (elastic properties, hydration kinetics, and coefficient of thermal expansion). From the identified early age model, we computed the temperature rise and the stress development in a non reinforced concrete stress for nuclear w...

  10. Blood pressure and heart rate during stress in children born small for gestational age.

    Science.gov (United States)

    Pirojsakul, Kwanchai; Thanapinyo, Apinya; Nuntnarumit, Pracha

    2017-06-01

    Increased sympathetic nervous system activity has been proposed as a potential mechanism for the blood pressure (BP) elevation seen in individuals born small for gestational age (SGA). This study was carried out to detect the changes in BP and heart rate (HR) in children born SGA during exposure to stress and to assess for changes in urinary catecholamine excretion. Nineteen children aged 6-14 years born SGA and 17 age- and gender-matched healthy controls were included in the study. The stress test included a mathematical test and venipuncture. BP and HR were monitored during the test. Spot urine samples were collected at baseline and after the stress test to determine dopamine, epinephrine and norepinephrine levels. At baseline, there was no difference in BP and HR between the SGA and control groups, but mean urinary norepinephrine levels were slightly higher in the SGA group (55.7 ± 16.1 vs. 43.4 ± 3.8 mcg/gCr; P = 0.10). Compared to the control group, mean maximal HR increase was higher in the SGA group (31.3 ± 3.1 vs. 19.2 ± 3.8%; P = 0.008), and mean duration of maximal HR to baseline HR was longer (186 ± 23 vs. 97 ± 13 s, respectively; P = 0.003). There was a significant negative correlation between birth weight and maximal HR increase (r = -0.497, P = 0.003). Children born SGA showed significantly greater increases in HR and significantly longer periods of tachycardia during exposure to stress than did healthy controls. The rise in HR was inversely correlated with birth weight. These findings suggest that children born SGA have a greater increase in sympathetic response when exposed to stress than do healthy individuals.

  11. Inflammation and Oxidative Stress in Young and Aged Rats after Acute Homocysteine Administration

    Directory of Open Access Journals (Sweden)

    Cristina-Sorina CĂTANĂ

    2011-06-01

    Full Text Available Introduction: Hyperhomocysteinemia plays an etiologic role in homocystinuria, neurodegenerative and cardiovascular diseases. Potential mechanisms involved in the degenerative diseases of aging include: oxidative stress, endothelial dysfunction and inflammation. Aim: In the present study we evaluated the effect of acute administration of homocysteine (Hcy, at a level similar to that found in homocystinuria, on biochemical markers of inflammation (such as IL-6 and of oxidative stress (such as gluthathione peroxidase - GPx. Material and Method: The study was performed on 40 young and older Wistar rats. IL-6 serum level was quantified by a high-sensitivity enzyme-linked immunoabsorbent assay (ELISA method and the activity of whole blood GPx was measured using a commercially available Randox kit. Results: Our results showed that Hcy administration increased the pro-inflammatory cytokine IL-6 in young rats (p<0.3 and decreased IL-6 level in older rats (p<0.008, when compared to the control group. GPx activity was found to increase with age (587.07 U/gHb versus 847.5 U/gHb, p<0.001. Two hours after Hcy administration, GPx activity was found to decrease, but not in a statistically significant manner. The difference between GPx activities in Hcy treated groups remains statistically significant (p<0.01 in the younger group, compared to older group (556.62 U/gHb versus 748.38 U/gHb. Conclusion: Our results indicate the existence of a correlation between hyperhomocysteinemia, proinflammatory state and oxidative stress, illustrated by the direct dependence of whole blood GPx activities on the increasing age.

  12. Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels.

    Science.gov (United States)

    Wu, Wanqiang; Wang, Xin; Xiang, Qisen; Meng, Xu; Peng, Ye; Du, Na; Liu, Zhigang; Sun, Quancai; Wang, Chan; Liu, Xuebo

    2014-01-01

    Astaxanthin (AST) is a carotenoid pigment which possesses potent antioxidative, anti-inflammatory, and neuroprotective properties. The aim of this study was to investigate whether administration of AST had protective effects on D-galactose-induced brain aging in rats, and further examined its protective mechanisms. The results showed that AST treatment significantly restored the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and increased glutathione (GSH) contents and total antioxidant capacity (T-AOC), but decreased malondialdehyde (MDA), protein carbonylation and 8-hydroxy-2- deoxyguanosine (8-OHdG) levels in the brains of aging rats. Furthermore, AST increased the ratio of Bcl-2/Bax, but decreased the expression of Cyclooxygenase-2 (COX-2) in the brains of aging rats. Additionally, AST ameliorated histopathological changes in the hippocampus and restored brain derived neurotrophic factor (BDNF) levels in both the brains and hippocampus of aging rats. These results suggested that AST could alleviate brain aging, which may be due to attenuating oxidative stress, ameliorating hippocampus damage, and upregulating BDNF expression.

  13. Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats.

    Directory of Open Access Journals (Sweden)

    Lorena Fernandes Arruda

    Full Text Available Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2 and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2 relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging.

  14. Effect of ageing and oxidative stress on antioxidant enzyme activity in different regions of the rat kidney.

    Science.gov (United States)

    Thiab, Noor Riyadh; King, Nicola; Jones, Graham L

    2015-10-01

    Oxidative stress has been implicated in ageing and the pathogenesis of chronic kidney disease. We examined levels of antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and superoxide dismutase as modulated by age and oxidative stress in different regions of the kidney. Antioxidant enzymes were examined in different regions of the kidney in male Wistar rats. Kidneys from rats of different ages (5, 12, 36 and 60 weeks) were dissected into cortex, outer medulla and inner medulla. Tissues were incubated for 30 min with or without 0.2 mM H2O2 to induce oxidative stress. Antioxidant enzyme activities progressively decreased with age under both control and stress conditions (P Antioxidant enzyme activities were greater in the cortex (P < 0.05) by comparison with the outer and inner medulla, respectively.

  15. Some remarks on the influence of temperature-variations, non-linearities, repeatability and ageing on modal-analysis for structural health monitoring of real bridges

    Directory of Open Access Journals (Sweden)

    Maas Stefan

    2015-01-01

    Full Text Available Structural Health Monitoring (SHM intends to identify damage by changes of characteristics as for instance the modal parameters. The eigenfrequencies, mode-shapes and damping-values are either directly used as damage indicators or the changes of derived parameters are analysed, such as e.g. flexibilities or updated finite element models. One common way is a continuous monitoring under environmental excitation forces, such as wind or traffic, i.e. the so-called output-only modal analysis. Alternatively, a forced measured external excitation in distinct time-intervals may be used for input-output modal analysis. Both methods are limited by the precision or the repeatability under real-life conditions at site. The paper will summarize several field tests of artificially step-by-step damaged bridges prior to their final demolishment and it will show the changes of eigenfrequencies due to induced artificial damage. Additionally, some results of a monitoring campaign of a healthy bridge in Luxembourg are presented. Reinforced concrete shows non-linear behaviour in the sense that modal parameters depend on the excitation force amplitude, i.e. higher forces lead often to lower eigenfrequencies than smaller forces. Furthermore, the temperature of real bridges is neither constant in space nor in time, while for instance the stiffness of asphalt is strongly dependant on it. Finally, ageing as such can also change a bridge’s stiffness and its modal parameters, e.g. because creep and shrinkage of concrete or ageing of elastomeric bearing pads influence their modulus of elasticity. These effects cannot be considered as damage, though they influence the measurement of modal parameters and hinder damage detection.

  16. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  17. Association between repeated unpredictable chronic mild stress (UCMS procedures with a high fat diet: a model of fluoxetine resistance in mice.

    Directory of Open Access Journals (Sweden)

    Elsa Isingrini

    Full Text Available Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS. Male BALB/c mice were given either a regular (4% fat or a high fat diet (45% fat and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p. was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight and behavioural tests (the reward maze test and the splash test. The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test and anhedonia (reward maze test and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS-an already validated animal model of depression-with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression.

  18. Association between Repeated Unpredictable Chronic Mild Stress (UCMS) Procedures with a High Fat Diet: A Model of Fluoxetine Resistance in Mice

    Science.gov (United States)

    Isingrini, Elsa; Camus, Vincent; Le Guisquet, Anne-Marie; Pingaud, Maryse; Devers, Séverine; Belzung, Catherine

    2010-01-01

    Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs) has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS). Male BALB/c mice were given either a regular (4% fat) or a high fat diet (45% fat) and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p.) was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight) and behavioural tests (the reward maze test and the splash test). The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test) and anhedonia (reward maze test) and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS—an already validated animal model of depression—with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression. PMID:20436931

  19. Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: effects of pre- and post-ageing administration.

    Science.gov (United States)

    Safwat, M H; El-Sawalhi, M M; Mausouf, M N; Shaheen, A A

    2014-05-01

    The ageing process is known to be accompanied by increased oxidative stress and compromised antioxidant defenses. Controlled ozone administration has been shown to be effective in various pathophysiological conditions with an underlying oxidative burden. However, its effect on the biochemical alterations associated with the ageing process has been rarely studied. Therefore, the present work was carried out to study the role of ozone in counteracting the state of oxidative stress associated with ageing in rat liver and kidneys using two experimental models. In the pre-ageing model, ozone was administered prior to the onset of ageing at adulthood and continued after the start of the ageing process (3-month-old rats until the age of 15 months). While in the post-ageing model, ozone was administered after ageing has begun and lasted for one month (14-month-old rats until the age of 15 months). The pre-ageing ozone administration effectively reduced lipid and protein oxidation markers, namely, malondialdehyde and protein carbonyl levels and decreased lipofuscin pigment deposition in rat liver and kidneys. Moreover, it significantly restored hepatic and renal reduced glutathione (GSH) contents and normalized cytosolic hepatic glutathione peroxidase activity. Similar but less pronounced effects were observed in the post-ageing ozone-treated group. Nevertheless, in the latter model ozone administration failed to significantly affect liver and kidney lipofuscin levels, as well as kidney GSH contents. These data provide evidences for potentially positive effects of pre-ageing ozone therapy in neutralizing chronic oxidative stress associated with ageing in rat liver and kidneys.

  20. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

    Science.gov (United States)

    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  1. Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

    Directory of Open Access Journals (Sweden)

    Petra Maria Hermann

    2014-12-01

    Full Text Available TThe aging brain can undergo a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (peroxidation of membrane lipids and activation of phospholipase A2 (PLA2 enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the Biology of cognitive aging we (1 portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and (2 recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

  2. Polymer Prize Talk: Segmental Dynamics in Polymers : From Cold Melts to Aging and Stressed Glasses

    Science.gov (United States)

    Schweizer, Kenneth

    2008-03-01

    Polymers are excellent glass formers. In the cold molten state they exhibit chemically-specific and strongly non-Arrenhius segmental relaxation which sets the time scale for the generic chain scale dynamics. In the amorphous solid or plastic state the temperature dependence of the alpha relaxation time changes, physical aging emerges, and a rich mechanical response occurs characterized by the dynamic yielding, strain softening and strain hardening processes. We have developed a statistical mechanical theory of activated segmental relaxation in cold melts by combining and extending methods of mode coupling, dynamic density functional and activated hopping theories. The approach is built on the concept of a confining nonequilibrium free energy which quantifies local dynamical constraints and the barrier hopping process. The localizing consequences of interchain caging forces are quantified by the amplitude of nanometer scale density fluctuations (compressibility) and backbone stiffness. Predictions for the kinetic glass and dynamic crossover temperatures, dynamic fragility, and thermal dependence of the segmental relaxation time are consistent with experiments. The theory has been generalized to treat alpha relaxation, physical aging, and nonlinear mechanical properties in the glass. The structural component of density fluctuations become (partially) frozen resulting in a crossover to Arrenhius relaxation. Physical aging is modeled based on a kinetic equation for collective density fluctuations. At intermediate time scales the relaxation time (shear modulus) grows as a power law (logarithmic) function of aging time with a temperature dependent exponent. Applied stress weakens dynamical constraints thereby accelerating relaxation and softening the elastic modulus. A constitutive equation has been constructed from which the temperature dependent dynamic yielding and mechanical response under constant strain rate, constant stress (creep), and other modes of deformation

  3. Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection.

    Science.gov (United States)

    Pamplona, Reinald; Barja, Gustavo

    2006-01-01

    Caloric restriction (CR) decreases aging rate and mitochondrial ROS (MitROS) production and oxidative stress in rat postmitotic tissues. Low levels of these parameters are also typical traits of long-lived mammals and birds. However, it is not known what dietary components are responsible for these changes during CR. It was recently observed that 40% protein restriction without strong CR also decreases MitROS generation and oxidative stress. This is interesting because protein restriction also increases maximum longevity (although to a lower extent than CR) and is a much more practicable intervention for humans than CR. Moreover, it was recently found that 80% methionine restriction substituting it for l-glutamate in the diet also decreases MitROS generation in rat liver. Thus, methionine restriction seems to be responsible for the decrease in ROS production observed in caloric restriction. This is interesting because it is known that exactly that procedure of methionine restriction also increases maximum longevity. Moreover, recent data show that methionine levels in tissue proteins negatively correlate with maximum longevity in mammals and birds. All these suggest that lowering of methionine levels is involved in the control of mitochondrial oxidative stress and vertebrate longevity by at least two different mechanisms: decreasing the sensitivity of proteins to oxidative damage, and lowering of the rate of ROS generation at mitochondria.

  4. Coping with stress during aging: the importance of a resilient brain.

    Science.gov (United States)

    Sampedro-Piquero, P; Álvarez-Suárez, P; Begega, A

    2017-09-15

    Resilience is the ability to achieve a positive outcome when we are in the face of adversity. It supposes an active resistance to adversity by coping mechanisms in which genetic, molecular, neural and environmental factors are involved. Resilience has been usually studied in early ages and few is known about it during aging. In this review, we will address the age-related changes in the brain mechanisms involved in regulating the stress response. Furthermore, using the EE paradigm, we analyse the resilient potential of this intervention and its neurobiological basis. In this case, we will focus on identifying the characteristics of a resilient brain (modifications in HPA structure and function, neurogenesis, specific neuron types, glia, neurotrophic factors, nitric oxide synthase or microRNAs, among others). The evidence suggests that a healthy lifestyle has a crucial role to promote a resilient brain during aging. Along with the behavioral changes described, a better regulation of HPA axis, enhanced levels of postmitotic type-3 cells or changes in GABAergic neurotransmission are some of the brain mechanisms involved in resilience. Future research should identify different biomarkers that increase the resistance to develop mood disorders and based on this knowledge, develop new potential therapeutic targets. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. [The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

    Science.gov (United States)

    Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

    2014-12-15

    The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

  6. Acute post-traumatic stress symptoms and age predict outcome in military blast concussion.

    Science.gov (United States)

    Mac Donald, Christine L; Adam, Octavian R; Johnson, Ann M; Nelson, Elliot C; Werner, Nicole J; Rivet, Dennis J; Brody, David L

    2015-05-01

    High rates of adverse outcomes have been reported following blast-related concussive traumatic brain injury in US military personnel, but the extent to which such adverse outcomes can be predicted acutely after injury is unknown. We performed a prospective, observational study of US military personnel with blast-related concussive traumatic brain injury (n = 38) and controls (n = 34) enrolled between March and September 2012. Importantly all subjects returned to duty and did not require evacuation. Subjects were evaluated acutely 0-7 days after injury at two sites in Afghanistan and again 6-12 months later in the United States. Acute assessments revealed heightened post-concussive, post-traumatic stress, and depressive symptoms along with worse cognitive performance in subjects with traumatic brain injury. At 6-12 months follow-up, 63% of subjects with traumatic brain injury and 20% of controls had moderate overall disability. Subjects with traumatic brain injury showed more severe neurobehavioural, post-traumatic stress and depression symptoms along with more frequent cognitive performance deficits and more substantial headache impairment than control subjects. Logistic regression modelling using only acute measures identified that a diagnosis of traumatic brain injury, older age, and more severe post-traumatic stress symptoms provided a good prediction of later adverse global outcomes (area under the receiver-operating characteristic curve = 0.84). Thus, US military personnel with concussive blast-related traumatic brain injury in Afghanistan who returned to duty still fared quite poorly on many clinical outcome measures 6-12 months after injury. Poor global outcome seems to be largely driven by psychological health measures, age, and traumatic brain injury status. The effects of early interventions and longer term implications of these findings are unknown.

  7. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  8. Main and interactive effects of shiftwork, age and work stress on health in an Italian sample of healthcare workers

    DEFF Research Database (Denmark)

    Conway, Paul Maurice; Campanini, P; Sartori, S

    2008-01-01

    Among healthcare workers, shiftwork (mostly if nightwork is also included), ageing and work-related stress may be factors leading to impaired health. Such risk factors may also operate in interaction, resulting in an even increased harm for health. The present study aims at evaluating...... gastrointestinal disorders, poor work ability and job dissatisfaction. Work stress was the risk factor with the highest relevance for poor health. Ageing was associated with lower physical health. Few significant interactions were observed. Shiftwork with nights and high work stress significantly interacted...

  9. Extended longevity mechanisms in short-lived progeroid mice: identification of a preservative stress response associated with successful aging.

    Science.gov (United States)

    van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B; Hasty, Paul; Suh, Yousin; van Steeg, Harry; Garinis, George A; Hoeijmakers, Jan H J; Mitchell, James R

    2007-01-01

    Semantic distinctions between "normal" aging, "pathological" aging (or age-related disease) and "premature" aging (otherwise known as segmental progeria) potentially confound important insights into the nature of each of the complex processes. Here we review a recent, unexpected discovery: the presence of longevity-associated characteristics typical of long-lived endocrine-mutant and dietary-restricted animals in short-lived progeroid mice. These data suggest that a subset of symptoms observed in premature aging, and possibly normal aging as well, may be indirect manifestations of a beneficial adaptive stress response to endogenous oxidative damage, rather than a detrimental result of the damage itself.

  10. Effects of Combined Foot Massage and Cognitive Behavioral Therapy on the Stress Response in Middle-Aged Women.

    Science.gov (United States)

    Lee, Young Mi; Yeun, Young Ran

    2017-06-01

    Several intervention studies have suggested that foot massage and cognitive behavioral therapy (CBT) are beneficial for reducing the stress response. However, no randomized control trials have been conducted to examine these effects in middle-aged women, who are more commonly exposed to stress relative to others. This study aimed to examine the effects of combined self-administered foot massage and CBT on the psychophysiological stress response in Korean middle-aged women. Randomized controlled trial. Subjects were recruited from the social welfare center in Sahmcheok, Kangwondo, Korea. The subjects performed some of the massage at the center and some at home, and CBT was performed at the center. Fifty-three women aged 45-64 years were randomly assigned to Group A (intervention, n = 31) or B (usual care, n = 30). Combined self-administered foot massage and CBT. Depression, anxiety, stress, blood pressure, heart rate, blood glucose (BG), and oxygen saturation were measured at baseline and 3-week follow-up. Mean depression scores (p = 0.021), stress scores (p = 0.009), systolic blood pressure (SBP) (p = 0.035), and BG levels (p = 0.007) had decreased significantly subsequent to the intervention. Combined self-administered foot massage and CBT led to reductions in depression, stress, SBP, and BG levels. Therefore, the intervention could be an effective means of reducing the stress response in middle-aged women.

  11. The impact of cortisol reactivity to acute stress on memory: sex differences in middle-aged people.

    Science.gov (United States)

    Almela, Mercedes; Hidalgo, Vanesa; Villada, Carolina; Espín, Laura; Gómez-Amor, Jesús; Salvador, Alicia

    2011-03-01

    Stress has been identified as a main factor involved in the cognitive changes that occur during the aging process. This study investigated sex differences in the relationship between the magnitude of the acute stress-induced salivary cortisol response and memory performance among middle-aged people. To this end, 16 men and 16 women (aged 54-72 years) were exposed to the Trier Social Stress Test and a control condition in a crossover design. Afterwards their memory performance was measured using a standardized memory test (Rey's Auditory Verbal Learning Test). Only among women, there was an acute impact of stress on memory performance and a significant relationship between a higher cortisol response to the stressor and poorer memory performance in both the stress and control conditions. Additionally, a poorer memory performance was related to earlier timing of sexual maturation (age at menarche), which was also marginally related to higher cortisol reactivity to stress. These results confirm that sex is a critical factor in the relationship between cortisol and poor memory performance. Furthermore, the findings emphasize a strong link between the individual cortisol response to stress and memory functioning among postmenopausal women.

  12. Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

    Directory of Open Access Journals (Sweden)

    Korsak Kris

    2012-08-01

    Full Text Available Abstract Background Ageing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF and neurotrophin-3 (NT-3 have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells. Results Analysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL and calorically-restricted (CR animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells. Conclusions The neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b isoform occurred in 24 m AL animals. GDNF, but not

  13. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (pEPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (pEPO (r=-0.701, pEPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability.

  14. [Understanding a hospitalized, school-aged child's stress in the PICU: the application of picture books in nursing care].

    Science.gov (United States)

    Wang, Pei-Ju; Feng, Jui-Ying

    2013-06-01

    Hospitalization in the pediatric intensive care unit (PICU) can be a very stressful and sometimes traumatic experience for school-aged children due to illness, painful procedures, unfamiliar environment, and separation from family. We incorporated picture books into PICU nursing care to explore the stress response in a school-aged child with compartment syndrome who was hospitalized in the PICU. Observation, interview and communication with the patient were used to assess her psychological reactions and emotional and behavioral responses to stress related to hospitalization and medical treatment. Autonomy and control were provided and strengthened by giving the patient choices and purposive life plans. Picture books were used to establish rapport and help the patient express her feelings, needs, and desires for parental love and company. This case report highlights the importance of nurses' awareness of children's stresses and needs during hospitalization in the PICU as well as the value of picture books or other age-appropriate tools for this patient population.

  15. The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress.

    Science.gov (United States)

    Skibska, Beata; Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

  16. Exploring the role of genetic variability and lifestyle in oxidative stress response for healthy aging and longevity.

    Science.gov (United States)

    Dato, Serena; Crocco, Paolina; D'Aquila, Patrizia; de Rango, Francesco; Bellizzi, Dina; Rose, Giuseppina; Passarino, Giuseppe

    2013-08-08

    Oxidative stress is both the cause and consequence of impaired functional homeostasis characterizing human aging. The worsening efficiency of stress response with age represents a health risk and leads to the onset and accrual of major age-related diseases. In contrast, centenarians seem to have evolved conservative stress response mechanisms, probably derived from a combination of a diet rich in natural antioxidants, an active lifestyle and a favorable genetic background, particularly rich in genetic variants able to counteract the stress overload at the level of both nuclear and mitochondrial DNA. The integration of these factors could allow centenarians to maintain moderate levels of free radicals that exert beneficial signaling and modulator effects on cellular metabolism. Considering the hot debate on the efficacy of antioxidant supplementation in promoting healthy aging, in this review we gathered the existing information regarding genetic variability and lifestyle factors which potentially modulate the stress response at old age. Evidence reported here suggests that the integration of lifestyle factors (moderate physical activity and healthy nutrition) and genetic background could shift the balance in favor of the antioxidant cellular machinery by activating appropriate defense mechanisms in response to exceeding external and internal stress levels, and thus possibly achieving the prospect of living a longer life.

  17. The plasma membrane redox system: a candidate source of aging-related oxidative stress.

    Science.gov (United States)

    de Grey, Aubrey D N J

    2005-06-01

    The plasma membrane redox system (PMRS) is an electron transport chain in the plasma membrane that transfers electrons from either intra- or extracellular donors to extracellular acceptors. Unlike the superoxide-generating NADPH oxidase of phagocytes and the homologous (but much less active) enzymes found in some other cells, the PMRS is still incompletely characterised at the molecular level. Much is known, however, concerning its function and affinity for both physiological and non-physiological substrates. A role for it in aging, the 'reductive hotspot hypothesis' (RHH), was proposed in 1998 as part of an explanation for the apparently indefinite survival in vivo of cells that have entirely lost mitochondrial respiratory capacity as a result of the accumulation of mitochondrial mutations. Stimulation of the PMRS might allow the cell to maintain redox homeostasis even while continuing to operate the Krebs cycle, which may be advantageous in many ways. However, the PMRS may, like the mitochondrial respiratory chain, be prone to generate superoxide when thus dysregulated - and in this case superoxide would be generated outside the cell, where antioxidant defences are more limited than inside the cell and where much highly oxidisable material is present. Cascades of peroxidation chain reactions initiated by this process may greatly amplify the oxidative stress on the organism that is caused by rare mitochondrially mutant cells. Since such cells increase in abundance with aging (though remaining rare), this is an economical hypothesis to explain the rise in oxidative stress seen in (and generally believed to contribute substantially to) mammalian aging. In an extension of previously published accounts of RHH, I propose here that the lysosomal toxicity of oxidised cholesterol derivatives (oxysterols) may contribute to the toxicity of mitochondrial mutations by affecting lysosomal function in many cell types in the same way as they have been proposed to do in arterial

  18. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  19. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    Science.gov (United States)

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  20. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  1. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

    Directory of Open Access Journals (Sweden)

    Nady Braidy

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

  2. The Effect of Aging on Mitochondrial Complex I and the Extent of Oxidative Stress in the Rat Brain Cortex.

    Science.gov (United States)

    Tatarkova, Zuzana; Kovalska, Maria; Timkova, Veronika; Racay, Peter; Lehotsky, Jan; Kaplan, Peter

    2016-08-01

    One of the characteristic features of the aging is dysfunction of mitochondria. Its role in the regulation of metabolism and apoptosis suggests a possible link between these cellular processes. This study investigates the relationship of respiratory complex I with aging-related oxidative stress in the cerebral mitochondria. Deterioration of complex I seen in senescent (26-months old) mitochondria was accompanied by decline in total thiol group content, increase of HNE and HNE-protein adducts as well as decreased content of complex I subunits, GRIM-19 and NDUFV2. On the other hand, decline of complex I might be related with the mitochondrial apoptosis through increased Bax/Bcl-2 cascade in 15-month old animal brains. Higher amount of Bcl-2, Bcl-xL with the lower content of GRIM-19 could maintain to some extent elevated oxidative stress in mitochondria as seen in the senescent group. In the cortical M1 region increased presence of TUNEL+ cells and more than 20-times higher density of Fluoro-Jade C+ cells in 26-months old was observed, suggesting significant neurodegenerative effect of aging in the neuronal cells. Our study supports a scenario in which the age-related decline of complex I might sensitize neurons to the action of death agonists, such as Bax through lipid and protein oxidative stimuli in mitochondria. Although aging is associated with oxidative stress, these changes did not increase progressively with age, as similar extent of lesions was observed in oxidative stress markers of the both aged groups.

  3. Effect of aging on performance, muscle activation and perceived stress during mentally demanding computer tasks

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Pilegaard, Marianne; Bakke, Merete

    2005-01-01

    OBJECTIVES: This study examined the effects of age on performance, muscle activation, and perceived stress during computer tasks with different levels of mental demand. METHODS: Fifteen young and thirteen elderly women performed two computer tasks [color word test and reference task] with different...... demands affect young and elderly women differently. Thus the mentally demanding computer task had a more pronounced effect on the elderly than on the young. In contrast to the results in the reference task, the same level of muscle activity for most muscles and the same level of self-reported difficulty...... levels of mental demand but similar physical demands. The performance (clicking frequency, percentage of correct answers, and response time for correct answers) and electromyography from the forearm, shoulder, and neck muscles were recorded. Visual analogue scales were used to measure the participants...

  4. Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging.

    Science.gov (United States)

    Kögel, Donat; Deller, Thomas; Behl, Christian

    2012-04-01

    The roles of amyloid precursor protein (APP) family members in normal brain function are poorly understood. Under physiological conditions the majority of APP appears to be processed along the non-amyloidogenic pathway leading to the formation of the secreted N-terminal APP fragment sAPPα. This cleavage product of APP has been implicated in several physiological processes such as neuroprotection, synaptic plasticity, neurite outgrowth and synaptogenesis. In this review we focus on the role of APP family members in neuroprotection and summarize the cellular and molecular mechanisms which are believed to mediate this effect. We propose that a reduction of APP processing along the non-amyloidogenic pathway during brain aging could result in an enhanced susceptibility of neurons to cellular stress and could contribute to neurodegeneration in Alzheimer's disease.

  5. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    Science.gov (United States)

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

  6. Conservation of acquired morphology and community structure in aged biofilms after facing environmental stress.

    Science.gov (United States)

    Saur, T; Escudié, R; Santa-Catalina, G; Bernet, N; Milferstedt, K

    2016-01-01

    The influence of growth history on biofilm morphology and microbial community structure is poorly studied despite its important role for biofilm development. Here, biofilms were exposed to a change in hydrodynamic conditions at different growth stages and we observed how biofilm age affected the change in morphology and bacterial community structure. Biofilms were developed in two bubble column reactors, one operated under constant shear stress and one under variable shear stress. Biofilms were transferred from one reactor to the other at different stages in their development by withdrawing and inserting the support medium from one reactor to the other. The developments of morphology and microbial community structure were followed by image analysis and molecular tools. When transferred early in biofilm development, biofilms adapted to the new hydrodynamic conditions and adopted features of the biofilm already developed in the receiving reactor. Biofilms transferred at a late state of biofilm development continued their initial trajectories of morphology and community development even in a new environment. These biofilms did not immediately adapt to their new environment and kept features acquired during their early growth phase, a property we called memory effect.

  7. The importance of plasma membrane coenzyme Q in aging and stress responses.

    Science.gov (United States)

    Navas, Plácido; Villalba, José Manuel; de Cabo, Rafael

    2007-06-01

    The plasma membrane of eukaryotic cells is the limit to interact with the environment. This position implies receiving stress signals that affects its components such as phospholipids. Inserted inside these components is coenzyme Q that is a redox compound acting as antioxidant. Coenzyme Q is reduced by diverse dehydrogenase enzymes mainly NADH-cytochrome b(5) reductase and NAD(P)H:quinone reductase 1. Reduced coenzyme Q can prevent lipid peroxidation chain reaction by itself or by reducing other antioxidants such as alpha-tocopherol and ascorbate. The group formed by antioxidants and the enzymes able to reduce coenzyme Q constitutes a plasma membrane redox system that is regulated by conditions that induce oxidative stress. Growth factor removal, ethidium bromide-induced rho degrees cells, and vitamin E deficiency are some of the conditions where both coenzyme Q and its reductases are increased in the plasma membrane. This antioxidant system in the plasma membrane has been observed to participate in the healthy aging induced by calorie restriction. Furthermore, coenzyme Q regulates the release of ceramide from sphingomyelin, which is concentrated in the plasma membrane. This results from the non-competitive inhibition of the neutral sphingomyelinase by coenzyme Q particularly by its reduced form. Coenzyme Q in the plasma membrane is then the center of a complex antioxidant system preventing the accumulation of oxidative damage and regulating the externally initiated ceramide signaling pathway.

  8. Attenuation of replication stress-induced premature cellular senescence to assess anti-aging modalities.

    Science.gov (United States)

    Zhao, Hong; Darzynkiewicz, Zbigniew

    2014-01-01

    Described is an in vitro model of premature senescence in pulmonary adenocarcinoma A549 cells induced by persistent DNA replication stress in response to treatment with the DNA damaging drug mitoxantrone (Mxt). The degree of cellular senescence, based on characteristic changes in cell morphology, is measured by laser scanning cytometry. Specifically, the flattening of cells grown on slides (considered the hallmark of cellular senescence) is measured as the decline in local intensity of DNA-associated DAPI fluorescence (represented by maximal pixels). This change is paralleled by an increase in nuclear area. Thus, the ratio of mean intensity of maximal pixels to nuclear area provides a very sensitive morphometric biomarker for the degree of senescence. This analysis is combined with immunocytochemical detection of senescence markers, such as overexpression of cyclin kinase inhibitors (e.g., p21(WAF1) ) and phosphorylation of ribosomal protein S6 (rpS6), a key marker associated with aging/senescence that is detected using a phospho-specific antibody. These biomarker indices are presented in quantitative terms defined as a senescence index (SI), which is the fraction of the marker in test cultures relative to the same marker in exponentially growing control cultures. This system can be used to evaluate the anti-aging potential of test agents by assessing attenuation of maximal senescence. As an example, the inclusion of berberine, a natural alkaloid with reported anti-aging properties and a long history of use in traditional Chinese medicine, is shown to markedly attenuate the Mxt-induced SI and phosphorylation of rpS6. The multivariate analysis of senescence markers by laser scanning cytometry offers a promising tool to explore the potential anti-aging properties of a variety agents.

  9. Plasma membrane Ca2+-ATPases:Targets of oxidative stress in brain aging and neurodegeneration

    Institute of Scientific and Technical Information of China (English)

    Asma; Zaidi

    2010-01-01

    The plasma membrane Ca2+-ATPase(PMCA)pumps play an important role in the maintenance of precise levels of intracellular Ca2+[Ca2+]i,essential to the functioning of neurons.In this article,we review evidence showing age-related changes of the PMCAs in synaptic plasma membranes(SPMs).PMCA activity and protein levels in SPMs diminish progressively with increasing age. The PMCAs are very sensitive to oxidative stress and undergo functional and structural changes when exposed to oxidants of physiological relevance.The major signatures of oxidative modification in the PMCAs are rapid inactivation,conformational changes,aggregation, internalization from the plasma membrane and proteolytic degradation.PMCA proteolysis appears to be mediated by both calpains and caspases.The predominance of one proteolytic pathway vs the other,the ensuing pattern of PMCA degradation and its consequence on pump activity depends largely on the type of insult,its intensity and duration.Experimental reduction of PMCA expression not only alters the dynamics of cellular Ca2+ handling but also has a myriad of downstream conse-quences on various aspects of cell function,indicating a broad role of these pumps.Age-and oxidation-related down-regulation of the PMCAs may play an important role in compromised neuronal function in the aging brain and its several-fold increased susceptibility to neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease,and stroke.Therapeutic approaches that protect the PMCAs and stabilize[Ca2+]i homeostasis may be capable of slowing and/or preventing neuronal degeneration.The PMCAs are therefore emerging as a new class of drug targets for therapeutic interventions in various chronic degenerative disorders.

  10. Nocturnal hyperthermia induced by social stress in male tree shrews: relation to low testosterone and effects of age.

    Science.gov (United States)

    Kohlhause, Susan; Hoffmann, Kerstin; Schlumbohm, Christina; Fuchs, Eberhard; Flügge, Gabriele

    2011-10-24

    Stress is known to elevate core body temperature (CBT). We recorded CBT in a diurnal animal, the male tree shrew, during a one-week control period and a one-week period of social stress using a telemetric system. During the stress period, when animals were confronted with a dominant male for about 1h daily, CBT was increased throughout the day. We analyzed CBT during the night when animals were left undisturbed and displayed no locomotor activity. To determine whether nocturnal hyperthermia may be related to stress-induced changes in hormonal status, we measured testosterone, noradrenalin and cortisol in the animals' morning urine. The daily social stress increased the mean nocturnal temperature by 0.37 °C. Urinary testosterone was reduced during the stress period, and there was a significant negative correlation between testosterone and the area under the curve (AUC) of the nocturnal CBT. This means that stress-induced hyperthermia was strongest in the animals with the lowest testosterone concentrations. As expected, urinary noradrenalin was elevated during the stress week but a positive correlation with the AUC data was only found for animals younger than 12 months. Cortisol was also increased during the stress week but there were no correlations with nocturnal hyperthermia. However, the stress-induced increases in noradrenalin and cortisol correlated with each other. Furthermore, there were no correlations between the stress-induced increase in nocturnal CBT and body weight reduction or locomotor activity during the light phase. Interestingly, the extent of nocturnal hyperthermia depended on the animals' ages: In animals younger than 12 months, stress increased the AUC by 48%, in animals aged between 12 and 24 months, stress increased the AUC by 36%, and older animals showed only a 7% increase. However, testosterone was not significantly reduced in the older animals. The present data reveal an interrelation between the extent of stress-induced nocturnal

  11. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  12. The relationship between psychosocial stress, age, BMI, CRP, lifestyle, and the metabolic syndrome in apparently healthy subjects.

    Science.gov (United States)

    Yamamoto, Kazuhiko; Okazaki, Ai; Ohmori, Susumu

    2011-01-01

    The aim of this cross-sectional study was to examine the factors which may be associated with the metabolic syndrome by exploring the relationship between psychosocial stress, age, body mass index (BMI), C-reactive protein (CRP), lifestyle factors, and the components of the metabolic syndrome, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), body fat percentage, and triglyceride concentration, among apparently healthy subjects. Psychosocial stress was measured by the use of the inventory to measure psychosocial stress (IMPS). One thousand four hundred and ninety-nine people out of 1,941 public school workers admitted to a hospital for a medical check-up responded to the IMPS, yielding a response rate of 77.2%. A total of 1,201 workers excluding 298 who were taking medication for various diseases were analyzed with the use of hierarchical multiple regression models. It was found that IMPS-measured stress score, age, BMI, and smoking habit were associated with an increase in glycated hemoglobin among men, while alcohol consumption was associated with a decrease in glycated hemoglobin. Stress score, age, BMI, and alcohol consumption were found to be associated with an increase in FBS among men, while smoking and exercise habits were associated with a decrease in FBS. CRP was found to be associated with an increase in body fat percentage among men, though stress score was not associated with an increase in body fat percentage. Stress score, age, and BMI were associated with an increase in triglyceride concentration among women. The findings of the present study seem to be in line with the hypothesis that psychosocial stress plays an important role in developing the metabolic syndrome, which may be associated with inflammatory processes in the vascular wall, resulting in atherosclerosis and cardiovascular disease.

  13. Determination of the Thermal Expansion Coefficient of Concrete at Early Ages by Using Temperature-stress Testing Machine

    Institute of Scientific and Technical Information of China (English)

    HUO Kaicheng; SHUI Zhonghe; LI Yue

    2006-01-01

    By using the uptodate temperatuer-stress testing machine, the thermal expansion coefficient of concrete at early ages was studied and indicative conclusions were achieved: temperature rising due to hydration heat is not directly correlated with cracking, but the temperature and stress evolution process should be taken into consideration in the same time. Proper chemical admixtures and mineral compositions can improve the mechanical properties of concrete such as thermal expansion coefficient, which is very indicative in practice.

  14. A facilitator of leisure activities for stress-related growth experience among middle-aged Korean women with depression.

    Science.gov (United States)

    Kim, Junhyoung; Kim, Jung-Hyun

    2014-01-01

    Leisure may serve as a coping resource following negative life events that facilitate positive changes. Previous studies on leisure have mainly focused on stress-related growth among individuals living in Western cultures. This study aimed to capture the role of leisure involvement as a facilitator of stress-related growth among middle-aged Korean women with depression. Three main themes were identified as an outcome of participation in leisure activities: (a) strengthening meaningful relationships, (b) improving positive emotions, and (c) facilitating personal strength. By participating in leisure activities, individuals with depression may develop the ability to cope with stress and experience positive changes.

  15. Interaction between diazepam and hippocampal corticosterone after acute stress: impact on memory in middle-aged mice

    Directory of Open Access Journals (Sweden)

    Daniel eBeracochea

    2011-04-01

    Full Text Available Benzodiazepines (BDZ are widely prescribed in the treatment of anxiety disorders associated to aging. Interestingly, whereas a reciprocal interaction between the GABAergic system and HPA axis has been evidenced, there is to our knowledge no direct evaluation of the impact of BDZ on both hippocampus (HPC corticosterone concentrations and HPC-dependent memory in stressed middle-aged subjects. We showed previously that an acute stress induced in middle-aged mice severe memory impairments in a hippocampus-dependent task, and increased in parallel hippocampus corticosterone concentrations, as compared to non stressed middle-aged controls (Tronche et al., 2010. Based on these findings, the aims of the present study were to evidence the impact of diazepam (a positive allosteric modulator of the GABA-A receptor on HPC glucocorticoids concentrations and in parallel on HPC-dependent memory in acutely stressed middle-aged mice.Microdialysis experiments showed an interaction between diazepam doses and corticosterone concentrations into the HPC. From 0.25 mg/kg to 0.5 mg/kg, diazepam dose-dependently reduces intra-HPC corticosterone concentrations and in parallel, dose-dependently increased hippocampal-dependent memory performance. In contrast, the highest (1.0mg/kg diazepam dose induces a reduction in HPC corticosterone concentration, which was of greater magnitude as compared to the two other diazepam doses, but however decreased the hippocampal-dependent memory performance. In summary, our study provides first evidence that diazepam restores in stressed middle-aged animals the hippocampus-dependent response, in relation with HPC corticosterone concentrations. Overall, our data illustrate how stress and benzodiazepines could modulate cognitive functions depending on hippocampus activity.

  16. PnLRR-RLK27, a novel leucine-rich repeats receptor-like protein kinase from the Antarctic moss Pohlia nutans, positively regulates salinity and oxidation-stress tolerance

    Science.gov (United States)

    Wang, Jing; Liu, Shenghao; Li, Chengcheng; Wang, Tailin; Chen, Kaoshan

    2017-01-01

    Leucine-rich repeats receptor-like kinases (LRR-RLKs) play important roles in plant growth and development as well as stress responses. Here, 56 LRR-RLK genes were identified in the Antarctic moss Pohlia nutans transcriptome, which were further classified into 11 subgroups based on their extracellular domain. Of them, PnLRR-RLK27 belongs to the LRR II subgroup and its expression was significantly induced by abiotic stresses. Subcellular localization analysis showed that PnLRR-RLK27 was a plasma membrane protein. The overexpression of PnLRR-RLK27 in Physcomitrella significantly enhanced the salinity and ABA tolerance in their gametophyte growth. Similarly, PnLRR-RLK27 heterologous expression in Arabidopsis increased the salinity and ABA tolerance in their seed germination and early root growth as well as the tolerance to oxidative stress. PnLRR-RLK27 overproduction in these transgenic plants increased the expression of salt stress/ABA-related genes. Furthermore, PnLRR-RLK27 increased the activities of reactive oxygen species (ROS) scavengers and reduced the levels of malondialdehyde (MDA) and ROS. Taken together, these results suggested that PnLRR-RLK27 as a signaling regulator confer abiotic stress response associated with the regulation of the stress- and ABA-mediated signaling network. PMID:28241081

  17. Stress resilience in adolescence and subsequent antidepressant and anxiolytic medication in middle aged men: Swedish cohort study.

    Science.gov (United States)

    Hiyoshi, Ayako; Udumyan, Ruzan; Osika, Walter; Bihagen, Erik; Fall, Katja; Montgomery, Scott

    2015-06-01

    It is unclear whether psychological resilience to stress in adolescence represents a persistent characteristic relevant to the subsequent risk for depression and anxiety in later adulthood. We aimed to test whether low psychological stress resilience assessed in adolescence is associated with an increased risk of receiving medication for depression and anxiety in middle age. We utilized Swedish register-based cohort study. Men born between 1952 and 1956 (n = 175,699), who underwent compulsory assessment for military conscription in late adolescence were followed to examine subsequent risk of pharmaceutically-treated depression and anxiety in middle age, from 2006 to 2009 corresponding to ages between 50 and 58 years, using Cox regression. The associations of stress resilience with prescription of antidepressant and anxiolytics medication through potential mediating factors cognitive and physical function and adult socioeconomic factors were calculated. Low stress resilience was associated with elevated risks for antidepressant (hazard ratio (HR):1.5 (95% CI 1.4 1.6)) and anxiolytics (HR:2.4 (CI 2.0 2.7)) medication. Adjustment for measures of childhood living circumstances attenuated the associations somewhat. Around a third of association with low stress resilience, and a half of that with moderate resilience, was mediated through cognitive and physical function in adolescence and adult socioeconomic factors. The magnitude of the inverse association of higher cognitive function with antidepressant medication was eliminated among those with low stress resilience. These results indicate that low stress resilience in adolescence is associated with an increased risk for antidepressant and anxiolytics medication over 30 years later, in part mediated through developmental factors in adolescence and socioeconomic circumstances in adulthood, and low stress resilience can diminish or eliminate the inverse association of higher cognitive function with antidepressant

  18. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    Science.gov (United States)

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  19. Does Maternal Prenatal Stress Adversely Affect the Child's Learning and Memory at Age Six?

    Science.gov (United States)

    Gutteling, Barbara M.; de Weerth, Carolina; Zandbelt, Noortje; Mulder, Eduard J. H.; Visser, Gerard H. A.; Buitelaar, Jan K.

    2006-01-01

    Prenatal maternal stress has been shown to affect postnatal development in animals and humans. In animals, the morphology and function of the offspring's hippocampus is negatively affected by prenatal maternal stress. The present study prospectively investigated the influence of prenatal maternal stress on learning and memory of 112 children (50…

  20. Moderating Effects of Gender on Outcomes Associated with Stressful Life Events Among Elementary School-Age Youth.

    Science.gov (United States)

    Brown, Shaquanna; Fite, Paula J; Poquiz, Jonathan

    2016-08-01

    Stressful life events have been associated with child and adolescent maladjustment, including elevated levels of aggression and anxiety (Attar et al. in J Clin Child Psychol 23:391-400, 1994; Fox et al. in J Adolesc 33:43-54, 2010). However, gender specific outcomes associated with stressful life events among elementary school-age youth are less known. Accordingly, the current study examined the role of gender in the associations between stressful life events and anxiety and proactive and reactive aggression. Participants included 294 elementary school-age children (M = 8.71, SD = 1.17, 50.7 % male). Regression analyses indicated that stressful life events were positively associated with anxiety and reactive, but not proactive, aggression. There were no gender differences with regard to the associations with anxiety symptoms or proactive aggression. However, gender moderated the association between stressful life events and reactive aggression, such that stressful life events were only positively associated with reactive aggression for boys. Future directions and implications of this research are presented.

  1. Hsp72 is present in plasma from Holstein-Friesian dairy cattle, and the concentration level is repeatable across days and age classes

    OpenAIRE

    Nygaard Kristensen, Torsten; Løvendahl, Peter; Berg, Peer; Loeschcke, Volker

    2004-01-01

    Although heat shock proteins (Hsps) are primarily considered as being intracellular, this study identified the presence of Hsp72 in plasma from female Holstein-Friesian dairy cattle. Plasma samples were collected from the same animals at different ages and on different days after calving and accordingly divided into 5 age classes. The age classes were calves less than 235 days of age, young heifers between 235 and 305 days of age, older heifers between 305 and 560 days of age, cows early in l...

  2. Stress

    Science.gov (United States)

    ... diabetes. Shopdiabetes.org: Your Stress-Free System for Family Dinners! - 2017-03-book-oclock-scramble.html Shopdiabetes.org Your Stress-Free System for Family Dinners! A year of delicious meals to help prevent ...

  3. Stress

    Science.gov (United States)

    ... sudden negative change, such as losing a job, divorce, or illness Traumatic stress, which happens when you ... stress, so you can avoid more serious health effects. NIH: National Institute of Mental Health

  4. Prelamin A accumulation and stress conditions induce impaired Oct-1 activity and autophagy in prematurely aged human mesenchymal stem cell.

    Science.gov (United States)

    Infante, Arantza; Gago, Andrea; de Eguino, Garbiñe Ruiz; Calvo-Fernández, Teresa; Gómez-Vallejo, Vanessa; Llop, Jordi; Schlangen, Karin; Fullaondo, Ane; Aransay, Ana M; Martín, Abraham; Rodríguez, Clara I

    2014-04-01

    Aging, a time-dependent functional decline of biological processes, is the primary risk factor in developing diseases such as cancer, cardiovascular or degenerative diseases. There is a real need to understand the human aging process in order to increase the length of disease-free life, also known as "health span". Accumulation of progerin and prelamin A are the hallmark of a group of premature aging diseases but have also been found during normal cellular aging strongly suggesting similar mechanisms between healthy aging and LMNA-linked progeroid syndromes. How this toxic accumulation contributes to aging (physiological or pathological) remains unclear. Since affected tissues in age-associated disorders and in pathological aging are mainly of mesenchymal origin we propose a model of human aging based on mesenchymal stem cells (hMSCs) which accumulate prelamin A. We demonstrate that prelamin A-accumulating hMSCs have a premature aging phenotype which affects their functional competence in vivo. The combination of prelamin A accumulation and stress conditions enhance the aging phenotype by dysregulating the activity of the octamer binding protein Oct-1This experimental model has been fundamental to identify a new role for Oct-1 in hMSCs aging.

  5. Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan.

    Science.gov (United States)

    Cai, Weijing; He, John C; Zhu, Li; Chen, Xue; Zheng, Feng; Striker, Gary E; Vlassara, Helen

    2008-08-01

    We previously showed that the content of advanced glycation end products (AGEs) in the diet correlates with serum AGE levels, oxidant stress (OS), organ dysfunction, and lifespan. We now show that the addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE mouse chow increased serum levels of AGEs and OS, demonstrating that dietary AGEs are oxidants that can induce systemic OS. OS predisposes to the development of cardiovascular and chronic kidney diseases; calorie restriction (CR) is the most studied means to decrease OS, increase longevity, and reduce OS-related organ damage in mammals. Because reduction of food intake also decreases oxidant AGE s intake, we asked whether the beneficial effects of CR in mammals are related to the restriction of oxidants or energy. Pair-fed mice were provided either a CR diet or a high-AGE CR diet in which AGEs were elevated by brief heat treatment (CR-high). Old CR-high mice developed high levels of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1 and GSH/GSSG levels, insulin resistance, marked myocardial and renal fibrosis, and shortened lifespan. In contrast, old CR mice had low OS, p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with longer lifespan. Therefore, the beneficial effects of a CR diet may be partly related to reduced oxidant intake, a principal determinant of oxidant status in aging mice, rather than decreased energy intake.

  6. Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer.

    Science.gov (United States)

    Pinti, Marcello; Gibellini, Lara; Liu, Yongzhang; Xu, Shan; Lu, Bin; Cossarizza, Andrea

    2015-12-01

    Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs.

  7. Does the oxidative stress theory of aging explain longevity differences in birds? I. Mitochondrial ROS production.

    Science.gov (United States)

    Montgomery, Magdalene K; Hulbert, A J; Buttemer, William A

    2012-03-01

    Mitochondrial reactive oxygen species (ROS) production rates are reported to be inversely related to maximum lifespan potential (MLSP) in mammals and also to be higher in short-living mammals compared to short-living birds. The mammal-bird comparison, however, is mainly based on studies of rats and pigeons. To date, there has been no systematic examination of ROS production in birds that differ in MLSP. Here we report a comparison of mitochondrial ROS production in two short-living (quails) and three long-living bird species (parrots) that exhibit, on average, a 5-fold longevity difference. Mitochondrial ROS production was determined both in isolated mitochondria (heart, skeletal muscle and liver) as traditionally done and also in intact erythrocytes. In all four tissues, mitochondrial ROS production was similar in quails and parrots and showed no correspondence with known longevity differences. The lack of a consistent difference between quails and parrots was not due to differences in mitochondrial content as ROS production in relation to oxygen consumption (determined as the free radical leak) showed a similar pattern. These findings cast doubt on the robustness of the oxidative stress theory of aging. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Oxidative Stress and Cardiovascular aging : Interaction between NRF-2 and ADMA.

    Science.gov (United States)

    Nair, Nandini; Gongora, Enrique

    2017-02-16

    BACKGROUND The concept of antioxidant therapies assumes high importance as oxidative stress is associated with cardiovascular aging via endothelial dysfunction. This review focusses on exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular function. OBJECTIVE A systematic review of literature from 1990 to 2016 was conducted using Pubmed and Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of DDAH I which degrades ADMA , the endogenous inhibitor of nitric oxide synthase . The resulting decrease of ADMA would in turn enhance nitric oxide (NO) production . This would support endothelial function by adequate NO production and homeostasis of endothelial function. CONCLUSIONS As NO production has many positive pleiotropic effects in the cardiovascular system, such an interaction could be utilized for designing molecular therapeutics. The targets for therapy need not be limited to activation of nrf-2. Modulation of molecules downstream such as DDAH I can be used to regulate ADMA levels. Most current literature is supported by animal studies. The concept of antioxidant therapies needs to be tested in well-defined randomized control trials. The biochemical basis of nrf-2 activation needs to be substantiated in human studies.

  9. Very pre-term infants' behaviour at 1 and 2 years of age and parental stress following basic developmental care

    NARCIS (Netherlands)

    Pal, S.M. van der; Maguire, C.M.; Bruil, J.; Cessie, S. le; Zwieten, P. van; Veen, S.; Wit, J.M.; Walther, F.J.

    2008-01-01

    This study explored the effects of basic developmental care on the behaviour of very pre-term infants and parental stress at I and 2 years of corrected age. A randomized controlled trial was done to compare basic Developmental Care (standardized nests and incubator covers) and controls (standard car

  10. Effect of Mitochondrial Oxidative Stress and Age on the Signaling Pathway of Ultrafine Particulate Matter Exposure in Murine Aorta

    Science.gov (United States)

    Epidemiological studies have linked ultrafine particulate matter (PM) exposure and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure. Advanced age is one ...

  11. Very pre-term infants' behaviour at 1 and 2 years of age and parental stress following basic developmental care

    NARCIS (Netherlands)

    Pal, S.M. van der; Maguire, C.M.; Bruil, J.; Cessie, S. le; Zwieten, P. van; Veen, S.; Wit, J.M.; Walther, F.J.

    2008-01-01

    This study explored the effects of basic developmental care on the behaviour of very pre-term infants and parental stress at I and 2 years of corrected age. A randomized controlled trial was done to compare basic Developmental Care (standardized nests and incubator covers) and controls (standard car

  12. Effect of Mitochondrial Oxidative Stress and Age on the Signaling Pathway of Ultrafine Particulate Matter Exposure in Murine Aorta

    Science.gov (United States)

    Epidemiological studies have linked ultrafine particulate matter (PM) exposure and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure. Advanced age is one ...

  13. Oxidative Stress and Protein Quality Control Systems in the Aged Canine Brain as a Model for Human Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Mariarita Romanucci

    2015-01-01

    Full Text Available Aged dogs are considered the most suitable spontaneous animal model for studying normal aging and neurodegenerative diseases. Elderly canines naturally develop cognitive dysfunction and neuropathological hallmarks similar to those seen in humans, especially Alzheimer’s disease-like pathology. Pet dogs also share similar living conditions and diets to humans. Oxidative damage accumulates in the canine brain during aging, making dogs a valid model for translational antioxidant treatment/prevention studies. Evidence suggests the presence of detective protein quality control systems, involving ubiquitin-proteasome system (UPS and Heat Shock Proteins (HSPs, in the aged canine brain. Further studies on the canine model are needed to clarify the role of age-related changes in UPS activity and HSP expression in neurodegeneration in order to design novel treatment strategies, such as HSP-based therapies, aimed at improving chaperone defences against proteotoxic stress affecting brain during aging.

  14. Effect of a novel three-step aging on strength, stress corrosion cracking and microstructure of AA7085

    Institute of Scientific and Technical Information of China (English)

    陈送义; 陈康华; 董朋轩; 叶升平; 黄兰萍; 阳代军

    2016-01-01

    The influence of a novel three-step aging on strength, stress corrosion cracking (SCC) and microstructure of AA7085 was investigated by tensile testing and slow strain rate testing combined with transmission electron microscopy (TEM). The results indicate that with the increase of second-step aging time of two-step aging, the mechanical properties increase first and then decrease, while the SCC resistance increases. Compared with two-step aging, three-step aging treatment improves SCC resistance and the strength increases by about 5%. The effects of novel three-step aging on strength and SCC resistance are explained by the role of matrix precipitates and grain boundary precipitates, respectively.

  15. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation1234

    Science.gov (United States)

    Patel, Sanjeet G; Guthikonda, Anuradha P; Reid, Marvin; Balasubramanyam, Ashok; Taffet, George E; Jahoor, Farook

    2011-01-01

    Background: Aging is associated with oxidative stress, but underlying mechanisms remain poorly understood. Objective: We tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. Design: Eight elderly and 8 younger subjects received stable-isotope infusions of [2H2]glycine, after which red blood cell (RBC) glutathione synthesis and concentrations, plasma oxidative stress, and markers of oxidant damage (eg, F2-isoprostanes) were measured. Elderly subjects were restudied after 2 wk of glutathione precursor supplementation. Results: Compared with younger control subjects, elderly subjects had markedly lower RBC concentrations of glycine (486.7 ± 28.3 compared with 218.0 ± 23.7 μmol/L; P glutathione (2.08 ± 0.12 compared with 1.12 ± 0.18 mmol/L RBCs; P glutathione fractional (83.14 ± 6.43% compared with 45.80 ± 5.69%/d; P glutathione concentration, a 78.8% higher fractional synthesis rate, a 230.9% higher absolute synthesis rate, and significantly lower plasma oxidative stress and F2-isoprostanes. No differences in these measures were observed between younger subjects and supplemented elderly subjects. Conclusions: Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging. PMID:21795440

  16. Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age.

    Science.gov (United States)

    Grunau, Ruth E; Cepeda, Ivan L; Chau, Cecil M Y; Brummelte, Susanne; Weinberg, Joanne; Lavoie, Pascal M; Ladd, Mihoko; Hirschfeld, Aaron F; Russell, Evan; Koren, Gideon; Van Uum, Stan; Brant, Rollin; Turvey, Stuart E

    2013-01-01

    Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very

  17. What is role of sex and age differences in marital conflict and stress of patients under Cardiac Rehabilitation Program?

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    Komasi, Saeid; Saeidi, Mozhgan

    2016-01-01

    BACKGROUND To investigate the role of sex and age differences in marital conflict and stress of patients who were under cardiac rehabilitation (CR) program. METHODS The data of this cross-sectional study were collected from the database of the CR Department of Imam Ali Hospital, Kermanshah, Iran. The demographics and medical data of 683 persons were collected from January 2003 and January 2010 using medical records, the Beck Anxiety Inventory, the Beck Depression Inventory, the Hudson’s Index of Marital Stress, and the Structured Clinical Interview for axis I disorders. Data were analyzed through Analysis of Covariance and Bonferroni test. RESULTS About 74.8% of the subjects were male. After adjustment for age, educational level, anxiety, and depression-the findings showed that women in CR program had a higher level of marital stress compared to men (54.75 ± 2.52 vs. 49.30 ± 0.89; P = 0.042). Furthermore, it was revealed that women who aged 56-65 years and more experienced higher level of marital stress compared to younger patients (P 0.050). CONCLUSION Marital conflict and stress threaten healthiness of women who aged 56-65 years more prominently than does in males or younger patients. Regarding the effect of marital stress on recurrence of the disease and cardiac-related morbidity and mortality in women, providing effective education and interventions to this group of patients, especially older women and even their spouses could be one of the useful objectives of CR programs. PMID:27752271

  18. The association between high levels of cumulative life stress and aberrant resting state EEG dynamics in old age.

    Science.gov (United States)

    Marshall, Amanda C; Cooper, Nicholas R

    2017-05-10

    Cumulative experienced stress produces shortcomings in old adults' cognitive performance. These are reflected in electrophysiological changes tied to task execution. This study explored whether stress-related aberrations in older adults' electroencephalographic (EEG) activity were also apparent in the system at rest. To this effect, the amount of stressful life events experienced by 60 young and 60 elderly participants were assessed in conjunction with resting state power changes in the delta, theta, alpha, and beta frequencies during a resting EEG recording. Findings revealed elevated levels of delta power among elderly individuals reporting high levels of cumulative life stress. These differed significantly from young high and low stress individuals and old adults with low levels of stress. Increases of delta activity have been linked to the emergence of conditions such as Alzheimer's Disease and Mild Cognitive Impairment. Thus, a potential interpretation of our findings associates large amounts of cumulative stress with an increased risk of developing age-related cognitive pathologies in later life. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence.

    Science.gov (United States)

    Höhn, Annika; Weber, Daniela; Jung, Tobias; Ott, Christiane; Hugo, Martin; Kochlik, Bastian; Kehm, Richard; König, Jeannette; Grune, Tilman; Castro, José Pedro

    2017-04-01

    Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Role of oxidative stress in age-related reduction of NO-cGMP-mediated vascular relaxation in SHR.

    Science.gov (United States)

    Payne, Jason A; Reckelhoff, Jane F; Khalil, Raouf A

    2003-09-01

    The incidence of hypertension increases during the late stages of aging; however, the vascular mechanisms involved are unclear. We investigated whether the late stages of aging are associated with impaired nitric oxide (NO)-mediated vascular relaxation and enhanced vascular contraction and whether oxidative stress plays a role in the age-related vascular changes. Aging (16 mo) male spontaneously hypertensive rats (SHR) nontreated or treated for 8 mo with the antioxidant tempol (1 mM in drinking water) or vitamin E (E; 5,000 IU/kg chow) and vitamin C (C; 100 mg. kg-1. day-1 in drinking water) and adult (12 wk) male SHR were used. After the arterial pressure was measured, aortic strips were isolated from the rats for measurement of isometric contraction. The arterial pressure and phenylephrine (Phe)-induced vascular contraction were enhanced, and the ACh-induced vascular relaxation and nitrite/nitrate production were reduced in aging compared with adult rats. In aging rats, the arterial pressure was nontreated (188 +/- 4), tempol-treated (161 +/- 6), and E + C-treated (187 +/- 1 mmHg). Phe (10-5 M) caused an increase in active stress in nontreated aging rats (14.3 +/- 1.0) that was significantly (P relaxation of Phe contraction in nontreated aging rats that was enhanced (P relaxation and enhanced Phe contraction in tempol- and E + C-treated but not the nontreated aging rats. ACh-induced vascular nitrite/nitrate production was not different in nontreated, tempol- and E + C-treated aging rats. Relaxation of Phe contraction with sodium nitroprusside, an exogenous NO donor, was smaller in aging than adult rats but was not different between nontreated, tempol- and E + C-treated aging rats. Thus, during the late stages of aging in SHR rats, an age-related inhibition of a vascular relaxation pathway involving not only NO production by endothelial cells but also the bioavailability of NO and the smooth muscle response to NO is partially reversed during chronic treatment with

  1. Stress buffering effects of social support on depressive symptoms in middle age: reciprocity and community mental health.

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    Takizawa, Tohru; Kondo, Tsuyoshi; Sakihara, Seizou; Ariizumi, Makoto; Watanabe, Naoki; Oyama, Hirofumi

    2006-12-01

    Little is known about the association between depression and the buffering effects of social support in mid-life crisis. The aim of this study is to determine the buffering effects of social support on depression concerning middle-aged individuals, while also taking reciprocity and gender differences into careful consideration. A cross-sectional survey of all middle-aged individuals (40-69 years of age) using a large sample (n = 4558) from a community-living population, who resided in Rokunohe town, Aomori prefecture in northern Japan (response rate = 69.8%), was undertaken. This town recently had a lot of suicides. Two-way anova was used to analyze the effects of stressor and social support on the Center for Epidemiologic Studies Depression scale scores. The authors found a stress buffering effect of social support on the depressive symptoms occurring in middle age, however, a significant difference in the stress buffer effect was only observed in male subjects. Moreover, when the authors take reciprocity into account, the effect of the buffer on depression was found not only in males receiving support but in males providing support as well. In conclusion, pertaining to males, social support reduces depressive symptoms under stressful circumstances in middle age, not only when they receive such support but also when they provide it. Therefore, these findings suggest that reciprocal social support is important for males in relation to community mental health.

  2. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    Science.gov (United States)

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  3. A longitudinal study of the impact of chronic psychological stress on health-related quality of life and clinical biomarkers: protocol for the Australian Healthy Aging of Women Study.

    Science.gov (United States)

    Seib, Charrlotte; Whiteside, Eliza; Humphreys, Janice; Lee, Kathryn; Thomas, Patrick; Chopin, Lisa; Crisp, Gabrielle; O'Keeffe, Angela; Kimlin, Michael; Stacey, Andrew; Anderson, Debra

    2014-01-08

    Despite advancements in our understanding of the importance of stress reduction in achieving good health, we still only have limited insight into the impact of stress on cellular function. Recent studies have suggested that exposure to prolonged psychological stress may alter an individual's physiological responses, and contribute to morbidity and mortality. This paper presents an overview of the study protocol we are using to examine the impact of life stressors on lifestyle factors, health-related quality of life and novel and established biomarkers of stress in midlife and older Australian women.The primary aim of this study is to explore the links between chronic psychological stress on both subjective and objective health markers in midlife and older Australian women. The study examines the extent to which exposure frightening, upsetting or stressful events such as natural disasters, illness or death of a relative, miscarriage and relationship conflict is correlated with a variety of objective and subjective health markers. This study is embedded within the longitudinal Healthy Aging of Women's study which has collected data from midlife and older Australian women at 5 yearly intervals since 2001, and uses the Allostastic model of women's health by Groër and colleagues in 2010. The current study expands the focus of the HOW study and will assess the impact of life stressors on quality of life and clinical biomarkers in midlife and older Australian women to explain the impact of chronic psychological stress in women. The proposed study hypothesizes that women are at increased risk of exposure to multiple or repeated stressors, some being unique to women, and the frequency and chronicity of stressors increases women's risk of adverse health outcomes. This study aims to further our understanding of the relationships between stressful life experiences, perceived quality of life, stress biomarkers, chronic illness, and health status in women.

  4. The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver.

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    Gong, Changxia; Li, Chengwei; Qi, Xiaoqing; Song, Zhiyin; Wu, Jianguo; Hughes, Michael E; Li, Xiaodong

    2015-01-01

    The circadian clock regulates many cellular processes, notably including the cell cycle, metabolism and aging. Mitochondria play essential roles in metabolism and are the major sites of reactive oxygen species (ROS) production in the cell. The clock regulates mitochondrial functions by driving daily changes in NAD(+) levels and Sirt3 activity. In addition to this central route, in the present study, we find that the expression of some mitochondrial genes is also rhythmic in the liver, and that there rhythms are disrupted by the Clock(Δ19) mutation in young mice, suggesting that they are regulated by the core circadian oscillator. Related to this observation, we also find that the regulation of oxidative stress is rhythmic in the liver. Since mitochondria and ROS play important roles in aging, and mitochondrial functions are also disturbed by aging, these related observations prompt the compelling hypothesis that circadian oscillators influence aging by regulating ROS in mitochondria. During aging, the expression rhythms of some mitochondrial genes were altered in the liver and the temporal regulation over the dynamics of mitochondrial oxidative stress was disrupted. However, the expression of clock genes was not affected. Our results suggested that mitochondrial functions are combinatorially regulated by the clock and other age-dependent mechanism(s), and that aging disrupts mitochondrial rhythms through mechanisms downstream of the clock.

  5. New Insights into the Role of Mitochondrial Dynamics and Autophagy during Oxidative Stress and Aging in the Heart

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ikeda

    2014-01-01

    Full Text Available The heart is highly sensitive to the aging process. In the elderly, the heart tends to become hypertrophic and fibrotic. Stiffness increases with ensuing systolic and diastolic dysfunction. Aging also affects the cardiac response to stress. At the molecular level, the aging process is associated with accumulation of damaged proteins and organelles, partially due to defects in protein quality control systems. The accumulation of dysfunctional and abnormal mitochondria is an important pathophysiological feature of the aging process, which is associated with excessive production of reactive oxygen species. Mitochondrial fusion and fission and mitochondrial autophagy are crucial mechanisms for maintaining mitochondrial function and preserving energy production. In particular, mitochondrial fission allows for selective segregation of damaged mitochondria, which are afterward eliminated by autophagy. Unfortunately, recent evidence indicates that mitochondrial dynamics and autophagy are progressively impaired over time, contributing to the aging process. This suggests that restoration of these mechanisms could delay organ senescence and prevent age-associated cardiac diseases. Here, we discuss the current understanding of the close relationship between mitochondrial dynamics, mitophagy, oxidative stress, and aging, with a particular focus on the heart.

  6. Effect of paraquat-induced oxidative stress on gene expression and aging of the filamentous ascomycete Podospora anserina

    Directory of Open Access Journals (Sweden)

    Matthias Wiemer

    2014-06-01

    Full Text Available Aging of biological systems is influenced by various factors, conditions and processes. Among others, processes allowing organisms to deal with various types of stress are of key importance. In particular, oxidative stress as the result of the generation of reactive oxygen species (ROS at the mitochondrial respiratory chain and the accumulation of ROS-induced molecular damage has been strongly linked to aging. Here we view the impact of ROS from a different angle: their role in the control of gene expression. We report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina grown on medium containing paraquat (PQ. This treatment leads to an increased cellular generation and release of H2O2, a reduced growth rate, and a decrease in lifespan. The combined challenge by PQ and copper has a synergistic negative effect on growth and lifespan. The data from the transcriptome analysis of the wild type cultivated under PQ-stress and their comparison to those of a longitudinal aging study as well as of a copper-uptake longevity mutant of P. anserina revealed that PQ-stress leads to the up-regulation of transcripts coding for components involved in mitochondrial remodeling. PQ also affects the expression of copper-regulated genes suggesting an increase of cytoplasmic copper levels as it has been demonstrated earlier to occur during aging of P. anserina and during senescence of human fibroblasts. This effect may result from the induction of the mitochondrial permeability transition pore via PQ-induced ROS, leading to programmed cell death as part of an evolutionary conserved mechanism involved in biological