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BackgroundIn the ASE/AIE-mediated genetic mechanism for age-related gene regulation, a recently identified age-related homeostasis mechanism, two genetic elements, ASE (age-related...Full Text Available
Age-Related Changes in Processing Speed: Unique Contributions of Cerebellar and Prefrontal Cortex
Full Text Available.Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology.
Recommendations for the treatment of aging in standard technical specifications
As part of the US Nuclear Regulatory Commission`s Nuclear Plant Aging Research Program, Pacific Northwest Laboratory (PNL) evaluated the standard technical specifications for nuclear power plants to determine whether the current surveillance requirements (SRs) were effective in detecting age-related degradation. Nuclear Plant Aging Research findings for selected systems and components were reviewed to identify the stressors and operative aging mechanisms and to evaluate the methods available to detect, differentiate, and trend the resulting aging degradation. Current surveillance and testing requirements for these systems and components were reviewed for their effectiveness in detecting degraded conditions and for potential contributions to premature degradation. When the current surveillance and testing requirements appeared ineffective in detecting aging degradation or potentially could contribute to premature degradation, a possible deficiency in the SRs was identified that could result in undetected degradation. Based on this evaluation, PNL developed recommendations for inspection, surveillance, trending, and condition monitoring methods to be incorporated in the SRs to better detect age- related degradation of these selected systems and components.
Recommendations for the treatment of aging in standard technical specifications
1995-09-01
As part of the US Nuclear Regulatory Commission`s Nuclear Plant Aging Research Program, Pacific Northwest Laboratory (PNL) evaluated the standard technical specifications for nuclear power plants to determine whether the current surveillance requirements (SRs) were effective in detecting age-related degradation. Nuclear Plant Aging Research findings for selected systems and components were reviewed to identify the stressors and operative aging mechanisms and to evaluate the methods available to detect, differentiate, and trend the resulting aging degradation. Current surveillance and testing requirements for these systems and components were reviewed for their effectiveness in detecting degraded conditions and for potential contributions to premature degradation. When the current surveillance and testing requirements appeared ineffective in detecting aging degradation or potentially could contribute to premature degradation, a possible deficiency in the SRs was identified that could result in undetected degradation. Based on this evaluation, PNL developed recommendations for inspection, surveillance, trending, and condition monitoring methods to be incorporated in the SRs to better detect age- related degradation of these selected systems and components.
State-of-the-art on aging of nuclear power plant containment structures
2001-05-01
During the life time of nuclear power plants, the concrete properties and structural integrity of safety related concrete structures are degraded due to various aging mechanism such as steel corrosion, erosion, fatigue, concrete cracking, creep and loss of prestress and other effects depending on the internal and external environemntal stressors and operating history. These concrete structural aging mechanic can increase the probability of initiation of age-related degradation with the passage of operating time through minor construction defects, such as cracks and inadequate water proofing, accelerate the potential age-related degradation, and significantly affect the safety and economics of structures. The containment is a vital engineering safety feature of a nuclear power plant. In domestic plant case, it is not sufficient that operating experienced-besed information and reports which contain aging factors, safety-ralated concrete structural material and constructive characteristics considered the various age-related degradation. The objective of this research is to identify for a state-of-the-art on aging issues, aging examples of NPP structures.
Life testing of a low voltage air circuit breaker
A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradation in the various breaker subcomponents, specifically the power-operated mechanism. This accelerated aging test was performed on one breaker unit for over 36,000 cycles. Three separate pole shafts, one with a 60-degree weld, one with a 120-degree weld, and one with a 180-degree weld in the third pole lever were used to characterize cracking in the welds. In addition, during the testing three different operating mechanisms and several other parts were replaced as they became inoperable. Among the seven welds on the pole shaft, {number_sign}1 and {number_sign}3 were found to be critical ones whose fracture can result in misalignment of the pole levers. This can lead to problems with the operating mechanism, including the burning of coils, excessive wear in certain parts, and overstressed linkages. Furthermore, the limiting service life of a number of subcomponents of the power-operated mechanism, including the operating mechanism itself, were assessed. Based on these findings, suggestions are provided to alleviate the age-related degradation that could occur as a result of normal closing and opening of the breaker contacts during its service life. Also, cause and effect analyses of various age-related degradation in various breaker parts are discussed.
Life testing of a low voltage air circuit breaker
A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradation in the various breaker subcomponents, specifically the power-operated mechanism. This accelerated aging test was performed on one breaker unit for over 36,000 cycles. Three separate pole shafts, one with a 60-degree weld, one with a 120-degree weld, and one with a 180-degree weld in the third pole lever were used to characterize cracking in the welds. In addition, during the testing three different operating mechanisms and several other parts were replaced as they became inoperable. Among the seven welds on the pole shaft, {number sign}1 and {number sign}3 were found to be critical ones whose fracture can result in misalignment of the pole levers. This can lead to problems with the operating mechanism, including the burning of coils, excessive wear in certain parts, and overstressed linkages. Furthermore, the limiting service life of a number of subcomponents of the power-operated mechanism, including the operating mechanism itself, were assessed. Based on these findings, suggestions are provided to alleviate the age-related degradation that could occur as a result of normal closing and opening of the breaker contacts during its service life. Also, cause and effect analyses of various age-related degradation in various breaker parts are discussed.
Life testing of a low voltage air circuit breaker
1992-01-01
A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradation in the various breaker subcomponents, specifically the power-operated mechanism. This accelerated aging test was performed on one breaker unit for over 36,000 cycles. Three separate pole shafts, one with a 60-degree weld, one with a 120-degree weld, and one with a 180-degree weld in the third pole lever were used to characterize cracking in the welds. In addition, during the testing three different operating mechanisms and several other parts were replaced as they became inoperable. Among the seven welds on the pole shaft, {number sign}1 and {number sign}3 were found to be critical ones whose fracture can result in misalignment of the pole levers. This can lead to problems with the operating mechanism, including the burning of coils, excessive wear in certain parts, and overstressed linkages. Furthermore, the limiting service life of a number of subcomponents of the power-operated mechanism, including the operating mechanism itself, were assessed. Based on these findings, suggestions are provided to alleviate the age-related degradation that could occur as a result of normal closing and opening of the breaker contacts during its service life. Also, cause and effect analyses of various age-related degradation in various breaker parts are discussed.
Life testing of a low voltage air circuit breaker
1992-06-01
A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradation in the various breaker subcomponents, specifically the power-operated mechanism. This accelerated aging test was performed on one breaker unit for over 36,000 cycles. Three separate pole shafts, one with a 60-degree weld, one with a 120-degree weld, and one with a 180-degree weld in the third pole lever were used to characterize cracking in the welds. In addition, during the testing three different operating mechanisms and several other parts were replaced as they became inoperable. Among the seven welds on the pole shaft, {number_sign}1 and {number_sign}3 were found to be critical ones whose fracture can result in misalignment of the pole levers. This can lead to problems with the operating mechanism, including the burning of coils, excessive wear in certain parts, and overstressed linkages. Furthermore, the limiting service life of a number of subcomponents of the power-operated mechanism, including the operating mechanism itself, were assessed. Based on these findings, suggestions are provided to alleviate the age-related degradation that could occur as a result of normal closing and opening of the breaker contacts during its service life. Also, cause and effect analyses of various age-related degradation in various breaker parts are discussed.
Detecting and mitigating aging in component cooling water systems
1991-01-01
The time-dependent effects of aging on component cooling water (CCW) systems in nuclear power plants has been studied and documented as part of a research program sponsored by the US Nuclear Regulatory Commission. It was found that age related degradation leads to failures in the CCW system which can result in an increase in system unavailability, if not properly detected and mitigated. To identify effective methods of managing this degradation, information on inspection, monitoring, and maintenance practices currently available was obtained from various operating plants and reviewed. The findings were correlated with the most common aging mechanisms and failure modes and a compilation of aging detection and mitigation practices was formulated. This paper discusses the results of this work.
Omega version 2.2: Rule-based deterioration identification and management system. Final report
1996-01-01
This report presents the Omega Version 2.2 (OMEGAs) rule-based computer program for identifying material deteriorations in the metallic structures, systems and components of LWR nuclear power units. The basis of Us is that understanding what material deteriorations might occur as a function of service life is fundamental to: (1) the development and optimization of preventive maintenance programs, (2) ensuring that current maintenance programs recognize applicable degradations, and (3) demonstrating the adequacy of deterioration management to safety regulatory authorities. The system was developed to assist utility engineers in determining which aging degradation mechanisms are acting on specific components. Direction is also provided to extend this system to manage deterioration and evaluate the efficacy of existing age-related degradation ...
Detecting and mitigating aging in component cooling water systems
1992-01-01
The time-dependent effects of aging on component cooling water (CCW) systems in nuclear power plants has been studied and documented as part of a research program sponsored by the US Nuclear Regulatory Commission. It was found that age related degradation leads to failures in the CCW system which can result in an increase in system unavailability, if not properly detected and mitigated. To identify effective methods of managing this degradation, information on inspection, monitoring, and maintenance practices currently available was obtained from various operating plants and reviewed. The findings were correlated with the most common aging mechanisms and failure modes, and a compilation of aging detection and mitigation practices was formulated. This paper discusses the results of this work.
Detecting and mitigating aging in component cooling water systems
1992-06-01
The time-dependent effects of aging on component cooling water (CCW) systems in nuclear power plants has been studied and documented as part of a research program sponsored by the US Nuclear Regulatory Commission. It was found that age related degradation leads to failures in the CCW system which can result in an increase in system unavailability, if not properly detected and mitigated. To identify effective methods of managing this degradation, information on inspection, monitoring, and maintenance practices currently available was obtained from various operating plants and reviewed. The findings were correlated with the most common aging mechanisms and failure modes, and a compilation of aging detection and mitigation practices was formulated. This paper discusses the results of this work.
Detecting and mitigating aging in component cooling water systems
1991-12-31
The time-dependent effects of aging on component cooling water (CCW) systems in nuclear power plants has been studied and documented as part of a research program sponsored by the US Nuclear Regulatory Commission. It was found that age related degradation leads to failures in the CCW system which can result in an increase in system unavailability, if not properly detected and mitigated. To identify effective methods of managing this degradation, information on inspection, monitoring, and maintenance practices currently available was obtained from various operating plants and reviewed. The findings were correlated with the most common aging mechanisms and failure modes and a compilation of aging detection and mitigation practices was formulated. This paper discusses the results of this work.
PurposeUsing a candidate-gene approach, a recent case-control study identified a previously unknown association between neovascular age-related macular degeneration (AMD) and the...Full Text Available
DOE-sponsored aging management guideline for electrical cable and terminators
1996-03-01
The DOE-sponsored Aging Management Guideline (AMG) for Electrical Cable and Terminations provides an analysis of the potential age-related degradation mechanisms and effects for low-voltage and medium-voltage extruded cables and associated terminations used in commercial nuclear power plants. The AMG examined historical industry failure data and correlated this with postulated aging mechanisms and effects. Existing and developmental testing and condition monitoring techniques were evaluated, as well as current industry practices, in order to assess whether all significant aging mechanisms/effects are being effectively managed. Results of the study indicate that some aging mechanisms and effects are not directly addressed by current industry maintenance and surveillance practices; however, empirical evidence indicates that low- and medium-voltage cable and terminations are in general very reliable. A limited number of nondestructive (or essentially nondestructive) techniques currently available are potentially useful for evaluating low-voltage cable condition; however, such techniques do not currently exist for monitoring medium-voltage cable. Troubleshooting or diagnostic techniques are available to identify certain types of degradation.
AGE-RELATED SUSCEPTIBILITY: A GENOMICS APPROACH.
By the year 2030 more than 70 million Americans will be over the age of 65. These older adults are a subpopulation that may have special susceptibility to toxic insult due to critical characteristics of their life-stage. Current EPA testing guidelines do not identify the elderl...
2009-10-01
The sense of smell deteriorates in normal aging, but the underling mechanisms are still elusive. Here we investigated age-related alterations in expression patterns of odorant receptor (OR) genes and...Full Text Available
Exercise-Induced Hormesis May Help Healthy Aging
Hormesis plays a critical role in producing some major benefits derived from physical exercise. However whether these known cellular mechanisms are applicable to ameliorate age-related deterioration...Full Text Available
AGE-RELATED EFFECTS OF TOLUENE ON THE MOTOR ACTIVITY OF BROWN NORWAY RATS.
Senescence raises many uncertainties regarding susceptibility to environmental exposures. Compromises in reserve and repair mechanisms, and alterations in metabolic capacity, may make the aging population more susceptible to environmental contaminants. Additionally, increased var...
BACKGROUND: To investigate the prevalence and angiographic appearances of polypoidal choroidal vasculopathy (PCV) masquerading as age-related peripapillary subretinal neovascular membranes (PSRNVM). METHODS: A consecutive case series of all patients investigated for presumed age-related PSRNVM in our tertiary referral centre over the period September 2006-2007. The presenting clinical features and fundus fluorescein angiographic (FFA) characteristics of each patient's lesion were identified. Any accompanying Indocyanine Green Angiogram (ICGA) was also reviewed, and on the basis of this investigation patients were classified into one of three groups: proven PCV, probable PCV and PSRNVM. RESULTS: Thirty patients with presumed age-related PSRNVM were identified. The FFA leakage pattern was occult in 21 patients and classic in nine patients. Sixteen patients also had ICGA performed. In 14 of these patients the original FFA leakage pattern was occult, and in two it was classic. Of the 14 patients with occult leakage on FFA who subsequently underwent ICGA all were found to have PCV. CONCLUSIONS: PCV is important and underrecognized in presumed age-related PSRNVMs. In such cases, particularly when the pattern of leakage on the fluorescein angiogram is occult, ICGA should be performed to identify the site of the polyps and if required to direct treatment.
Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration
2009-06-01
Full Text Available.PurposeTo describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD).MethodsWe retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval.ResultsFive patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10).ConclusionTachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.
Research Highlights from the Purdue-UAB Botanicals Research Center for Age Related Diseases
2009-08-01
Full Text Available.The Purdue-UAB Botanicals Research Center for Age Related Disease uses multidisciplinary and innovative technologies to investigate the bioavailability of bioactive polyphenolic constituents from botanicals and their relationship to human health. Many age-related diseases are associated with oxidative stress and tissue damage. One of the research goals of the Purdue-UAB Center is to investigate the bioavailability of bioactive natural compounds from a complex botanical mixture to the organ affected by the disease, determine the uptake and metabolism of these compounds and relate these data to a protective mechanism. Equally important is to screen commercially available botanicals for their safety and efficacy. The central aims of the Center include the investigation of botanicals and their relationship to bone antiresorptive capacity, cognitive function, vascular effects, and cancer prevention.
Genes encoding longevity: from model organisms to humans.
Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance and repair mechanisms that minimize age-related accumulation of permanent damage. Here, we describe the evolutionary conserved genes that are involved in lifespan regulation of model organisms and humans, and explore the reasons of discrepancies that exist between the results found in the various species. In general, the accumulated data have revealed that when moving up the evolutionary ladder, together with an increase of genome complexity, the impact of candidate genes on lifespan becomes smaller. The presence of genetic networks makes it more likely to expect impact of variation in several interacting genes to affect lifespan in humans. Extrapolation of findings from experimental models to humans is further complicated as phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar. Finally, currently used methodologies may have only little power and validity to reveal genetic variation in the population. In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain.
Age-related changes in functional connectivity of cerebellar PlV: a FDG PET study
2007-07-01
The cerebellum is known to have strong connection with cerebral cortex, and it shows the greatest mean shrinkage with aging. Changes in functional connectivity between cerebellum and cortical and subcortical cerebral areas possibly occur in normal aging. In this study, we tested changes of interregional connection between cerebellar posterior inferior vermis (PIV) and cerebrum in healthy subjects divided in three classes of age group (young: 20-30, middle age: 40-50, elderly: over 60 years) using FDG PET. 211 healthy subjects (age, 20-82 y; 134 female) were studied with resting-state brain glucose utilization measured by FDG-PET, cerebellar PIV activity after count-normalization to the whole gray matter mean count was extracted. Using PIV count as a 'seed', the maps of cross-correlation coefficients were computed by measuring the correlation between 'seed' and all the other brain voxels (P < 0.001 uncorrected, k = 100). Across all age groups, positive correlations of metabolic activity in the cerebellar PIV showed in cerebellum itself and bilateral thalamus. An extended positive correlation in cuneus which is served for visual information processing was observed in middle aged and elderly group differently from the young group. Also, in elderly group, this correlation was observed in the frontal areas such as right orbital and precentral gyri. Negative correlation implicating mutual inhibition between the areas was also founded in prefrontal and cingulate cortices and temporoparietal association areas. Comparing with the young group, in theses areas, enlarged negative correlations was founded with aging. We identified age related changes in cerebrocerebellar communication loop which reflect changes in local neuroplasticity in the normal aging brain. Present result may have implication for understanding the functional decline of cerebellum related cognitive ability as well as the deficit of motor coordination in normal aging and its compensation mechanism of brain.
Age-Related Degradation of Nuclear Power Plant Structures and Components
1999-03-29
This paper summarizes and highlights the results of the initial phase of a research project on the assessment of aged and degraded structures and components important to the safe operation of nuclear power plants (NPPs). A review of age-related degradation of structures and passive components at NPPs was performed. Instances of age-related degradation have been collected and reviewed. Data were collected from plant generated documents such as Licensing Event Reports, NRC generic communications, NUREGs and industry reports. Applicable cases of degradation occurrences were reviewed and then entered into a computerized database. The results obtained from the review of degradation occurrences are summarized and discussed. Various trending analyses were performed to identify which structures and components are most affected, whether degradation occurrences are worsening, and what was the most common aging mechanisms. The paper also discusses potential aging issues and degradation-susceptible structures and passive components which would have the greatest impact on plant risk.
Age-Related Degradation of Nuclear Power Plant Structures and Components
This paper summarizes and highlights the results of the initial phase of a research project on the assessment of aged and degraded structures and components important to the safe operation of nuclear power plants (NPPs). A review of age-related degradation of structures and passive components at NPPs was performed. Instances of age-related degradation have been collected and reviewed. Data were collected from plant generated documents such as Licensing Event Reports, NRC generic communications, NUREGs and industry reports. Applicable cases of degradation occurrences were reviewed and then entered into a computerized database. The results obtained from the review of degradation occurrences are summarized and discussed. Various trending analyses were performed to identify which structures and components are most affected, whether degradation occurrences are worsening, and what was the most common aging mechanisms. The paper also discusses potential aging issues and degradation-susceptible structures and passive components which would have the greatest impact on plant risk.
AGE-RELATED DEGRADATION OF NUCLEAR POWER PLANT STRUCTURES AND COMPONENTS.
This paper summarizes and highlights the results of the initial phase of a research project on the assessment of aged and degraded structures and components important to the safe operation of nuclear power plants (NPPs). A review of age-related degradation of structures and passive components at NPPs was performed. Instances of age-related degradation have been collected and reviewed. Data were collected from plant generated documents such as Licensing Event Reports, NRC generic communications, NUREGs and industry reports. Applicable cases of degradation occurrences were reviewed and then entered into a computerized database. The results obtained from the review of degradation occurrences are summarized and discussed. Various trending analyses were performed to identify which structures and components are most affected, whether degradation occurrences are worsening, and what are the most common aging mechanisms. The paper also discusses potential aging issues and degradation-susceptible structures and passive components which would have the greatest impact on plant risk.
AGE-RELATED DEGRADATION OF NUCLEAR POWER PLANT STRUCTURES AND COMPONENTS.
1999-03-29
This paper summarizes and highlights the results of the initial phase of a research project on the assessment of aged and degraded structures and components important to the safe operation of nuclear power plants (NPPs). A review of age-related degradation of structures and passive components at NPPs was performed. Instances of age-related degradation have been collected and reviewed. Data were collected from plant generated documents such as Licensing Event Reports, NRC generic communications, NUREGs and industry reports. Applicable cases of degradation occurrences were reviewed and then entered into a computerized database. The results obtained from the review of degradation occurrences are summarized and discussed. Various trending analyses were performed to identify which structures and components are most affected, whether degradation occurrences are worsening, and what are the most common aging mechanisms. The paper also discusses potential aging issues and degradation-susceptible structures and passive components which would have the greatest impact on plant risk.
Mechanisms of reproductive aging: conserved mechanisms and environmental factors
2010-01-01
The interplay of neuroendocrine processes and gonadal function is exquisitely expressed during aging. In females, loss of ovarian function results in decreased circulating estradiol. As a result, estrogen-dependent endocrine and behavioral responses decline, including impaired cognitive function reflecting the impact of declining estrogen on the hippocampus circuits, and decreased metabolic endocrine function. Concurrently, age-related changes in neuroendocrine response also contribute to the declining reproductive function. Our session considered key mechanisms in reproductive aging including the roles of ovarian function (Finch and Holmes) and the hypothalamic median eminence (Yin and Gore) with an associated age-related cognitive decline that accompanies estrogen loss (Morrison and coll...
Age-related crosslink in skin collagen
1986-01-01
A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and 1H, 13C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached ...
2010-01-01
As a fully differentiated organ, our brain is very sensitive to cumulative oxidative damage of proteins, lipids, and DNA occurring during normal aging because of its high energy metabolism and the relative low activity of antioxidative defense mechanisms. As a major consequence, perturbations of energy metabolism including mitochondrial dysfunction, alterations of signaling mechanisms and of gene expression culminate in functional deficits. With the increasing average life span of humans, age-related cognitive disorders such as Alzheimers disease (AD) are a major health concern in our society. Age-related mitochondrial dysfunction underlies most neurodegenerative diseases, where it is potentiated by disease-specific factors. AD is characterized by two major histopathological hallmarks, ...
Relating Imaging Indices of White Matter Integrity and Volume in Healthy Older Adults
2008-01-01
Age-related alterations in white matter have the potential to profoundly affect cognitive functioning. In fact, magnetic resonance imaging (MRI) studies using fractional anisotropy (FA) to measure white matter integrity reveal a positive correlation between FA and behavioral performance in older adults. Confounding these results are imaging studies demonstrating age-related white matter atrophy in some areas displaying altered FA, suggesting changes in diffusion may be simply an epiphenomenon of tissue loss. In the current study, structural MRI techniques were used to identify the relationship between white matter integrity and decreased volume in healthy aging adults. The data demonstrated that white matter atrophy did in fact account for differences in some areas, but significant FA decr...
2009-01-01
Exposure to heavy metals promotes oxidative stress and damage to cellular components, and may accelerate age-related disease and disability. Physical mobility is a validated biomarker of age-related disability and is predictive of hospitalization and mortality. Our study examined associations between selected heavy metals and impaired lower limb mobility in a representative older human population. Data for 1615 adults aged ≥60 yr from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 were used to identify associations between urinary concentrations of 10 metals with self-reported and measured significant walking impairments. Models were adjusted for confounding factors, including smoking. In models adjusted for age, gender, and ethnicity, elevated levels of ...
Current and future surveillance testing: WH atmosphere, HE and cellular silicone
1996-04-01
Selected surveillance data on warhead atmospheres, high explosives, and cellular silicone stress cushions will be presented for LLNL Enduring Stockpile weapons. Possible interpretations of apparent aging trends will be offered. Thoughts on additional surveillance testing that could enhance or ability to identify age related changes will be discussed.
PurposeIn a previous study, several quantitative trait loci (QTL) that influence age-related degeneration (ageRD) were identified in a cross between the albino strains B6(Cg)-Tyr(c-2J)/J...Full Text Available
NPAR- products, applications and closure
1995-01-01
Almost a decade ago the Office of Nuclear Regulatory Research (RES) developed and implemented a comprehensive research program (NUREG-1144) widely known as NPAR or Nuclear Plant Aging Research. The NPAR program is a structured research program specifically oriented to understanding significant age-related degradation mechanisms and their long term effects on properties and performance of important components and systems and ways to mitigate detrimental effects of aging. It provided a road map and a phased approach to research that is applicable to any structure, system, or component of interest. This hardware-oriented engineering research program led the industry worldwide and communicated a need to understand and manage age-related degradation effects in selected but important structures and components. At the conclusion (1995) of the NPAR program, 22 ...
2010-01-01
A body of research has demonstrated age-related slowing on tasks that emphasize cognitive control, such as task switching. However, little is known about the neural mechanisms that contribute to this age-related slowing. To address this issue, the present study used both fMRI and DTI in combination with a standard task switching paradigm. Results from the fMRI experiment demonstrated task switching cost (switching vs. nonswitching) activations in a network of frontoparietal and striatal regions in the young group. The older group recruited a similar network of regions, but showed decreased spatial extent of activation and recruited several regions not activated in the young group. White matter (WM) ROIs bordering the cortical network showing task switching activation were then selected to ...
2010-01-01
The Color Stroop Test is consensually considered as a task to assess the efficiency of inhibitory mechanisms. If the Stroop interference effect is largely undisputed, it is also acknowledged that the size of this effect varies as a function of various task manipulations, such as the task format. The aim of the present study was to compare the size of adult age-related differences in inhibition as assessed by two different versions of the Color Stroop Test: a standard Blocked paper-and-pencil version and a computerized Item-by-item one. Results showed pronounced age-related differences in the interference effect in the Blocked version, but not in the Item-by-item one. These findings are discussed in terms of the characteristics of the tasks. The choice of the appropriate version with respec...
Full Text Available.Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs) is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.
2010-06-01
A quantitative proteomics analysis of the macular Bruch membrane/choroid complex was pursued for insights into the molecular mechanisms of age-related macular degeneration (AMD). Protein in trephine...Full Text Available
BackgroundPlant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are...Full Text Available
BackgroundMitochondrial dysfunction and oxidative stress are central mechanisms underlying the aging process and the pathogenesis of many age-related diseases. Selected antioxidants...Full Text Available
Optimizing Dietary Restriction for Genetic Epistasis Analysis and Gene Discovery in C. elegans
Full Text Available.Dietary restriction (DR) increases mammalian lifespan and decreases susceptibility to many age-related diseases. Lifespan extension due to DR is conserved across a wide range of species. Recent research has focused upon genetically tractable model organisms such as C. elegans to uncover the genetic mechanisms that regulate the response to DR, in the hope that this information will provide insight into the mammalian response and yield potential therapeutic targets. However, no consensus exists as to the best protocol to apply DR to C. elegans and potential key regulators of DR are protocol-specific. Here we define a DR method that better fulfills criteria required for an invertebrate DR protocol to mirror mammalian studies. The food intake that maximizes longevity varies for different genotypes and informative epistasis analysis with another intervention is only achievable at this ‘optimal DR’ level. Importantly therefore, the degree of restriction imposed using our method can easily be adjusted to determine the genotype-specific optimum DR level. We used this protocol to test two previously identified master regulators of DR in the worm. In contrast to previous reports, we find that DR can robustly extend the lifespan of worms lacking the AMP-activated protein kinase catalytic subunit AAK2 or the histone deacetylase SIR-2.1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity.
Advanced Transmission Electron Microscopy of Pu Alloys
2003-01-27
The characterization of microstructural changes in Pu-Ga alloys resulting from storage and aging phenomena is an important technical challenge to the nuclear Stockpile Stewardship program. We have identified at least two age-related phenomena that may occur in Pu alloys, dimensional changes due to the initial transient, helium accumulation, and void swelling, and phase instability. The initial transient is a well-known effect that results from the initial cascade damage. This form of dimensional change tends to saturate within approximately two years. A second contributor to dimensional change is the build-up of helium as a result of the alpha decay. Helium is generated at a rate of approximately 40 parts per million per year. Positron annihilation results by Howell indicate that the helium atoms will quickly fill a nearby vacancy and diffuse through the lattice as a helium filled vacancy. Void swelling is potentially the most severe mechanism of dimensional change in Pu alloys. It has been observed in all-materials exposed to irradiation, but has yet to be seen in naturally aged Pu. Phase instability is a potential concern due to the fact that the {delta}-phase is thermodynamically metastable at room temperature. Timofeeva has shown that the {delta}-phase will decompose to {delta}-phase and Pu{sub 3}Ga given enough time at ambient temperature. At sub-ambient temperatures, the {delta}-phase undergoes a displacive or martensitic phase transformation to the monoclinic {alpha}{prime}-phase, which is approximately 20% more dense. Phase transformations such as these would result in density changes, dimensional changes, and Changes in mechanical properties. Traditional characterization techniques such as optical microscopy, x-ray diffraction and scanning electron microscopy are insensitive to many of the age-related microstructural changes. In this investigation, we have applied advanced transmission electron microscopy (TEM) to investigate the microstructure and bonding of Pu alloys. A 300 keV Phillips CM300FEG with a field emission gun electron source and Gatan Imaging Filter are used for the investigations.
PURPOSE: To report a neovascular age-related macular degeneration pattern refractory to ranibizumab. DESIGN: Retrospective, observational case series. METHODS: Between March and May 2009, cases with neovascular age-related macular degeneration refractory to ranibizumab were investigated with indocyanine green angiography. We identified 12 eyes of 12 patients with polypoidal choroidal vasculopathy. Refractory to treatment were defined cases with persistent subretinal or intraretinal fluid, or both, after 3 or more consecutive monthly ranibizumab injections regardless of best-corrected visual acuity. RESULTS: All patients identified were white, of whom 6 were male. Mean age +/- standard deviation at presentation was 75 +/- 5.6 years (range, 64 to 81 years); diagnosis, based on fluorescein angiography, comprised occult choroidal neovascularization (CNV) in 8 eyes, and 1 case each of classic-no-occult CNV, minimally classic CNV, predominantly classic CNV, and retinal angiomatous proliferation. Eight cases had switched from courses of other therapy (5 pegaptanib, 1 photodynamic therapy, 1 photodynamic therapy then pegaptanib, 1 bevacizumab). After a mean follow-up of 10.2 +/- 4.8 months (range, 3 to 18 months) and 7.6 +/- 3.9 ranibizumab injections (range, 3 to 14 injections), indocyanine green angiography revealed polypoidal choroidal vasculopathy lesions in all cases. CONCLUSIONS: Neovascular age-related macular degeneration refractory to a course of ranibizumab injections may harbor polypoidal choroidal vasculopathy. In such cases, indocyanine green angiography is a valuable tool for revealing polypoidal lesions.
Epigenetic factors in aging and longevity
2010-01-01
Epigenetics refers to phenotypic changes caused by mechanisms that are unrelated to changes in the underlying DNA sequence, most notably chromatin remodeling driven by histone modifications, and DNA methylation. Such variation is transmitted by cell division, but generally not passed on through the germ line. An increasing body of evidence supports a role for epigenetic changes in the etiology of aging and its associated disease sequelae. Here, we review the role of epigenetics in aging and longevity with a focus on DNA methylation. Increased understanding of those aging-related processes that are driven by epigenetic mechanisms will allow for the development of novel epigenetic-based diagnostic, preventive, and therapeutic strategies for age-related diseases.
Complexity of age-related change in skeletal muscle.
Age-related changes in skeletal muscle mass, fiber area, and contractile function were examined in pathogen-free rats at 6, 12, 28 and 36 mos of age. The intent of this study was to clarify age-related decline, particularly in contractile force, and to determine if the decline in contractile tension with age is due to alterations at the neuromuscular junction. A variable amount of age-associated reduction in muscle mass was noted for the soleus (18%), extensor digitorum longus (EDL-16%), plantaris (37%), and gastrocnemius (38%) muscles. The decline in fiber area for these four muscles was between 5 and 16% greater than the loss in muscle wet weight. A variable amount of change in peak contractile force between 6 and 36 mos was observed for the soleus (62%), EDL (48%), and plantaris (34%). For soleus and EDL, the decline in peak tetanic tension exceeded the decline in muscle mass and fiber area. Most of the declines for the animals used in this study did not become significant until after the age of 28 mo. The marked reduction in peak tetanic tension, fiber area, and muscle mass between 28 and 36 mos indicates an accelerated age-related decline in this time period. The reduced peak twitch and peak tetanic tension in the oldest animals was not due to likely age-related changes at the neuromuscular junction. Peak values for tetanic tension were similar, whether tension was elicited via direct muscle stimulation or through stimulation of the nerve. Results underscore the complexity of age-related change and suggest that multiple mechanisms contribute to the decline of skeletal muscle.
Role of Sirtuin Histone Deacetylase SIRT1 in Prostate Cancer
2009-02-06
Full Text Available.Prostate cancer (PCa) is a major age-related malignancy, and according to estimates from the American Cancer Society, a man's chance of developing this cancer significantly increases with increasing age, from 1 in 10,149 by age 39 to 1 in 38 by age 59 to 1 in 7 by age 70. Therefore, it is important to identify the causal connection between mechanisms of aging and PCa. Employing in vitro and in vivo approaches, in this study, we tested the hypothesis that SIRT1, which belongs to the Sir2 (silent information regulator 2) family of sirtuin class III histone deacetylases, is overexpressed in PCa, and its inhibition will have antiproliferative effects in human PCa cells. Our data demonstrated that SIRT1 was significantly overexpressed in human PCa cells (DU145, LNCaP, 22Rν1, and PC3) compared with normal prostate epithelial cells (PrEC) at protein, mRNA, and enzymatic activity levels. SIRT1 was also found to be overexpressed in human PCa tissues compared with adjacent normal prostate tissue. Interestingly, our data demonstrated that SIRT1 inhibition via nicotinamide and sirtinol (at the activity level) as well as via short hairpin RNA-mediated RNA interference (at the genetic level) resulted in a significant inhibition in the growth and viability of human PCa cells while having no effect on normal prostate epithelial cells. Further, we found that inhibition of SIRT1 caused an increase in FOXO1 acetylation and transcriptional activation in PCa cells. Our data suggested that SIRT1, via inhibiting FOXO1 activation, could contribute to the development of PCa. We suggest that SIRT1 could serve as a target toward developing novel strategies for PCa management.
2009-01-01
Full Text Available.BackgroundThe annual fish Nothobranchius furzeri is the vertebrate with the shortest known life span in captivity. Fish of the GRZ strain live only three to four months under optimal laboratory conditions, show explosive growth, early sexual maturation and age-dependent physiological and behavioral decline, and express aging related biomarkers. Treatment with resveratrol and low temperature significantly extends the maximum life span. These features make N. furzeri a promising new vertebrate model for age research.ResultsTo contribute to establishing N. furzeri as a new model organism, we provide a first insight into its genome and a comparison to medaka, stickleback, tetraodon and zebrafish. The N. furzeri genome contains 19 chromosomes (2n = 38). Its genome of between 1.6 and 1.9 Gb is the largest among the analyzed fish species and has, at 45%, the highest repeat content. Remarkably, tandem repeats comprise 21%, which is 4-12 times more than in the other four fish species. In addition, G+C-rich tandem repeats preferentially localize to centromeric regions. Phylogenetic analysis based on coding sequences identifies medaka as the closest relative. Genotyping of an initial set of 27 markers and multi-locus fingerprinting of one microsatellite provides the first molecular evidence that the GRZ strain is highly inbred.ConclusionsOur work presents a first basis for systematic genomic and genetic analyses aimed at understanding the mechanisms of life span determination in N. furzeri.
2005-03-01
The performance and reliability of microelectromechanical (MEMS) devices can be highly dependent on the control of the surface energetics in these structures. Examples of this sensitivity include the use of surface modifying chemistries to control stiction, to minimize friction and wear, and to preserve favorable electrical characteristics in surface micromachined structures. Silane modification of surfaces is one classic approach to controlling stiction in Si-based devices. The time-dependent efficacy of this modifying treatment has traditionally been evaluated by studying the impact of accelerated aging on device performance and conducting subsequent failure analysis. Our interest has been in identifying aging related chemical signatures that represent the early stages of processes like silane displacement or chemical modification that eventually lead to device performance changes. We employ a series of classic surface characterization techniques along with multivariate statistical methods to study subtle changes in the silanized silicon surface and relate these to degradation mechanisms. Examples include the use of spatially resolved time-of-flight secondary ion mass spectrometric, photoelectron spectroscopic, photoluminescence imaging, and scanning probe microscopic techniques to explore the penetration of water through a silane monolayer, the incorporation of contaminant species into a silane monolayer, and local displacement of silane molecules from the Si surface. We have applied this analytical methodology at the Si coupon level up to MEMS devices. This approach can be generalized to other chemical systems to address issues of new materials integration into micro- and nano-scale systems.
Boiling-Water Reactor internals aging degradation study. Phase 1
This report documents the results of an aging assessment study for boiling water reactor (BWR) internals. Major stressors for BWR internals are related to unsteady hydrodynamic forces generated by the primary coolant flow in the reactor vessel. Welding and cold-working, dissolved oxygen and impurities in the coolant, applied loads and exposures to fast neutron fluxes are other important stressors. Based on results of a component failure information survey, stress corrosion cracking (SCC) and fatigue are identified as the two major aging-related degradation mechanisms for BWR internals. Significant reported failures include SCC in jet-pump holddown beams, in-core neutron flux monitor dry tubes and core spray spargers. Fatigue failures were detected in feedwater spargers. The implementation of a plant Hydrogen Water Chemistry (HWC) program is considered as a promising method for controlling SCC problems in BWR. More operating data are needed to evaluate its effectiveness for internal components. Long-term fast neutron irradiation effects and high-cycle fatigue in a corrosive environment are uncertainty factors in the aging assessment process. BWR internals are examined by visual inspections and the method is access limited. The presence of a large water gap and an absence of ex-core neutron flux monitors may handicap the use of advanced inspection methods, such as neutron noise vibration measurements, for BWR.
Boiling-Water Reactor internals aging degradation study. Phase 1
This report documents the results of an aging assessment study for boiling water reactor (BWR) internals. Major stressors for BWR internals are related to unsteady hydrodynamic forces generated by the primary coolant flow in the reactor vessel. Welding and cold-working, dissolved oxygen and impurities in the coolant, applied loads and exposures to fast neutron fluxes are other important stressors. Based on results of a component failure information survey, stress corrosion cracking (SCC) and fatigue are identified as the two major aging-related degradation mechanisms for BWR internals. Significant reported failures include SCC in jet-pump holddown beams, in-core neutron flux monitor dry tubes and core spray spargers. Fatigue failures were detected in feedwater spargers. The implementation of a plant Hydrogen Water Chemistry (HWC) program is considered as a promising method for controlling SCC problems in BWR. More operating data are needed to evaluate its effectiveness for internal components. Long-term fast neutron irradiation effects and high-cycle fatigue in a corrosive environment are uncertainty factors in the aging assessment process. BWR internals are examined by visual inspections and the method is access limited. The presence of a large water gap and an absence of ex-core neutron flux monitors may handicap the use of advanced inspection methods, such as neutron noise vibration measurements, for BWR.
Boiling-Water Reactor internals aging degradation study. Phase 1
1993-09-01
This report documents the results of an aging assessment study for boiling water reactor (BWR) internals. Major stressors for BWR internals are related to unsteady hydrodynamic forces generated by the primary coolant flow in the reactor vessel. Welding and cold-working, dissolved oxygen and impurities in the coolant, applied loads and exposures to fast neutron fluxes are other important stressors. Based on results of a component failure information survey, stress corrosion cracking (SCC) and fatigue are identified as the two major aging-related degradation mechanisms for BWR internals. Significant reported failures include SCC in jet-pump holddown beams, in-core neutron flux monitor dry tubes and core spray spargers. Fatigue failures were detected in feedwater spargers. The implementation of a plant Hydrogen Water Chemistry (HWC) program is considered as a promising method for controlling SCC problems in BWR. More operating data are needed to evaluate its effectiveness for internal components. Long-term fast neutron irradiation effects and high-cycle fatigue in a corrosive environment are uncertainty factors in the aging assessment process. BWR internals are examined by visual inspections and the method is access limited. The presence of a large water gap and an absence of ex-core neutron flux monitors may handicap the use of advanced inspection methods, such as neutron noise vibration measurements, for BWR.
Age-related crosslink in skin collagen
A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.
Age-related crosslink in skin collagen
1986-05-01
A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.
Pressurized-water reactor internals aging degradation study. Phase 1
This report documents the results of a Phase I study on the effects of aging degradations on pr internals. Primary stressers for internals an generated by the primary coolant flow in the they include unsteady hydrodynamic forces and pump-generated pressure pulsations. Other stressors are applied loads, manufacturing processes, impurities in the coolant and exposures to fast neutron fluxes. A survey of reported aging-related failure information indicates that fatigue, stress corrosion cracking (SCC) and mechanical wear are the three major aging-related degradation mechanisms for PWR internals. Significant reported failures include thermal shield flow-induced vibration problems, SCC in guide tube support pins and core support structure bolts, fatigue-induced core baffle water-jet impingement problems and excess wear in flux thimbles. Many of the reported problems have been resolved by accepted engineering practices. Uncertainties remain in the assessment of long-term neutron irradiation effects and environmental factors in high-cycle fatigue failures. Reactor internals are examined by visual inspections and the technique is access limited. Improved inspection methods, especially one with an early failure detection capability, can enhance the safety and efficiency of reactor operations.
Pressurized-water reactor internals aging degradation study. Phase 1
This report documents the results of a Phase I study on the effects of aging degradations on pr internals. Primary stressers for internals an generated by the primary coolant flow in the they include unsteady hydrodynamic forces and pump-generated pressure pulsations. Other stressors are applied loads, manufacturing processes, impurities in the coolant and exposures to fast neutron fluxes. A survey of reported aging-related failure information indicates that fatigue, stress corrosion cracking (SCC) and mechanical wear are the three major aging-related degradation mechanisms for PWR internals. Significant reported failures include thermal shield flow-induced vibration problems, SCC in guide tube support pins and core support structure bolts, fatigue-induced core baffle water-jet impingement problems and excess wear in flux thimbles. Many of the reported problems have been resolved by accepted engineering practices. Uncertainties remain in the assessment of long-term neutron irradiation effects and environmental factors in high-cycle fatigue failures. Reactor internals are examined by visual inspections and the technique is access limited. Improved inspection methods, especially one with an early failure detection capability, can enhance the safety and efficiency of reactor operations.
Pressurized-water reactor internals aging degradation study. Phase 1
1993-09-01
This report documents the results of a Phase I study on the effects of aging degradations on pr internals. Primary stressers for internals an generated by the primary coolant flow in the they include unsteady hydrodynamic forces and pump-generated pressure pulsations. Other stressors are applied loads, manufacturing processes, impurities in the coolant and exposures to fast neutron fluxes. A survey of reported aging-related failure information indicates that fatigue, stress corrosion cracking (SCC) and mechanical wear are the three major aging-related degradation mechanisms for PWR internals. Significant reported failures include thermal shield flow-induced vibration problems, SCC in guide tube support pins and core support structure bolts, fatigue-induced core baffle water-jet impingement problems and excess wear in flux thimbles. Many of the reported problems have been resolved by accepted engineering practices. Uncertainties remain in the assessment of long-term neutron irradiation effects and environmental factors in high-cycle fatigue failures. Reactor internals are examined by visual inspections and the technique is access limited. Improved inspection methods, especially one with an early failure detection capability, can enhance the safety and efficiency of reactor operations.
Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys.
Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is the most frequently occurring sensory disorder in the elderly population. AHL is characterized by a decline of auditory function and loss of hair cells and spiral ganglion neurons in the cochlea of the inner ear. It has been postulated that AHL occurs gradually as a result of the cumulative effect with aging of exposure to noise, diet, oxidative damage, and mitochondrial DNA mutations. However, the molecular mechanisms of AHL remain unclear and no preventative or therapeutic interventions have been developed. A growing body of evidence suggests increased oxidative damage with aging to macromolecules such as DNA, proteins, and lipids may play a causal role in aging and age-related diseases. Caloric restriction (CR) extends the lifespan of most mammalian species, delays the onset of multiple age-related diseases, and attenuates both the degree of oxidative damage and the associated decline in physiological function. Here, we review studies on CR's ability to prevent cochlear pathology and AHL in laboratory animals and discuss potential molecular mechanisms of CR's actions.
2010-01-01
We reply to criticisms by Penke and Deary (2010) of our model relating loss of white matter integrity in normal aging to cognitive change. We identify difficulties in their alternative path analysis in which they attempt to relate age-related loss of integrity of white matter to changes in general intelligence. We then comment on their general criticisms and their viewpoints concerning use of path analysis.
Medikamenten-induzierte Delirien lterer Menschen
2010-01-01
Summary Drugs have been widely associated with the development of delirium in the elderly and represent the most common reversible cause of this condition. This is of importance since successful treatment depends on identifying the reversible contributing factors. Medications with anticholinergic properties, tranquilizers, analgesics and narcotics are common causes of drug-induced delirium. This article provides practical approach to prevent and recognise this condition, reviews the underlying neurotransmitter imbalances and reconsiders age-related changes of pharmacological effects, which may contribute to the development of delirium.
2010-01-01
Full Text Available.A central goal of biogerontology is to identify robust gene-expression biomarkers of aging. Here we develop a method where the biomarkers are networks of genes selected based on age-dependent activity and a graph-theoretic property called modularity. Tested on Caenorhabditis elegans, our algorithm yields better biomarkers than previous methods - they are more conserved across studies and better predictors of age. We apply these modular biomarkers to assign novel aging-related functions to poorly characterized longevity genes.
Nondestructive analysis of Au-Cr layers in aged microcircuits
1997-11-01
Particle-induced x-ray emission (PIXE), Rutherford backscattering spectroscopy (RBS), and nuclear reaction analysis (NRA) are being used to investigated compositional changes in MK4 radar unit microelectronics resulting from possible age-related chromium diffusion in gold. Since the analysis is nondestructive, changes in the mechanical properties of the system can be more readily correlated to measured compositional changes at the buried interface. Measurements are conducted to investigate trace levels of chromium at the external Au surface, determine the actual gold layer thickness of the test sample, and measure compositional changes occurring at the Au-Cr interface.
Mitochondrial dysfunction and intracellular calcium dysregulation in ALS
2010-01-01
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that affects the aging population. A progressive loss of motor neurons in the spinal cord and brain leads to muscle paralysis and death. As in other common neurodegenerative diseases, aging-related mitochondrial dysfunction is increasingly being considered among the pathogenic factors. Mitochondria are critical for cell survival: they provide energy to the cell, buffer intracellular calcium, and regulate apoptotic cell death. Whether mitochondrial abnormalities are a trigger or a consequence of the neurodegenerative process and the mechanisms whereby mitochondrial dysfunction contributes to disease are not clear yet. Calcium homeostasis is a major function of mitochondria in neurons, and there is ample evidence...
The health safety and health promotion needs of older workers
2010-01-01
Aims To evaluate current research on the health, safety and health promotion needs of older workers by identifying age-related change, whether older workers need support and evidence of successful intervention in the workplace. Methods Using a systematic review methodology, databases were searched identifying 180 publications. Each publication was reviewed and data were extracted. Evidence was assessed for quality using the three-star system. Results The review identified that there are a number of age-related physical and psychological changes. However, these changes can be moderated by increased physical activity, intellectual activity and other lifestyle factors. Sensory abilities are also subject to change but some of these can be accommodated via equipment or workplace adjustments. In...
2009-01-01
The Korea Atomic Energy Research Institute (KAERI) and Brookhaven National Laboratory (BNL) are collaborating to develop seismic capability evaluation technology for degraded structures and passive components (SPCs) under a multi-year research agreement. To better understand the status and characteristics of degradation of SPCs in nuclear power plants (NPPs), the first step in this multi-year research effort was to identify and evaluate degradation occurrences of SPCs in U.S. NPPs. This was performed by reviewing recent publicly available information sources to identify and evaluate the characteristics of degradation occurrences and then comparing the information to the observations in the past. Ten categories of SPCs that are applicable to Korean NPPs were identified, comprising of anchorage, concrete, containment, exchanger, filter, piping system, reactor ...
2009-01-01
Objective To evaluate the impact of statin use on the incidence of advanced age-related macular degeneration (AMD) and its components, choroidal neovascularization (CNV) and geographic atrophy (GA), among patients with bilateral large drusen. Design Cohort study within a multicenter, randomized, clinical trial. Participants Patients enrolled in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Methods Eligibility criteria for the clinical trial required that participants have ≥10 large (>125 μm) drusen and visual acuity ≥20/40 in each eye. Patients scheduled for their final CAPT visit after May 2005 were interviewed on their history of use of cholesterol-lowering medications, including statins. Trained readers identified CNV and end ...
Highly eusocial insect workers exhibit age-related division of labor. Adults begin working inside the nest, moving to the nest periphery and later to foraging. Passage through this task sequence is associated with neuroanatomical changes in the mushroom bodies (MB) of honey bee (Apis) and ant (Camponotus) workers. We asked whether eusocial wasp workers (Polybia aequatorialis) exhibit similar changes in adult neuroanatomy. Wasps were identified as working in-nest, on-nest, or foraging. The volumes of the somata of workers' MB intrinsic neurons (Kenyon cells), and of the neuropils containing the Kenyon cell dendritic arbors (calyces), were estimated using stereological methods. In-nest workers had significantly smaller calyx to Kenyon cell volume ratios than on-nest and foraging workers. Age-related task specializations in Polybia workers are associated with major neuroanatomical reorganization in the mushroom bodies.
Adult age differences in functional connectivity during executive control
2010-01-01
Task switching requires executive control processes that undergo age-related decline. Previous neuroimaging studies have identified age-related differences in brain activation associated with global switching effects (dual-task blocks versus single-task blocks), but age-related differences in activation during local switching effects (switch trials versus repeat trials, within blocks) have not been investigated. This experiment used functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI), to examine adult age differences in task switching across adjacent trials (i.e., local task switching). During fMRI scanning, participants performed a cued, word categorization task. From interspersed cue-only trials, switch-related processing associated with the cue was estimated...
BACKGROUND: Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to increasing knowledge of the immunological mechanisms associated with anti-malarial protection, will help in the development of malaria vaccines. METHODS AND FINDINGS: We conducted a 1-year follow-up study of 305 Senegalese children and identified those resistant or susceptible to malaria. In retrospective analyses we then compared post-follow-up IgG responses to six asexual-stage candidate malaria vaccine antigens in groups of individuals with clearly defined clinical and parasitological histories of infection with P. falciparum. In age-adjusted analyses, children resistant to malaria as well as to high-density parasitemia, had significantly higher IgG1 responses to GLURP and IgG3 responses to MSP2 than their susceptible counterparts. Among those resistant to malaria, high anti-MSP1 IgG1 levels were associated with protection against high-density parasitemia. To assess functional attributes, we used an in vitro parasite growth inhibition assay with purified IgG. Samples from individuals with high levels of IgG directed to MSP1, MSP2 and AMA1 gave the strongest parasite growth inhibition, but a marked age-related decline was observed in these effects. CONCLUSION: Our data are consistent with the idea that protection against P. falciparum malaria in children depends on acquisition of a constellation of appropriate, functionally active IgG subclass responses directed to multiple asexual stage antigens. Our results suggest at least two distinct mechanisms via which antibodies may exert protective effects. Although declining with age, the growth inhibitory effects of purified IgG measurable in vitro reflected levels of anti-AMA1, -MSP1 and -MSP2, but not of anti-GLURP IgG. The latter could act on parasite growth via indirect parasiticidal pathways.
BACKGROUND: The maintenance of balance while standing is ensured by means of a sensory motor control system. As the development of sensory organization on posture control in children is not clear at this time, the aim of this study was to analyse the significance of each sensory component in relation to age and sex. SUBJECTS AND METHOD: A total of 128 children between the ages of 3 and 16 years and 23 adults were examined using the Sensory Organization Test (EquiTest). RESULTS: Age-related changes during the test procedure showed a developmental tendency of the sensory motor process. The influence of the proprioceptive function on stance stability seemed to be completely developed between 3-4 years. The visual and vestibular afferences reached the adult level between 15-16 years with differences between girls and boys. CONCLUSION: Age-related evaluation of the postural mechanisms can be used for differentiation between physiological and pathological results in balance control as well as for monitoring therapy progress in the context of, for example, hyperactivity or learning disability.
Age-related changes in grey and white matter structure throughout adulthood
2010-07-01
Full Text Available.AbstractNormal ageing is associated with gradual brain atrophy. Determining spatial and temporal patterns of change can help shed light on underlying mechanisms. Neuroimaging provides various measures of brain structure that can be used to assess such age-related change but studies to date have typically considered single imaging measures. Although there is consensus on the notion that brain structure deteriorates with age, evidence on the precise time course and spatial distribution of changes is mixed. We assessed grey matter (GM) and white matter (WM) structure in a group of 66 adults aged between 23 and 81. Multimodal imaging measures included voxel-based morphometry (VBM)-style analysis of GM and WM volume and diffusion tensor imaging (DTI) metrics of WM microstructure. We found widespread reductions in GM volume from middle age onwards but earlier reductions in GM were detected in frontal cortex. Widespread age-related deterioration in WM microstructure was detected from young adulthood onwards. WM decline was detected earlier and more sensitively using DTI-based measures of microstructure than using markers of WM volume derived from conventional T1-weighted imaging.
A Review of Information for Managing Aging in Nuclear Power Plants
Age related degradation effects in safety related systems of nuclear power plants should be managed to prevent safety margins from eroding below the acceptable limits provided in plant design bases. The Nuclear Plant Aging Research (NPAR) Pro- gram, conducted under the auspices of the U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, and other related aging management programs are developing technical information on managing aging. The aging management process central to these efforts consists of three key elements: 1) selecting structures, systems, and components (SSCs) in which aging should be controlled; 2) understanding the mechanisms and rates of degradation in these SSCs; and 3) managing degradation through effective inspection, surveillance, condition monitoring, trending, record keeping, mainten- ance, refurbishment, replacement, and adjustments in the operating environment and service conditions. This document concisely reviews and integrates information developed under the NPAR Program and other aging management studies and other available information related to understanding and managing age-related degradation effects and provides specific refer- ences to more comprehensive information on the same subjects.
A Review of Information for Managing Aging in Nuclear Power Plants
1995-09-01
Age related degradation effects in safety related systems of nuclear power plants should be managed to prevent safety margins from eroding below the acceptable limits provided in plant design bases. The Nuclear Plant Aging Research (NPAR) Pro- gram, conducted under the auspices of the U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, and other related aging management programs are developing technical information on managing aging. The aging management process central to these efforts consists of three key elements: 1) selecting structures, systems, and components (SSCs) in which aging should be controlled; 2) understanding the mechanisms and rates of degradation in these SSCs; and 3) managing degradation through effective inspection, surveillance, condition monitoring, trending, record keeping, mainten- ance, refurbishment, replacement, and adjustments in the operating environment and service conditions. This document concisely reviews and integrates information developed under the NPAR Program and other aging management studies and other available information related to understanding and managing age-related degradation effects and provides specific refer- ences to more comprehensive information on the same subjects.
An Epigenetic Hypothesis of Aging-Related Cognitive Dysfunction
Full Text Available.This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.
Use of `sham' radiotherapy in randomized clinical trials
2008-01-01
Summary The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macul...
Use of 'sham' radiotherapy in randomized clinical trials
2008-01-01
The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the ...
Skeletal Microdamage: Less About Biomechanics and More About Remodeling
2008-01-01
The mechanical consequences of skeletal microdamage have been clearly documented using various experimental methods, yet recent experiments suggest that physiological levels of microdamage accumulation are not sufficient to compromise the bones biomechanical properties. While great advances have been made in our understanding of the biomechanical implications of microdamage, less is known concerning the physiological role of microdamage in bone remodeling. Microdamage has been shown to act as a signal for bone remodeling, likely through a disruption of the osteocyte-canalicular network. Interestingly, age-related increases in microdamage are not accompanied by increases in bone remodeling suggesting that the physiological mechanisms which link microdamage and remodeling are compromised ...
Mitochondrial oxidative damage and apoptosis in age-related hearing loss
2010-01-01
Age-related hearing loss (AHL) is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. Experimental evidence suggests that mitochondrial dysfunction associated with reactive oxygen species (ROS) plays a central role in the aging process of cochlear cells. Although it is well established that mitochondria are the major source of ROS in the cell, specific molecular mechanisms of aging induced by ROS remain poorly characterized. Here we review the evidence that supports a central role for Bak-mediated mitochondrial apoptosis in AHL. We also propose that this mechanism may be of general relevance to age-related cell death in long-lived post-mitotic cells of multiple tissues, providing an opportunity for a targeted therapeutic intervention in...
Age-Related Changes in the Morphology and Mechanics of Arterial Wall in the Rat
This study was done to know the effects of aging on arterial mechanics from the viewpoint of tissue remodeling. Rats at growing (8 and 16weeks), maturated (32weeks) and middle (64weeks) ages were used. After blood pressure and blood flow were measured in the abdominal aorta and common carotid artery, respectively, the carotid artery was excised to obtain pressure-diameter relations and wall dimensions. Although blood pressure increased during growth and blood flow gradually increased with age, wall hoop stress and wall shear stress showed no significant changes except for a decrease in wall shear stress during growth, which was attributable to morphological changes of wall. Wall stiffness and elastic properties at in vivo pressure did not significantly change until maturation; however, they increased by middle age.
Full Text Available.BackgroundIn this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps.ResultsBehavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R
Age-related change of technetium-99m-HMDP distribution in the skeleton
To understand age-related changes of whole-body and regional skeletal metabolism, it is important to investigate the mechanisms of age-related bone loss and to develop suitable treatments for it. Bone biopsies show metabolism of the particular site examined while biochemical markers for bone metabolism reflect total skeletal metabolis. Bone scintigraphy is a convenient and simple way to analyze whole-body and regional skeletal metabolism. We attempted to study and understand age-related changes in bone metabolism by quantifying the bone scan and correlating it with biochemical bone metabolic markers. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution pattern were studied in men and women by bone scintigraphy using {sup 99m}Tc-hydroxy-methane-diphosphonate (HMDP). Bone scans were performed using a standard protocol and quantified by setting regions of interest (ROIs) on selected regions. WBSU and the skeletal distribution pattern were compared with simultaneously obtained serum biochemical markers. WBSU showed an increase with age in both sexes, but in women, uptake in the head and legs increased more relatively than in the thoracic region, while in men no such tendency was observed. Increase of WBSU and relative increase of uptakes in the head demonstrated a weak correlation with the serum levels of alkaline phosphatase and type 1 collagen metabolites. These results show an age-related increase of skeletal turnover and sex-dependent regional skeletal metabolism. The age-related changes seen in bone scintigrams might be a sign of progressive bone loss, reflecting changes in local bone matabolism. 23 refs., 3 figs., 1 tab.
Age-related change of technetium-99m-HMDP distribution in the skeleton
1996-05-01
To understand age-related changes of whole-body and regional skeletal metabolism, it is important to investigate the mechanisms of age-related bone loss and to develop suitable treatments for it. Bone biopsies show metabolism of the particular site examined while biochemical markers for bone metabolism reflect total skeletal metabolis. Bone scintigraphy is a convenient and simple way to analyze whole-body and regional skeletal metabolism. We attempted to study and understand age-related changes in bone metabolism by quantifying the bone scan and correlating it with biochemical bone metabolic markers. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution pattern were studied in men and women by bone scintigraphy using {sup 99m}Tc-hydroxy-methane-diphosphonate (HMDP). Bone scans were performed using a standard protocol and quantified by setting regions of interest (ROIs) on selected regions. WBSU and the skeletal distribution pattern were compared with simultaneously obtained serum biochemical markers. WBSU showed an increase with age in both sexes, but in women, uptake in the head and legs increased more relatively than in the thoracic region, while in men no such tendency was observed. Increase of WBSU and relative increase of uptakes in the head demonstrated a weak correlation with the serum levels of alkaline phosphatase and type 1 collagen metabolites. These results show an age-related increase of skeletal turnover and sex-dependent regional skeletal metabolism. The age-related changes seen in bone scintigrams might be a sign of progressive bone loss, reflecting changes in local bone matabolism. 23 refs., 3 figs., 1 tab.
2007-01-01
Chlorpyrifos and diazinon are two commonly used organophosphorus (OP) insecticides, and their primary mechanism of action involves the inhibition of acetylcholinesterase (AChE) by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) by estimating the bimolecular inhibitory rate constant (ki) values for CPO and DZO. Brain ChE inhibition and ki values following CPO and DZO incubation with neonatal Sprague-Dawley rats rat brain homogenates were determined at post natal day (PND) -5, -12 and -17 and compared with the corresponding inhibition and ki values obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. Chlorpyrifos-oxon resulted in greater ChE inhibition than DZO consistent with the estimated ki values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, where the order of ChE inhibition was PND-5 > PND-7 > PND-17 with ki values of 0.95, 0.50 and 0.22 nM-1hr-1, respectively. In contrast, DZO did not exhibit an age-related inhibition of neonatal brain ChE, and the estimated ki value at all PND ages was 0.02 nM-1hr-1. These results demonstrated an age- and chemical-related OP-selective inhibition of rat brain ChE which may be critically important in understanding the potential sensitivity of juvenile humans to specific OP exposures.
2002-01-01
Aging is associated with learning deficits and a decrease in neuronal excitability, reflected by an enhanced post-burst afterhyperpolarization (AHP), in CA1 hippocampal pyramidal neurons. To identify the current(s) underlying the AHP altered in aging neurons, whole-cell voltage-clamp recording experiments were performed in hippocampal slices from young and aging rabbits. Similar to previous reports, aging neurons were found to rest at more hyperpolarized potentials and have larger AHPs than young neurons. Given that compounds that reduce the slow outward calcium-activated potassium current (sI(AHP)), a major constituent of the AHP, also facilitate learning in aging animals, the sI(AHP) was pharmacologically isolated and characterized. Aging neurons were found to have an enhanced sI(AHP), the amplitude of which was significantly correlated to the amplitude of the AHP (r = 0.63; p < 0.001). Thus, an enhanced sI(AHP) contributes to the enhanced AHP in aging. No differences were found in the membrane resistance, capacitance, or kinetic and voltage-dependent properties of the sI(AHP). Because enhanced AHP in aging neurons has been hypothesized to be secondary to an enhanced Ca2+ influx via the voltage-gated L-type Ca2+ channels, we further examined the sI(AHP) in the presence of an L-type Ca2+ channel blocker, nimodipine (10 μM). Nimodipine caused quantitatively greater reductions in the sIAHP in aging neurons than in young neurons; however, the residual sIAHP was still significantly larger in aging neurons than in young neurons. Our data, in conjunction with previous studies showing a correlation between the AHP and learning, suggest that the enhancement of the sIAHP in aging is a mechanism that contributes to age-related learning deficits. Publisher: Soc Neuroscience Coverage: 2002-01-01T00:00:00Z
2009-01-01
Purpose The objective of this study was to compare the reasons why mothers do or do not have their adolescent daughters vaccinated against HPV. Methods Mothers of vaccinated and unvaccinated 11- to 17-year-old girls seen during preventive care visits in outpatient family medicine or pediatric clinics underwent an audiotaped structured telephone interview that used open-ended questions to assess the reasons underlying maternal decisions about HPV vaccination. Qualitative methods categorized maternal responses into themes. Results Interviews of 52 mothers (19 declining vaccination, 33 accepting) identified several distinct factors underlying their decisions about HPV vaccination. Lack of knowledge about HPV, age-related concerns, and low perceived risk of infection were commonly cited reason...
2010-01-01
Hundreds of genes and miRNAs have been identified as being involved in the determination of longevity, aging patterns and in the development of age-related diseases (ARDs). The interplay between these genes as well as the role of miRNAs in the context of proteinprotein interaction networks has as yet been poorly addressed. This work was undertaken in order to integrate the data accumulated in the field, from a network-based perspective. The results are organized in the NetAge databasean online database and network analysis tools for biogerontological research ( External Reference Not Shown ). The NetAge database contains gene sets and miRNA-regulated PPI networks for longevity, ARDs and aging-associated processes, and also common signatures (overlapping networks). The database is ava...
Survey on organic components in NPPs
1999-01-01
Within the mandate of the Principal Working Group 3 of the OECD/Nuclear Energy Agency (PWG-3) specific attention is given to ageing related effects. Ageing of nuclear power plant systems, structures or components may reduce, if unmitigated, the safety margins provided in the design. With respect to the functional capability of systems, structures or components, the problems are very complex and multifaceted. Significant efforts have been undertaken in several countries and international organisations to study the influence of ageing phenomena. There is a further need for an assessment of approaches taken to ageing issues, aimed at developing and reviewing general principles, promoting technical consensus and identifying areas where further work is required. At the 19. meeting of the PWG-3 in April 1996, a decision was made to examine the ageing of organic materials in ...
Standard Tool for Quantification in Health Impact Assessment:A Review
2010-01-01
Background The health impact assessment (HIA) of policy proposals is becoming common practice. HIA represents a broad approach with quantification of the impact of policy options at its core. However, no standard tool is available and it remains unclear whether any current model can serve as a standard for the field. Purpose The aim of this study is to assess whether already existing models can be used as a standard tool for the quantification step in an HIA. Methods A search in 2008 identified 20 models for HIA, of which six are sufficiently generic to allow for various and multiple diseases and different risk factors: Age-Related Morbidity and Death Analysis, Global Burden of Disease, Population Health Modeling, PREVENT, Proportional Life Table Method, and the National Institute for Publ...
2010-01-01
Objective: Quantitative measures are needed to identify diabetic patients at higher risk for CV events. Cell-derived microparticles (MPs) are submicron membrane vesicles released from activated cells that are indicative of cell damage. Progenitor cells (PCs) including proangiogenic cells (PACs), often termed endothelial progenitor cells (EPCs), are mediators of reparative capacity. We examined whether the relationship of MPs to PCs/PACs could be used as an improved and clinically feasible index of vascular pathology. Methods and Results: Plasma samples were collected from patients with early-stage (ES, Diagnosis 5 years,) Type 2 diabetes and compared with age related healthy subjects (H). PC and MP subtypes were measured by a combination of flow cyto...
Older home nursing patients' perception of social provisions and received care
2010-01-01
Scand J Caring Sci; 2010; 24; 523-532Older home nursing patients' perception of social provisions and received care Social loneliness and isolation may be some of the consequences that older people experience regarding age-related changes and losses, and nurses should be engaged in identifying social networks and social needs in this group. The aims of this study were to describe perceived social provisions in a group of older home-dwelling care-dependent patients, and to explore the relationship between perceived social provisions, physical functioning, mental state and reception of formal and informal care. The sample consisted of 242 persons aged 75+ years from seven municipalities in southern Norway, all receiving home nursing. Data were collected by means of structured interviews. Soc...
Neuroeconomics and aging: neuromodulation of economic decision making in old age.
Economic decision making is a complex process of integrating and comparing various aspects of economically relevant choice options. Neuroeconomics has made important progress in grounding these aspects of decision making in neural systems and the neurotransmitters therein. The dopaminergic and serotoninergic brain systems have been identified as key neurotransmitter systems involved in economic behavior. Both are known to be prone to significant changes during the adult lifespan. Similarly, economic behavior undergoes significant age-related changes over the course of the adult lifespan. Here we propose a triadic relationship between (a) economic decision making, (b) dopaminergic and serotonergic neuromodulation, and (c) aging. In this review, we describe the different relationships around this triad in detail and summarize current evidence that supports them. Based on the reviewed evidence, we propose new research agendas that take the entire triad into account.
2009-01-01
Background Age-related hip fractures are associated with poor functional outcomes, resulting in substantial personal and societal burden. There is a need to better identify reversible etiologic predictors of suboptimal functional recovery in this group. Methods The Sarcopenia and Hip Fracture (SHIP) study was a 5-year prospective cohort study following community-dwelling older persons admitted to three Sydney hospitals for hip fracture. Information was collected at baseline, and 4 and 12 months, including health status, quality of life, nutritional status, body composition, muscle strength, range of motion, gait velocity, balance, walking endurance, disability, cognition, depression, fear of falling, self-efficacy, social support, physical activity level, vision, and fall-related data, wit...
Memory Encoding and Dopamine in the Aging Brain: A Psychopharmacological Neuroimaging Study
2010-01-01
Normal aging brings with it changes in dopaminergic and memory functions. However, little is known about how these 2 changes are related. In this study, we identify a link between dopamine, episodic memory networks, and aging, using pharmacological functional magnetic resonance imaging. Young and older adults received a D2-like agonist (Bromocriptine, 1.25 mg), a D2-like antagonist (Sulpiride, 400 mg), and Placebo, in a double-blind crossover procedure. We observed group differences, during memory encoding, in medial temporal, frontal, and striatal regions and moreover, these regions were differentially sensitive across groups to dopaminergic perturbation. These findings suggest that brain systems underlying memory show age-related changes and that dopaminergic function may be key in under...
GRM7 variants confer susceptibility to age-related hearing impairment
2009-01-01
Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The study was performed using 846 cases and 846 controls selected from 3434 individuals collected by eight centers in six European countries. DNA pools for cases and controls were allelotyped on the Affymetrix 500K GeneChip for each center separately. The 252 top-ranked single nucleotide polymorphisms (SNPs) identified in a non-Finnish European sample group (1332 samples) and the 177 top-ranked SNPs from a Finnish sample group (360 samples) were confirmed using individual genotyping. Subsequently, the 23 m...
Effect of Varicocele Grade and Age on Seminal Parameters
2010-01-01
Abstract Aim: To evaluate the effect of presence, grade and anatomical side of varicocele on semen parameters and to identify age-related modifications in semen quality in men with varicocele. Methods: A prospective clinical study was performed in 363 men with varicocele and 155 normozoospermic men without varicocele. We determined the presence, grade and anatomical localization of varicocele: left (grades I-III), right or bilateral. Additionally, evaluation of semen was done and the hypoosmotic swelling test (HOST) percentage determined. Results: The percentage of spermatozoa with normal morphology, motility, vitality, and HOST was reduced in patients with varicocele. Comparison of semen parameters between the different degrees of left varicocele (I, II or III) shows that the percentage o...
Computer simulation study of self irradiation in plutonium
2007-01-01
There is clear experimental evidence that plutonium based materials exhibit density changes with time. By comparison to what is known for nuclear fuel cell aging, it is believed that this phenomenom could be linked to the radioactive Formula Not Shown -decay of plutonium. Schwartz et al. have identified three possible age-related phenomena due to self irradiation in Pu alloys that would cause dimensional changes: the initial transient, helium accumulation and void swelling [A.J. Schwartz, M.A. Wall, T.G. Zocco, W.G. Wolfer, Philos. Mag. 85 (2005) 479]. Even if the later phenomenon has not yet been observed in naturally aged Pu alloys, the aim of this work is to examine its possible occurrence by means of a multi-scale modelling approach. We coupled classical molecular dynamics simulations ...
2009-01-01
Oxidative stress, inflammation and free-radical damage to mitochondria have been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's. Various risk factors have been associated with age-related cognitive decline, including hypertension, obesity, diabetes, metabolic syndrome, history of anxiety/depression, elevated homocysteine levels, inflammation, alcohol intake, smoking and diet. Epidemiological, clinical and preclinical studies have shown that some traditional herbal, mind-body and nutraceutical treatments are effective in preventing age-related cognitive decline. Limited research has been conducted on the benefits of such treatments on neurodegenerative disorders such as Parkinson's disease Publisher: Australian Pharmaceutical Publishing Company Other identifier: swin:14404 Language: English Source: Journal of Complementary Medicine, Vol. 8, no. 5 (Sep-Oct 2009), pp. 12-19 Rights: Copyright 2009.
Childhood metabolic disorders of the central nervous system
1988-01-01
MR (1.5 T) findings were correlated with clinical and laboratory data in seven children with nonketotic hyperglycinemia (NKH) and 12 children with cystinosis. Two distinct patterns of central nervous system (CNS) involvement were seen. In NKH, progressive (age-related), diffuse CNS atrophy was demonstrated in six of seven patients (86%). Decreased or absent myelination was seen in all four patients older than 10 months. Myelination delay shown by MR imaging correlated well with known pathologic findings in this disorder. In cystinosis, the diffuse CNS atrophy detected in 11 of 12 patients (92%) was not age-related. The degree of myelination was normal in all patients. Plaquelike, white-matter lesions were also identified in two patients (17%). MR imaging is a sensitive method for detecting CNS abnormalities that accompany childhood aminoacidopathies
Age-related regional variations of the corpus callosum identified by diffusion tensor tractography
2010-01-01
The corpus callosum is the largest white matter connection in the human brain, and an understanding of its evolution with age in healthy individuals is one crucial aspect for determining its role in cognition and disease. Diffusion tensor imaging (DTI) allows for investigation of age-related callosal changes since tractography can both virtually reconstruct the segments of the corpus callosum in vivo based on unique target cortical regions, and provide quantitative diffusion parameters reflecting tissue microstructure. DTI tractography was used to subdivide the corpus callosum into seven distinct sections based on unique target areas (i.e., orbital frontal, anterior frontal, superior frontal, superior parietal, posterior parietal, temporal, and occipital) in a very large number of healthy ...
Age-related multi-year associations in female humpback whales (Megaptera novaeangliae)
2010-01-01
Analyses of social structures in baleen whales are rare, and so far, they are thought to consist of mostly short and unstable associations. We investigated the association patterns of individual humpback whales from a summer feeding aggregation in the Gulf of St. Lawrence from 1997 to 2005. Photo-identified animals were sexed using genetic methods and were grouped into five categories: juvenile males/females, mature males and lactating/non-lactating females. We calculated half-weight association indices within and between the groups and found that 45% of the observation showed single animals and another 45% small groups (two to three) consisting mainly of mature animals besides lactating females. Using permutation tests, we found evidence for long-term associations between mature males and...
2009-01-01
A fundamental, yet rarely tested premise of developmental cognitive neuroscience is that changes in brain activity and improvements in behavioral control across adolescent development are related to brain maturational factors that shape a more efficient, highly-interconnected brain in adulthood. We present the first multimodal neuroimaging study to empirically demonstrate that maturation of executive cognitive ability is directly associated with the relationship of white matter development and age-related changes in neural network functional integration. In this study, we identified specific white matter regions whose maturation across adolescence appears to reduce reliance on local processing in brain regions recruited for conscious, deliberate cognitive control in favor of a more widely ...
Age effects on carbon fluxes in temperate pine forests
2010-01-01
This study evaluates age-related patterns of ecosystem carbon (C) fluxes in a chronosequence (5-, 18-, 33-, and 68-year old in 2007) of planted pine (Pinus strobus L.) forests in southern Ontario, Canada, from 2003 to 2007. Carbon fluxes determined with the eddy covariance technique were normalized by differences in site index (SI; a measure of site quality based on a species-specific relationship between the height of the dominant trees and base age), to identify the effect of stand age on gross ecosystem productivity (GEP), ecosystem respiration (RE), and net ecosystem productivity (NEP). Observed GEP, RE, and NEP were highest in the 18-year-old stand, which differed from the two older stands by having a higher SI due to sustained availability of soil water in deeper soil layers (at ~1m ...
Pain perception and processing in ageing and Alzheimer's disease
2008-01-01
The prevalence of chronic pain is known to increase with advancing age, with over 50% of community dwelling older adults (aged 65 years and over) and up to 80% of those residing in nursing homes estimated to be suffering some form of persistent or recurring pain complaint. In addition to a greater likelihood of pain, advancing age is associated with increased reports of pain interference. It is possible to ascribe age-related changes in pain report and impact to increased disease prevalence and severity in older people. However, there is also evidence that ageing has effects on pain perception, central pain processing, and plasticity of pain responses that are not explained by co-morbid disease.The increased prevalence of chronic pain in older adults represents a major public health concern. As a result of increased life expectancy and the post-World War II baby boom, there will be a dramatic change in the demographic structure of our population over the coming decades, with older adults representing the fastest-growing segment of our communities. The proportion of the total population over the age of 65 in Australia has risen from 9% in 1976, to 12% in 2001, and is predicted to reach 16% by the year 2016. Pain that is undetected or under-treated can adversely affect quality of life for older adults, leading to diminished mood, impaired cognition, behavioural problems, as well as increased functional dependence. This in turn contributes to greater demands for daily personal care and a resultant increase in health-care costs.Pain management is a particularly salient issue in the case of older adults with dementia, who are at increased risk of undetected pain on account of impaired cognition and communication skills. Indeed, clinical reports show that patients with Alzheimer’s disease (AD) are routinely administered fewer pain-relief medications compared with their cognitively-intact peers. Understandably, reports of reduced analgesia in AD have sparked considerable research interest, and over recent years there has been a marked increase in the number of studies aimed at better characterising the experience of pain in patients with AD. However, despite these efforts, the effects of neurodegeneration on pain processing, and the specific ways in which the disease process impacts on brain responses to noxious stimulation and the ensuing experience of pain have not been previously determined.Improved management of pain is fundamental to the clinical care of older adults, particularly those with dementia. However, the potential to adequately counteract pro-nociceptive processes and facilitate endogenous inhibitory mechanisms in the treatment of ongoing pain in older adults will only become possible once the effects of ageing and age-related neurodegeneration on central pain processing are identified and described. The overarching goal of this thesis was therefore to improve current understanding of the ways in which normal ageing and Alzheimer’s disease impact on the perception and central nervous system processing of pain. The findings of this thesis provide valuable new insights into the impact of ageing and AD on the central mechanisms contributing to pain perception, and may therefore contribute toward better management and treatment of pain in this vulnerable and rapidly growing sector of our community.Thesis outline: Chapter 2 provides a review of the background literature and rationale for the thesis. The chapter begins with a discussion of current understanding of pain as a multidimensional phenomenon shaped by sensory, emotional and cognitive components, and leads into a description of neural mechanisms of nociception, as well as the supraspinal processes involved in the elaboration of nociceptive signals into these aspects of pain. The impact of ageing on the structure and function of central nervous system regions underlying these processes are discussed, along with the findings from previous clinical and empirical data which suggest age-related changes in pain perception. Current understanding of the neuropathological and clinical aspects of AD is reviewed, with particular emphasis on potential ways in which the disease may impact on central nociceptive processing and the behavioural response to pain. This is followed by a review of the previous clinical and empirical literature examining pain perception in AD. Finally, the aims of the current thesis are outlined.Chapter 3 describes the general methods which were employed in the subsequent empirical chapters in order to address the aims of the thesis. The equipment and psychophysical procedures used to assess pain perception in healthy young and older adults and patients with AD are described. The basic principals of magnetic resonance imaging (MRI) are then outlined, and the utility of structural and functional MRI for assessing age-related and disease-related changes to brain regions involved in pain perception and processing are discussed. The empirical studies which were undertaken to identify the impact of ageing and AD on central pain processing are presented in the next three chapters.Chapter 4 begins with psychophysical studies comparing sensory and emotional responses to pain in healthy young and older adults, and follows with MRI investigations of age-related differences in brain volumetry and pain-related brain activity. Studies of pain sensitivity and pain-evoked brain activity in patients with AD compared with age-matched controls are presented in Chapter 5. Following on from these findings of AD-related differences in pain-evoked brain activation, the study described in Chapter 6 used functional connectivity analysis in order to assess the impact of AD on the functional integration of brain regions underlying the sensory, emotional, and cognitive aspects of pain.The key findings presented in the preceding three chapters are summarized in a general discussion in Chapter 7. The implications of the findings, in terms of the clinical management of pain in older adults with and without Alzheimer’s disease are discussed. The opportunity is also taken to discuss some of the limitations of the present research, and finally, recommendations are made for future research directions. Language: eng Rights: Restricted Access: Abstract and Citation Only
Resveratrol and red wine, healthy heart and longevity
2010-01-01
Resveratrol, a polyphenol phytoalexin, present in red wine and grapes possesses diverse biochemical and physiological properties, including estrogenic, antiplatelet, and anti-inflammatory properties as well as a wide range of health benefits ranging from chemoprevention to cardioprotection. Recently, several studies described resveratrol as an anti-aging compound. This review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action, and emerging controversy on its life-prolonging ability. It appears that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect a...
RNA Interference in Ageing Research - A Mini-Review
2010-01-01
Abstract Background: The search for genetic mechanisms affecting life-span and ageing represents an important part of ageing research, especially since the discovery of single-gene mutations with dramatic effects on these traits. Due to its relative ease of use and its power to specifically target arbitrary genes, RNA interference (RNAi) has rapidly been adopted as a technique for silencing gene expression. The feasibility of genome-wide RNAi screens potentially much simplifies the identification of novel ageing-related genes. Objective: In a review of applications of RNAi in ageing research with a focus on the model organisms Caenorhabditis elegans and Drosophila melanogaster and discussing recent technical developments, we aim to highlight the current and future impact of this technology...
2009-01-01
Even successful aging is associated with regional brain shrinkage and deterioration of the cerebral white matter. Aging also brings about an increase in vascular risk, and vascular impairment may be a potential mechanism behind the observed patterns of aging. The goals of this study were to characterize the normal age differences in white matter integrity in several brain regions across the adult life span and to assess the modifying effect of vascular risk on the observed pattern of regional white matter integrity. We estimated fractional anisotropy and diffusivity of white matter in nine cerebral regions of interest in 77 healthy adults (19-84 years old). There was a widespread reduction of white matter anisotropy with age, and prefrontal and occipital regions evidenced the greatest age-...
On the morphology of some irradiated ultra high molecular weight polyethylenes
2009-01-01
The morphology of various grades of ultra high molecular weight polyethylene (UHMWPE), prepared for use in orthopaedic implants, has been examined using differential scanning calorimetry (DSC), wide and small angle X-ray diffraction (WAX and SAX) and Raman spectroscopy. Preparation included gamma irradiation at various dose rates and mechanical annealing, and post-irradiation changes were of particular interest. The experimental results are interpreted in terms of previous proposals that UHMWPE is best considered as a three phase material, fully amorphous, all-trans amorphous and fully crystalline. The all-trans amorphous material is thought to be interfacial. The phase analysis shows that the age related increase in crystallinity occurs through conversion of all-trans material to fully cr...
Molecular mechanisms of proteasome plasticity in aging
2010-01-01
The ubiquitin-proteasome pathway plays a crucial role in regulation of intracellular protein turnover. Proteasome, the central protease of the pathway, encompasses multi-subunit assemblies sharing a common catalytic core supplemented by regulatory modules and localizing to different subcellular compartments. To better comprehend age-related functions of the proteasome we surveyed content, composition and catalytic properties of the enzyme in cytosolic, microsomal and nuclear fractions obtained from mouse livers subjected to organismal aging. We found that during aging subunit composition and subcellular distribution of proteasomes changed without substantial alterations in the total level of core complexes. We observed that the general decline in proteasomes functions was limited to nuclea...
2009-01-01
Aging is associated with an increased production of free radicals and alterations in the mechanisms of adaptation to stress. A number of studies have shown a causal connection between age-related oxidant/antioxidant imbalance and the diminution of an organisms melatonin levels in old age. Restoration of this rhythm may contribute to the re-stabilization of cellular homeostasis. The present work was aimed at examining the effect of the administration of melatonin or its precursor, the amino acid tryptophan, on heterophil lipid peroxidation (LPO) levels and superoxide dismutase (SOD) activity in heterophils from young (45year) and old (1214year) ringdoves (Streptopelia risoria) under both basal and antigen-induced (stressful) conditions. Young animals were treated for 3 consecut...
Mechanisms and measurements of nanomaterial-induced oxidative damage to DNA
2010-01-01
Many of the current investigations on the environmental and human health risks of engineered nanomaterials focus on their short-term acute toxicity. However, the long-term chronic effects of nanomaterials on living systems, and in particular, on the genetic components of living systems, also warrant attention. An increasing number of nanomaterial safety studies include an assessment of genotoxicity as part of the overall risk evaluation. The potential of nanomaterials to directly or indirectly promote the formation of reactive oxygen species is one of the primary steps in their genotoxic repertoire. The subsequent modification of genomic DNA by reactive oxygen species could lead to the development of mutagenesis, carcinogenesis, or other age-related diseases if the DNA damage is not repair...
1993-01-01
Economic factors have contributed to the decision to close Yankee Rowe, San Onofre Unit 1, and Trojan nuclear plants. As nuclear plants age, uncertainties related to major component and system replacement can affect their capital cost contribution to the price of electricity. These costs, their timing, and associated uncertainties can be prohibitive if the remaining plant life is too short. However, these costs may be acceptable if plant service life is extended. Life-cycle management (LCM) is a method of evaluating those options which ultimately affect the useful life of a power plant. This paper presents the methods and an example of an LCM evaluation of a Salt Water Service Water System. Cost-benefit analyses were developed by quantifying age-related degradation mechanisms for various lining and replacement materials, determining their probabilistic life ...
Inflammatory, Apoptotic, and Survival Gene Signaling in Alzheimers Disease
2010-01-01
Aging is associated with an enhanced susceptibility to brain dysfunction, loss of memory, and cognitive decline and significantly influences the quality of life for the affected individual. Recent moleculargenetic approaches have provided powerful insights into common age-related diseases that are both progressive and multifactorial, such as Alzheimers disease (AD), and in vitro in AD models. These investigations have uncovered consistent deficits in brain gene signaling mechanisms and neurotrophic substances known to contribute to normal brain function. Inflammatory signaling pathways involving up-regulation of cytosolic phospholipase A2 and the arachidonic acid cycle, the depletion of the brain-essential fatty acid docosahexaenoic acid (DHA) and DHA-derived neuroprotectin D1, and c...
Flavonoids and age-related disease: Risk, benefits and critical windows
2010-01-01
Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive ...
Differential inflammatory responses in aging and disease: TNF-a and IL-6 as possible biomarkers
2010-01-01
Oxidative stress has been reported to increase during aging and conditions of hypoxia. Although low oxygen saturation has a key role in the development of several age-related diseases, the underlying mechanisms are still unknown. We analyzed the relationship between aging and hypoxia by examining oxidative stress and inflammation-related cytokines. We collected blood samples from three volunteer experimental groups, consisting of one group of normoxic middle-aged people and two groups of individuals older than 75years, which comprised a subgroup of normoxic subjects and another with oxyhemoglobin saturation lower than 95% (hypoxic). Our results showed a fall in antioxidant defenses in older people with hypoxia. TNF-a, the first element in the cytokine cascade, was significantly increased i...
Differential age-related changes in mitochondrial DNA repair activities in mouse brain regions
2010-01-01
Aging in the brain is characterized by increased susceptibility to neuronal loss and functional decline, and mitochondrial DNA (mtDNA) mutations are thought to play an important role in these processes. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (BER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defence against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. In the current study we investigated the efficiency of the BER pathway through...
2010-01-01
Although empathy is rooted early in life, the ability to understand and share the emotions of others continues to develop after childhood. Here, we aimed at exploring developmental changes in the neural mechanisms underlying empathy from childhood to early adulthood. Using functional magnetic resonance imaging, 47 healthy male subjects aged 827years were investigated during an explicit empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). A perceptual decision on the width of faces was used as a control condition. Age-related activity increases were observed in the fusiform gyrus and inferior frontal gyrus, depending on whether subjects at...
2010-01-01
How will the worldwide decline in real interest rates associated with global ageing affect small open economies (SOEs) with ageing populations? Lower interest rates will result in higher capital–labor ratios and increased wages. Higher wages will be passed on to pension benefits, exacerbating ageing-related fiscal pressures, increasing taxation and reducing consumption and welfare. The pass-through effect will be stronger if pensions are indexed to nominal wages rather than prices. The article illustrates the interest rates transmission mechanism and its interaction with pension indexation. In addition, the article evaluates the capacity of pension reforms to mitigate the effects of long-run movements in world interest rates. It concludes that pension reforms, particularly those that...
2008-01-01
Age-related decline in maximal concentric muscle power is associated with frailty and functional impairments in the elderly. Compared to concentric contraction, mechanical muscle output is generally enhanced when muscles are rapidly pre-stretched (eccentric contraction), albeit less pronounced with increasing age. Exercise has been recommended to prevent loss of muscle power and function and recent guidelines indicate training program for increasing muscle power highly relevant for elderly subjects. This study examined the differences in muscle power, force and movement pattern during concentric-alone and coupled eccentricconcentric contraction and selected functional motor performances before and after 36-week multicomponent training including aerobic, strength, balance, flexibility an...
2010-01-01
Objective Autophagy is a process for turnover of intracellular organelles and molecules that protects cells during stress responses. We undertook this study to evaluate the potential roles of Unc-51-like kinase 1 (ULK1), an inducer of autophagy, Beclin1, a regulator of autophagy, and microtubule-associated protein 1 light chain 3 (LC3), which executes autophagy, in the development of osteoarthritis (OA) and in cartilage cell death. Methods Expression of ULK1, Beclin1, and LC3 was analyzed in normal and OA human articular cartilage and in knee joints of mice with aging-related and surgically induced OA, using immunohistochemistry and Western blotting. Poly(ADP-ribose) polymerase (PARP) p85 expression was used to determine the correlation between cell death and autophagy. Results ULK1, Becli...
Aging characteristics of containment building and sensitivity on ultimate pressure capacity
1998-03-01
For the reliable safety assessment of the containment building, structural and material conditions can be investigated in detail and pertinent assessment technologies have to be established. Also, an understanding on the aging-related degradations for the construction materials is required to predict long-term structural safety of the containment building. For the development of reliable aging prediction models, an extensive data base system related to aging properties of the containment building has to be prepared. The objectives of this research are to develop aging models representing long-term degradation of materials and a structural performance assessment program for containment building considering aging-related degradation. According to the results of sensitivity analysis, as the mechanical properties of the constituent materials degrade, the ultimate pressure capacity of containment building may decrease and severe damage may occur around the mid-level of the containment wall. (author). 28 refs., 11 tabs., 36 figs.
Age-related changes in grey and white matter structure throughout adulthood
2010-01-01
Normal ageing is associated with gradual brain atrophy. Determining spatial and temporal patterns of change can help shed light on underlying mechanisms. Neuroimaging provides various measures of brain structure that can be used to assess such age-related change but studies to date have typically considered single imaging measures. Although there is consensus on the notion that brain structure deteriorates with age, evidence on the precise time course and spatial distribution of changes is mixed. We assessed grey matter (GM) and white matter (WM) structure in a group of 66 adults aged between 23 and 81. Multimodal imaging measures included voxel-based morphometry (VBM)-style analysis of GM and WM volume and diffusion tensor imaging (DTI) metrics of WM microstructure. We found widespread re...
2009-04-02
The Korea Atomic Energy Research Institute (KAERI) and Brookhaven National Laboratory (BNL) are collaborating to develop seismic capability evaluation technology for degraded structures and passive components (SPCs) under a multi-year research agreement. To better understand the status and characteristics of degradation of SPCs in nuclear power plants (NPPs), the first step in this multi-year research effort was to identify and evaluate degradation occurrences of SPCs in U.S. NPPs. This was performed by reviewing recent publicly available information sources to identify and evaluate the characteristics of degradation occurrences and then comparing the information to the observations in the past. Ten categories of SPCs that are applicable to Korean NPPs were identified, comprising of anchorage, concrete, containment, exchanger, filter, piping system, reactor pressure vessel, structural steel, tank, and vessel. Software tools were developed to expedite the review process. Results from this review effort were compared to previous data in the literature to characterize the overall degradation trends.
Suppressing a gene in mice prevents heart from aging, preserves its function
2009-10-12
In a mouse study, suppressing the activity of a key gene prevented age-related cardiac changes and preserved much of the heart's function. The study provides more evidence that physicians may one day prevent age-related ...
Brain training reverses age-related cognitive decline
2010-07-19
Specialized brain training targeted at the regions of a rat's brain that process sound reversed many aspects of normal, age-related cognitive decline and improved the health of the brain cells, according to a new study ...
A spectroscopy study of nearby late-type stars, possible members of stellar kinematic groups
2010-07-08
Nearby late-type stars are excellent targets for seeking young objects in stellar associations and moving groups. The origin of these structures is still misunderstood, and lists of moving group members often change with time and also from author to author. Most members of these groups have been identified by means of kinematic criteria, leading to an important contamination of previous lists by old field stars. We attempt to identify unambiguous moving group members among a sample of nearby-late type stars by studying their kinematics, lithium abundance, chromospheric activity, and other age-related properties. High-resolution echelle spectra ($R \\sim 57000$) of a sample of nearby late-type stars are used to derive accurate radial velocities that are combined with the precise Hipparcos parallaxes and proper motions to compute galactic-spatial velocity components. Stars are classified as possible members of the classical moving groups according to their kinematics. The spectra are also used to study several age-related properties for young late-type stars, i.e., the equivalent width of the lithium Li~{\\sc i} \\space 6707.8 \\space \\AA \\space line or the $R'_{\\rm HK}$ index. Additional information like X-ray fluxes from the ROSAT All-Sky Survey or the presence of debris discs is also taken into account. The different age estimators are compared and the moving group membership of the kinematically selected candidates are discussed. From a total list of 405 nearby stars, 102 have been classified as moving group candidates according to their kinematics. i.e., only $\\sim$ 25.2 \\% of the sample. The number reduces when age estimates are considered, and only 26 moving group candidates (25.5\\% of the 102 candidates) have ages in agreement with the star having the same age as an MG member
Effects of age on the distortion product otoacoustic emission growth functions.
Age-related hearing loss (presbycusis) is thought to result from age-related degeneration (aging) of the cochlea plus the cumulative effects of extrinsic damage (noise and other ototoxic agents) and intrinsic disorders (e.g. systemic diseases). Previous studies have implicated dysfunction of the hair cells (sensory presbycusis) as the principal mechanism of age-related hearing loss. However, recent evidence from quiet-reared gerbils suggests that cochlear aging results primarily from atrophy of the stria vascularis, which is associated with diminished endocochlear potential (EP), spiral ganglion atrophy, and a relatively flat audiometric loss, termed metabolic presbycusis. Because it is not currently possible to measure EP directly in the clinical setting, we wondered if cochlear metabolic dysfunction might be evidenced indirectly from existing clinical tests, specifically, the input-output (IO) growth function of the distortion product (DP) otoacoustic emissions in relation to behavioral hearing threshold levels (HTL). We anticipated finding discordance between the IO functions and HTL with either a greater decline with age in HTL than in IO functions if an age-related metabolic dysfunction of the cochlea was operant, or a greater loss of IO function than HTL if outer hair cell dysfunction was the dominant pathology. To address this supposition we analyzed existing auditory data from a large cohort of adults to determine the change with age in three aspects of the DP IO function: area under the curve, threshold, and slope. The analyses demonstrated a greater effect of age on HTL than on the DP IO measures. This effect supports the hypothesis that strial dysfunction is a substantive factor in cochlear aging. The etiology and mechanisms for this dysfunction are conjectural at present.
Use of sham radiotherapy in randomized clinical trials
2008-01-01
The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970–2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used. Publisher: ePublications@bond Source: Health Sciences & Medicine papers
NYU researchers identify a key mechanism in the brain's computation of sound location
2010-06-29
NYU researchers have identified a mechanism the brain uses to help process sound localization. Their findings focus on how the brain computes the different arrival times of sound into each ear to estimate the location ...
Key mechanism in the brain's computation of sound location identified
2010-06-29
Animals can locate the source of a sound by detecting microsecond (one millionth of a second) differences in arrival time at their two ears. New York University researchers have identified a mechanism the brain uses to ...
WRN Exonuclease Structure, Molecular Mechanism, and DNA EndProcessing Role
WRN is unique among the five human RecQ DNA helicases by having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end-joining. Metal ion complex structures, active site mutations and activity assays reveal a two-metal-ion mediated nuclease mechanism. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end-joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ family replicative proofreading exonucleases, with WRN-specific adaptations consistent with dsDNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support analogous proof-reading activities that are stimulated by Ku70/80 with implications for WRN functions in age related pathologies and maintenance of genomic integrity.
WRN Exonuclease Structure, Molecular Mechanism, and DNA EndProcessing Role
WRN is unique among the five human RecQ DNA helicases by having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end-joining. Metal ion complex structures, active site mutations and activity assays reveal a two-metal-ion mediated nuclease mechanism. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end-joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ family replicative proofreading exonucleases, with WRN-specific adaptations consistent with dsDNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support analogous proof-reading activities that are stimulated by Ku70/80 with implications for WRN functions in age related pathologies and maintenance of genomic integrity.
WRN Exonuclease Structure, Molecular Mechanism, and DNA EndProcessing Role
2006-02-15
WRN is unique among the five human RecQ DNA helicases by having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end-joining. Metal ion complex structures, active site mutations and activity assays reveal a two-metal-ion mediated nuclease mechanism. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end-joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ family replicative proofreading exonucleases, with WRN-specific adaptations consistent with dsDNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support analogous proof-reading activities that are stimulated by Ku70/80 with implications for WRN functions in age related pathologies and maintenance of genomic integrity.
The Influence of Perceptual Training on Working Memory in Older Adults
Full Text Available.Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.
Full Text Available. Caloric restriction (CR), in the absence of malnutrition, delays aging and prevents aging-related diseases through multiple mechanisms. A reduction in chronic inflammation is widely observed in experimental models of caloric restriction. The low inflammation status may contribute to the reduced incidence of osteoporosis, Alzheimer's disease, cardiovascular diseases and cancer in the aging subjects. The association of caloric restriction with low inflammation suggests a role of energy accumulation in the origin of the chronic inflammation. This point is enforced by recent advances in obesity research. Abundant literature on obesity suggests that chronic inflammation is a consequence of energy accumulation in the body. The emerging evidence strongly supports that the inflammatory response induces energy expenditure in a feedback manner to fight against energy surplus in obesity. If this feedback system is deficient (Inflammation Resistance), energy expenditure will be reduced and energy accumulation will lead to obesity. In this perspective, we propose that an increase in inflammation in obesity promotes energy expenditure with a goal to get rid of energy surplus. A decrease in inflammation under caloric restriction contributes to energy saving. Inflammation is a mechanism for energy balance in the body. Inflammation resistance will lead to obesity. We will review the recent literature in support of the viewpoints.
2009-01-01
The aim of this cross-sectional study was to delineate age-associated kinematic and kinetic gait patterns of normal walking, and to test the hypothesis that older adults exhibit gait patterns that reduce generative mechanical work expenditures (MWEs). We studied 52 adult Baltimore Longitudinal Study of Aging participants (means age 72+-9, from 60 to 92 years) who could walk 4m unaided. Three-dimensional kinematic and kinetic parameters assessed during rotation-defined gait periods were used to estimate MWEs for the rotation of lower extremities about the medial-lateral (ML) and anterior-posterior (AP) axes of proximal joints, which represent MWEs in the AP and ML sides, respectively. Relationships between gait parameters and age were examined using regression analysis with adjustments for ...
Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians
Full Text Available.BackgroundAge-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.Methodology/Principal FindingsBy using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.Conclusions/SignificanceWe provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
PURPOSE: To describe a neovascular pattern associated with treatment-refractory neovascular age-related macular degeneration (AMD). DESIGN: A retrospective observational case series. METHODS: SETTING: Clinical practice. PATIENT POPULATION: Twelve eyes of 12 patients with neovascular AMD in which a poor anatomic response to anti-vascular endothelial growth factor (VEGF) therapy was related to polypoidal choroidal vasculopathy (PCV). OBSERVATION PROCEDURE: Slit-lamp biomicroscopy, optical coherence tomography, fluorescein and indocyanine green angiography. MAIN OUTCOME MEASURES: Snellen visual acuity (VA), anatomic response to therapy including presence or absence of retinal edema, hemorrhage, and lipid exudates. RESULTS: New or persistent PCV was identified in a cohort of patients demonstrating increasing macular exudation despite regular intravitreal ranibizumab (Lucentis; Genentech Inc, South San Francisco, California, USA) or bevacizumab (Avastin; Genentech Inc) injections for a minimum of 6 months. Treatment with verteporfin photodynamic therapy (PDT), PDT/anti-VEGF combination therapy, or continued anti-VEGF monotherapy resulted in complete resolution of exudation in 9 of 12 patients and partial resolution of exudation in the remaining 3 patients. CONCLUSION: Treatment-refractory neovascular AMD may harbor vascular abnormalities such as PCV. Modifications in therapeutic protocols may be indicated in order to improve visual and anatomic outcomes in this population.
Learning at Old Age: A Study on Winter Bees
Full Text Available.Ageing is often accompanied by a decline in learning and memory abilities across the animal kingdom. Understanding age-related changes in cognitive abilities is therefore a major goal of current research. The honey bee is emerging as a novel model organism for age-related changes in brain function, because learning and memory can easily be studied in bees under controlled laboratory conditions. In addition, genetically similar workers naturally display life expectancies from 6 weeks (summer bees) to 6 months (winter bees). We studied whether in honey bees, extreme longevity leads to a decline in cognitive functions. Six-month-old winter bees were conditioned either to odours or to tactile stimuli. Afterwards, long-term memory and discrimination abilities were analysed. Winter bees were kept under different conditions (flight/no flight opportunity) to test for effects of foraging activity on learning performance. Despite their extreme age, winter bees did not display an age-related decline in learning or discrimination abilities, but had a slightly impaired olfactory long-term memory. The opportunity to forage indoors led to a slight decrease in learning performance. This suggests that in honey bees, unlike in most other animals, age per se does not impair associative learning. Future research will show which mechanisms protect winter bees from age-related deficits in learning.
Inner Retina Remodeling in a Mouse Model of Stargardt-like Macular Dystrophy (STGD3)
2010-04-01
Full Text Available.Purpose.To investigate the impact of progressive age-related photoreceptor degeneration on retinal integrity in Stargardt-like macular dystrophy (STGD3).Methods.The structural design of the inner retina of the ELOVL4 transgenic mouse model of STGD3 was compared with that of age-matched littermate wild-type (WT) mice from 1 to 24 months of age by using immunohistofluorescence and confocal microscopy and by relying on antibodies against cell-type–specific markers, synapse-associated proteins, and neurotransmitters.Results.Müller cell reactivity occurred at the earliest age studied, before photoreceptor loss. This finding is perhaps not surprising, considering the cell's ubiquitous roles in retina homeostasis. Second-order neurons displayed salient morphologic changes as a function of photoreceptoral input loss. Age-related sprouting of dendritic fibers from rod bipolar and horizontal cells into the ONL did not occur. In contrast, with the loss of photoreceptor sensory input, these second-order neurons progressively bore fewer synapses. After rod loss, the few remaining cones showed abnormal opsin expression, revealing tortuous branched axons. After complete ONL loss (beyond 18 months of age), localized areas of extreme retinal disruptions were observed in the central retina. RPE cell invasion, dense networks of strongly reactive Müller cell processes, and invagination of axons and blood vessels were distinctive features of these regions. In addition, otherwise unaffected cholinergic amacrine cells displayed severe perturbation of their cell bodies and synaptic plexi in these areas.Conclusions.Remodeling in ELOVL4 transgenic mice follows a pattern similar to that reported after other types of hereditary retinopathies in animals and humans, pointing to a potentially common pathophysiologic mechanism.
2007-08-15
Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional {alpha}-[{sup 11}C]methyl-L-tryptophan ({alpha}-[{sup 11}C]MTrp) trapping rate constant (K*; {mu}l.g{sup -1}.min{sup -1}), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with {alpha}-[{sup 11}C]MTrp [18 males aged 46.6 {+-} 22.2 years (range 20-80 years) and 18 females aged 33.0 {+-} 15.5 years (range 20-80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and {alpha}-[{sup 11}C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process. (orig.)
Aging mechanisms - An overview
1995-12-31
Human Aging: Aging is an extensively studied subject related to humans yet no theory is well accepted as the theory of aging. Since human aging has social, political and economical implications, research directions are numerous. As a result there are chemistry, biology, physiology, psychology and other frameworks of aging. Despite human aging has been studied for a long time, the National Institute of Aging was established only in 1976. Aging related costs were estimated to be over $100 billion a year in the 1980`s. This is expected to increase as the percentage of people entering age 65 and above in the next decade will also increase representing 15% of the American population. Aging Structures: The engineering utilities designed after World War II are experiencing aging. The mechanisms of aging in engineering artifacts are not well understood as the design considerations then were based on macroscopic (Theological behavior) properties only. Fatigue considerations used in design then are now becoming inadequate. Concepts such as corrosion, erosion, creep, wear, fretting, thermal shock, thermal-mechanical fatigue, multiaxial effects, hydrogen effects, environmental degradations and other potential mechanisms and their interactions with one or more of these processes are appearing as significant candidate mechanisms. As a result, aging mechanisms cannot be separated in terms of crack formation and growth to fracture. Additionally, degradations in the microstructure or depletion, embrittlement with time, hydrogen entrapment and other time dependent transformations which also degrade material properties must be considered. An attempt has been made in this paper to overview the mechanisms of aging structures.
42 CFR 433.138 - Identifying liable third parties.
...mechanized claims processing and information retrieval system. Basic requirement...mechanized claims processing and information retrieval system approved by CMS under...mechanized claims processing and information retrieval system. (2) The...
Fractal analysis of cancellous bone in disease
2002-01-01
The principal aim of this thesis was to develop and implement a standardised protocol for the fractal analysis of cancellous bone architecture. Cancellous bone structure from different skeletal sites in groups of osteoporotic, osteoarthritic and normal individuals was analysed. The results of fractal analysis were explained in the context of conventional bone histomorphometry and a priori knowledge to advance the understanding of cancellous bone architecture. There has been much effort devoted to the pursuit of descriptors of cancellous bone complexity. The aim of these endeavours has been to develop morphological descriptors of bone quality that explain the functional properties of the cancellous bone structure for age-related changes, the effect of disease processes or the effect of therapeutic agents on the diseased skeleton. The fractal analysis of the complexity of cancellous bone architecture promises to be an exciting addition to existing analytical techniques. The establishment of a standardised methodology for the fractal analysis of cancellous bone encompassed many components. Knowledge of the stereological and histomorphometric principles that are employed in currently available techniques enabled a comprehensive examination of the factors that effect the measurement of the fractal dimensions. The methodology presented in this thesis has been optimised specifically for measuring sectional fractal dimensions in histological sections of cancellous bone. The sectional fractal dimensions show that, over three ranges of scale, cancellous bone is effectively fractal at multiple sites in the normal skeleton. The three sectional fractal dimensions describe different morphological compartments of the cancellous bone structure. Fractal 1 describes the surface texture of the trabeculae, fractal 2 describes the shape or form of individual trabeculae and fractal 3 describes the spatial arrangement or overall architecture of the cancellous bone. This thesis reports that in the normal skeleton there are differences between skeletal sites for the fractal dimensions, which are dependent on the functional properties of the skeletal sites. Fractal 2 and fractal 3 for subchondral cancellous bone is greater than vertebral body and iliac crest cancellous bone, which indicates greater morphological complexity. Also, fractal 2 and fractal 3 in subchondral cancellous bone show an age-related decrease, which suggests that the cancellous bone structure becomes less complex with age. This interostotic variability in response to ageing is indicative of the heterogeneity in functional properties of cancellous bone in the skeleton. In this thesis, fractal analysis has been shown to detect morphological differences in the cancellous bone between normals, osteoporotics and osteoarthritics in the compressive and tensile trabeculae of the femoral head and the iliac crest. These data have provided new insights into the mechanisms of change to cancellous bone structure in ageing and in disease. Age-related changes in the structural parameters of cancellous bone are seen at all the skeletal sites in the normals but are only present in the compressive trabeculae of the femoral head in the osteoporotics and not at all in the osteoarthritics. These observations indicate that these disease processes are associated with an uncoupling of the control mechanisms that affect cancellous bone structural complexity. In the normals, the fractal dimensions only show age-related change in the tensile trabeculae of the femoral head, suggesting that fractal analysis is not suitable for detecting the age-related changes that are quantified by the structural parameters of cancellous bone in these study groups but the fractal dimensions detect underlying cancellous bone complexity independent of age. For the osteoporotics, fractal 1 is the same at all skeletal sites. This suggests that the relative levels of remodeling activity are the same for both normals and osteoporotics. Fractal 2 for both the compressive and tensile trabeculae in the femur is significantly lower for the osteoporotics than the normals but in the iliac crest, fractal 2 is the same. This implies that in the femoral head the osteoporotics have trabeculae that are significantly less complex in shape than the normals. This phenomenon is not seen in the iliac crest, which is usually the site of diagnostic biopsy. Therefore, biopsies for diagnosis of osteoporosis may not show changes in cancellous bone structural complexity that are evident in disease affected sites. The structural parameters of cancellous bone show that osteoporotics lose whole trabeculae due to perforation of trabeculae, through decreased Tb.N and increased Tb.Sp. This leads to less interconnection between trabeculae, loss of branching and more rounded trabeculae, hence the trabeculae are less complex in shape. For fractal 3, in compressive and tensile regions of the femur the osteoporotics are significantly lower than the normals and in the iliac crest the osteoporotics are the same as the normals. This indicates that in the femoral head the spatial arrangement of the trabeculae within the cancellous structure of the osteoporotics is less complex. The structural parameters of cancellous bone show that there is loss of whole trabeculae, which is associated with increased spatial separation between the trabeculae as bone is lost. For the osteoarthritics, fractal 1 is the same as the normals at all skeletal sites. Fractal 2 for the compressive trabeculae in the femoral head is significantly higher for the osteoarthritics than the normals but in the tensile trabeculae of the femoral head and the iliac crest fractal 2 for the osteoarthritics is the same as the normals. This implies that in the compressive trabeculae of the femoral head the osteoarthritics have trabeculae that are significantly more complex in shape than the normals. The structural parameters of cancellous bone show that the compressive trabeculae of the femoral head are thicker, more numerous and less widely separated with greater BV/TV than the normals. This leads to greater interconnectivity between trabeculae and more complex branching, hence the trabeculae are more complex in shape. For fractal 3, in the compressive and tensile regions of the femoral head the osteoarthritics and the normals are the same but in the iliac crest the osteoarthritics are lower than the normals. This indicates that the spatial arrangement of the trabeculae within the cancellous structure of the osteoarthritics does not change in response to the disease process in subchondral cancellous bone adjacent to the articular lesion but in the iliac crest the spatial arrangement of the trabeculae in osteoarthritics is less complex in shape. The structural parameters of cancellous bone show that BV/TV is increased in the compressive and tensile trabeculae of the femoral head but not in the iliac crest of the osteoarthritics. This indicates that the spatial complexity of the trabecular arrangement within the cancellous structure of osteoarthritics changes independently of changes in cancellous bone structure detected by the structural parameters of cancellous bone. The sectional fractal dimensions have detected differences in morphological complexity between the normals and disease groups and between the skeletal sites. These novel data have been obtained using an innovative technique that is not dependent on assumptions based on conceptual models of cancellous bone structure. A priori knowledge of bone biology is utilised to enable the fractal analysis to measure specific morphological entities within the cancellous bone structure. The fractal dimensions have identified changes in the morphological complexity of specific components of the cancellous structure, which are not identified by existing model-based morphometric techniques. This has enabled new understanding of how change to cancellous bone structure occurs as a result of a disease process. Fractal analysis is a novel tool that will prove useful for the study of changes in cancellous bone structure due to disease and to study the use of therapies to alter or maintain the quality of cancellous bone architecture.Thesis (Ph.D.)--Medical School, 2002. Language: en_US
The meaning of nuclear war to adult men: A developmental approach
1991-01-01
The study investigated the contextual and thematic meaning of nuclear war. Age-related differences were also investigated by sampling 36 male subjects in three age groups (20-27, 40-50, and above 60). Contextual meaning was measured by asking subjects to rate the meaning of nuclear war and three other threats (personal death, earthquake, and economic depression) on two questionnaires designed to explore personal meaning. Thematic meaning was measured by asking subjects to answer two open-ended questions. In terms of contextual meaning, the study found that, when compared to all other threats, nuclear war has a more extreme emotional meaning. In addition, meaning of nuclear war was found to shift across the adult lift span. In terms of thematic meaning, the study identified five themes describing causation and five themes describing effects. Age differences were found in thematic meaning. Oldest subjects emphasized rational causation, while middle-aged and younger subjects emphasized hopelessness and the impact on either inter-generational or intra-generational relationships. Age differences in meaning are discussed in terms of Eriksonian theory of adult development.
The black hole mass-galaxy age relation
2000-01-01
We present evidence that there is a significant correlation between the fraction of the mass of a galaxy that lies in its central black hole and the age of the galactic stellar population. Since the absorption-line indices that are used to estimate the age are luminosity-weighted, they essentially measure the time since the last significant episode of star formation in the galaxy. The existence of this correlation is consistent with several theories of galaxy formation, including the currently favoured hierarchical picture of galaxy evolution, which predicts just such a relation between the black hole mass and the time since the last burst of merger-induced star formation. It is not consistent with models in which the massive black hole is primordial, and hence uncoupled from the stellar properties of the galaxy. Publisher: Blackwell Science Contributor: Swinburne University of Technology. School of Biophysical Sciences and Electrical Engineering Other identifier: swin:852 Language: English Source: Monthly notices of the Royal Astronomical Society, Vol. 313, no. 2 (Apr. 2000), pp. L29-L32 Rights: Copyright 2000 The Royal Astronomical Society. Author's final draft reproduced here in accordance with the copyright policy of the publisher.
NF1 exon 22 analysis of individuals with the clinical diagnosis of neurofibromatosis type 1
2010-01-01
Cafe-au-lait macules are frequently seen in Ras-MAPK pathway disorders and are a cardinal feature of neurofibromatosis type 1 (NF1). Most NF1 individuals develop age-related tumorigenic manifestations (e.g., neurofibromas), although individuals with a specific 3-bp deletion in exon 22 of NF1 (c.2970_2972delAAT) have an attenuated phenotype with primarily pigmentary manifestations. Previous reports identify this deletion c.2970_2972delAAT in exon 17 of NF1 using NF Consortium nomenclature. For this report, we elected to use standard NCBI nomenclature, which places this identical deletion within exon 22. SPRED1 mutations cause Legius syndrome, which clinically overlaps with this attenuated NF1 phenotype. In an unselected cohort of 50 individuals who fulfilled NIH clinical diagnostic criteria...
Managing aging in nuclear power plants: Insights from NRC`s Maintenance Team Inspection reports
A plant`s maintenance program is the principal vehicle through which age-related degradation is managed. From 1988 to 1991, the NRC evaluated the maintenance program of every nuclear power plant in the United States. Forty-four out of a total of sixty-seven of the reports issued on these in-depth team inspections have been reviewed for insights into the strengths and weaknesses of the programs as related to the need to understand and manage the effects of aging on nuclear plant structures, systems, and components (SSCs). Relevant information has been extracted from these inspection reports sorted into several categories; including Specific Aging Insights, Preventive Maintenance, Predictive Maintenance and Condition Monitoring, Post Maintenance Testing, Failure Trending, Root Cause Analysis and Usage of Probabilistic Risk Assessment in the Maintenance Process. Specific examples of inspection and monitoring techniques successfully used by utilities to detect degradation due to aging have been identified.
Managing aging in nuclear power plants: Insights from NRC`s Maintenance Team Inspection reports
1992-12-31
A plant`s maintenance program is the principal vehicle through which age-related degradation is managed. From 1988 to 1991, the NRC evaluated the maintenance program of every nuclear power plant in the United States. Forty-four out of a total of sixty-seven of the reports issued on these in-depth team inspections have been reviewed for insights into the strengths and weaknesses of the programs as related to the need to understand and manage the effects of aging on nuclear plant structures, systems, and components (SSCs). Relevant information has been extracted from these inspection reports sorted into several categories; including Specific Aging Insights, Preventive Maintenance, Predictive Maintenance and Condition Monitoring, Post Maintenance Testing, Failure Trending, Root Cause Analysis and Usage of Probabilistic Risk Assessment in the Maintenance Process. Specific examples of inspection and monitoring techniques successfully used by utilities to detect degradation due to aging have been identified.
Managing aging in nuclear power plants: Insights from NRC's Maintenance Team Inspection reports
A plant's maintenance program is the principal vehicle through which age-related degradation is managed. From 1988 to 1991, the NRC evaluated the maintenance program of every nuclear power plant in the United States. Forty-four out of a total of sixty-seven of the reports issued on these in-depth team inspections have been reviewed for insights into the strengths and weaknesses of the programs as related to the need to understand and manage the effects of aging on nuclear plant structures, systems, and components (SSCs). Relevant information has been extracted from these inspection reports sorted into several categories; including Specific Aging Insights, Preventive Maintenance, Predictive Maintenance and Condition Monitoring, Post Maintenance Testing, Failure Trending, Root Cause Analysis and Usage of Probabilistic Risk Assessment in the Maintenance Process. Specific examples of inspection and monitoring techniques successfully used by utilities to detect degradation due to aging have been identified.
Managing aging in nuclear power plants: Insights from NRC's Maintenance Team Inspection reports
1992-01-01
A plant's maintenance program is the principal vehicle through which age-related degradation is managed. From 1988 to 1991, the NRC evaluated the maintenance program of every nuclear power plant in the United States. Forty-four out of a total of sixty-seven of the reports issued on these in-depth team inspections have been reviewed for insights into the strengths and weaknesses of the programs as related to the need to understand and manage the effects of aging on nuclear plant structures, systems, and components (SSCs). Relevant information has been extracted from these inspection reports sorted into several categories; including Specific Aging Insights, Preventive Maintenance, Predictive Maintenance and Condition Monitoring, Post Maintenance Testing, Failure Trending, Root Cause Analysis and Usage of Probabilistic Risk Assessment in the Maintenance Process. Specific examples of inspection and monitoring techniques successfully used by utilities to detect degradation due to aging have been identified.
Extracellular signal-regulated kinase-2 phosphorylates ROR4 in vitro
2007-01-01
The retinoic acid related orphan receptor RORα activates transcription of genes that play an important role in cerebellar development, the protection against age-related degenerative processes, the regulation of inflammatory responses, and is one of the pivotal participants that control the circadian rhythmicity in the core-clock of mammals. We identified the extracellular signal-regulated kinase 2 (ERK-2) as RORα4 phosphorylating kinase in vitro. The primary sequence of RORα4 contains an ERK-2 recognition motif (P-L-T128-P) within the hinge domain, and mutation of Thr-128 to Ala prevents RORα4 phosphorylation by ERK. The RORα4-T128A mutant exhibits an increased DNA-binding affinity, an increased transcriptional activity and, in the interplay with the opponent RevErbα, acts as a stronger competitor at ROR response elements than RORα4-WT. Publisher: Academic Press Coverage: 2007-07-06T00:00:00Z
Compounds that Confer Thermal Stress Resistance and Extended Lifespan
2008-10-01
Full Text Available.The observation that long-lived and relatively healthy animals can be obtained by simple genetic manipulation prompts the search for chemical compounds that have similar effects. Since aging is the most important risk factor for many socially and economically important diseases, the discovery of a wide range of chemical modulators of aging in model organisms could prompt new strategies for attacking age-related disease such as diabetes, cancer and neurodegenerative disorders (Collins et al., 2006; Floyd, 2006; Gill, 2006; Hefti and Bales, 2006). Resistance to multiple types of stress is a common trait in long-lived genetic variants of a number of species; therefore we have tested compounds that act as stress response mimetics. We have focused on compounds with antioxidant properties and identified those that confer thermal stress resistance in the nematode Caenorhabditis elegans. Some of these compounds (lipoic acid, propyl gallate, trolox and taxifolin) also extend the normal lifespan of this simple invertebrate, consistent with the general model that enhanced stress resistance slows aging.
2010-01-01
song m., lee m. &shim b. (2009) Barriers to and facilitators of self-management adherence in Korean older adults with type 2 diabetes. International Journal of Older People Nursing 5, 211-218doi: 10.1111/j.1748-3743.2009.00189.x Aim. The aim of this study was to identify the barriers to and facilitators of self-management adherence in Korean older adults with type 2 diabetes. Design and methods. Qualitative data collected from 24 participants in three focus groups who had previously taken part in a diabetes self-management education programme in a community setting were analyzed using an interpretive method. Results. The barriers to adherence to self-management included ageing-related physical and psychological changes, restrictions related to specific cultural factors, lack of self-discip...
Age-Related Change in Visual, Spatial, and Verbal Memory
2006-01-01
Objectives: To explore the relationship between age and performance on verbal, visual and spatial memory tasks and to examine whether verbal, visual and spatial memory can be measured as separate memory representations.Methods: Sixty-two participants aged between 18 and 57 years completed a listening span task, a dot memory task, and an irregular polygon with articulatory suppression task.Results: Verbal and spatial memory declined with increased age. The relationship between age and visual memory, although negative, was not significant. Age correlated with verbal memory to a greater degree than with visual or spatial memory. The correlations between each of the memory tasks were not significant, suggesting that each task was tapping a distinct type of memory.Conclusions: Verbal, visual and spatial memory appears to be differentially affected by age and should be examined as separate representations. Publisher: Australia: Wiley Blackwell Relation: Australasian Journal on Ageing Other identifier: URN:ISSN:1440-6381; URN:ISSN:1741-6612
The Ubiquitous Conserved Glycopeptidase Gcp Prevents Accumulation of Toxic Glycated Proteins
Full Text Available.Amadori-modified proteins (AMPs) are the products of nonenzymatic glycation formed by reaction of reducing sugars with primary amine-containing amino acids and can develop into advanced glycated end products (AGEs), highly stable toxic compounds. AGEs are known to participate in many age-related human diseases, including cardiovascular, neurological, and liver diseases. The metabolism of these glycated proteins is not yet understood, and the mechanisms that reduce their accumulation are not known so far. Here, we show for Escherichia coli that a conserved glycopeptidase (Gcp, also called Kae1), which is encoded by nearly every sequenced genome in the three domains of life, prevents the accumulation of Amadori products and AGEs. Using mutants, we show that Gcp depletion results in accumulation of AMPs and eventually leads to the accumulation of AGEs. We demonstrate that Gcp binds to glycated proteins, including pyruvate dehydrogenase, previously shown to be a glycation-prone enzyme. Our experiments also show that the severe phenotype of Gcp depletion can be relieved under conditions of low intracellular glycation. As glycated proteins are ubiquitous, the involvement of Gcp in the metabolism of AMPs and AGEs is likely to have been conserved in evolution, suggesting a universal involvement of Gcp in cellular aging and explaining the essentiality of Gcp in many organisms.
THE ROLE OF PROTEOLYTIC CELLULAR SYSTEMS IN TRABECULAR MESHWORK HOMEOSTASIS
2009-04-01
Full Text Available.The molecular mechanisms contributing to the progressive malfunction of the trabecular meshwork (TM)/Schlemm’s canal (SC) conventional outflow pathway during aging and in Primary Open Angle Glaucoma (POAG) are still poorly understood. Progressive accumulation of damaged and cross-linked proteins is a hallmark of aging tissues and has been proposed to play a major role in the tissue abnormalities associated with organismal aging and many age-related diseases. Such progressive accumulation of damaged proteins with age is believed to result from both, increased oxidative stress that results in faster rates of protein damage, as well as from a functional decline in the cellular proteolytic machinery that eliminates misfolded and damaged proteins. Here, we review the reported data that supports the occurrence of oxidative damage and the alterations in the intracellular proteolytic systems in the TM in aging and POAG. Finally, we discuss how the functional decline of the cellular proteolytic machinery in the TM might lead to the observed physiologic alterations of the outflow pathway in glaucoma.
THE ROLE OF PROTEOLYTIC CELLULAR SYSTEMS IN TRABECULAR MESHWORK HOMEOSTASIS
The molecular mechanisms contributing to the progressive malfunction of the trabecular meshwork (TM)/Schlemm’s canal (SC) conventional outflow pathway during aging and in Primary Open Angle Glaucoma (POAG) are still poorly understood. Progressive accumulation of damaged and cross-linked proteins is a hallmark of aging tissues and has been proposed to play a major role in the tissue abnormalities associated with organismal aging and many age-related diseases. Such progressive accumulation of damaged proteins with age is believed to result from both, increased oxidative stress that results in faster rates of protein damage, as well as from a functional decline in the cellular proteolytic machinery that eliminates misfolded and damaged proteins. Here, we review the reported data that supports the occurrence of oxidative damage and the alterations in the intracellular proteolytic systems in the TM in aging and POAG. Finally, we discuss how the functional decline of the cellular proteolytic machinery in the TM might lead to the observed physiologic alterations of the outflow pathway in glaucoma.
2010-01-01
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons (MNs) that causes skeletal muscle paralysis. Familial forms of ALS are linked to mutations in the superoxide dismutase-1 (SOD1) gene. The mechanisms of human SOD1 (hSOD1) toxicity to MNs are unknown. We hypothesized that skeletal muscle is a primary site of pathogenesis in ALS that triggers MN degeneration. We created transgenic (tg) mice expressing wild-type-, G37R- and G93A-hSOD1 gene variants only in skeletal muscle. These tg mice developed age-related neurologic and pathologic phenotypes consistent with ALS. Affected mice showed limb weakness and paresis with motor deficits. Skeletal muscles developed severe pathology involving oxidative damage, protein nitration, myofiber cell death and marked ne...
2000-10-01
With the recent creation of the PX HE Core Surveillance Database, individual specimen surveillance values can be easily compared to the corresponding individual qualification values to evaluate for trends. A review of the data shows a broad scatter in measured stress-strain values. Using the available HE surveillance database, it is clear that the surveillance measurements from the two Cycle 15 charges fall within the range of qualification stress and strain values recorded previously for PBX 9502 lots and that no apparent stockpile-age related trends are evident in the tensile stress-strain data. As a result of this investigation, some changes are being made to the core surveillance specifications to minimize the effects on tensile data scatter due to temperature and humidity differences and method to method changes. These data analyses do point out the need for a comprehensive understanding of the effect of a number of variables, i.e. formulation and pressing method, density, stockpile age, lot-to-lot variations, temperature, and humidity on the mechanical property behavior of HE composite materials. Too often data have been compared without the relevant details made available to determine if the test conditions were nominally the same or different. These results also point out the critical need to establish useful stress-strain limits for qualification and surveillance testing of HEs.
Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice
2010-05-01
Full Text Available.Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.
Circulating endothelial progenitor cells: a new approach to anti-aging medicine?
Full Text Available.Endothelial dysfunction is associated with major causes of morbidity and mortality, as well as numerous age-related conditions. The possibility of preserving or even rejuvenating endothelial function offers a potent means of preventing/treating some of the most fearful aspects of aging such as loss of mental, cardiovascular, and sexual function.Endothelial precursor cells (EPC) provide a continual source of replenishment for damaged or senescent blood vessels. In this review we discuss the biological relevance of circulating EPC in a variety of pathologies in order to build the case that these cells act as an endogenous mechanism of regeneration. Factors controlling EPC mobilization, migration, and function, as well as therapeutic interventions based on mobilization of EPC will be reviewed. We conclude by discussing several clinically-relevant approaches to EPC mobilization and provide preliminary data on a food supplement, Stem-Kine, which enhanced EPC mobilization in human subjects.
2010-01-01
In this study we examined whether the levels of gene expressions of the three b- adrenergic receptor (bAR) subtypes, b1, b2, and b3, contribute to age-related increase in bAR density. Liver membranes and total RNA were prepared from young (4- to 6-month-old) and old (24-month-old) male Fischer 344 rats. bAR density (Bmax) in liver membranes was measured by a radioligand receptor binding assay using the receptor subtype nonselective bAR antagonist 125I-pindolol as the radioligand. Steady-state levels of b2AR mRNA in rat liver were measured by Northern blot analysis; because of the low abundance of b1AR and b3AR mRNA in rat liver, the expressions of these genes were measured by a semiquantitative RT-PCR or an RT-PCR. Scatchard analysis of saturation binding curves of the binding assay confir...
Age-related changes in pro-opiomelanocortin (POMC) and related receptors in human epidermis
2010-01-01
Synopsis Much effort has been placed in cosmetic research for better understanding of the effects of ageing on skin's appearance, structure, mechanical properties and function. It is now of common knowledge that UV radiations induce pre-mature skin ageing notably in the epidermis where UV radiations induce keratinocyte differentiation. As UV radiations have also been shown to regulate the pro-opiomelanocortin (POMC) peptide family in the skin and because no study has been conducted so far to investigate the age-related changes in POMC and related receptors, we analysed POMC, MC-1R, MC-2R and MOR-1 at mRNA level and MC-1R, MC-2R and MOR-1 at protein level too in primary cultures of normal human keratinocytes obtained from female donors aged from 17 to 75 years old. Regarding the gene expres...
A statistical analysis of acoustic emission signals for tool condition monitoring (TCM)
2003-12-27
The statistical properties of acoustic emission signals for tool condition monitoring (TCM) applications in mechanical lathe machining are analyzed in this paper. Time series data and root mean square (RMS) values at various tool wear levels are shown to exhibit features that can be put into relation with ageing in both cases. In particular, the histograms of raw data show power-law distributions above a cross-over value, in which newer cutting tools exhibit more numerous larger events compared with more worn-out ones. For practical purposes, statistics based on RMS values are more feasible, and the analysis of these also reveals discriminating age-related features. The assumption that experimental RMS histograms follow a Beta (b) distribution has also been tested. The residuals of the modeling b functions indicate that the search for a more appropriate fitting function for the experimental distribution is desirable.
Parallel Analysis of Gene Expression: Bone Cells as a Model System
2005-01-01
The use of comparative gene expression techniques has expanded considerably in recent years, especially with advances in microarray technology. In this project, a number of these techniques have been used to identify genes worthy of further research as potential mediators of bone cell differentiation and function. Bone is a tissue with many potential as yet unidentified regulatory molecules. The skeleton is constantly undergoing replacement, with old bone being degraded by osteoclasts, bone resorbing cells derived from the haematopoietic lineage, and replaced with new bone by osteoblasts, bone synthesizing cells derived from the mesenchymal stem cell lineage. When the rate of bone resorption exceeds the rate of bone synthesis, osteoporosis can occur. Osteoporosis is the most common form of disease affecting the skeleton, and one of the most common age-related diseases, and is a major social and economic burden. Recent studies have shown that cells of mesenchymal lineage are capable of adopting alternate differentiation fates, suggesting that cell-based therapies may be a useful therapeutic approach for this disease. Therefore, identification of molecular mechanisms involved in regulating the behavior and development of bone forming and bone resorbing cells is essential. The aim of this project, therefore, was to identify genes involved in various stages of bone cell differentiation using comparative gene expression techniques. The specific objectives of this project became: 1) to identify molecules expressed by osteoblasts which may increase or decrease bone synthesis; these may have potential for exploitation to treat bone loss in osteoporosis, or excess bone deposition in osteopetrosis; and 2) to identify molecules expressed by osteoclasts which may increase or decrease bone resorption; these may have potential for exploitation to treat excess bone deposition in osteopetrosis, or bone loss in osteoporosis. The first objective, identification of molecules expressed by osteoblasts involved in bone deposition, was addressed using three techniques: subtractive hybridization, DNA microarray analysis, and DNA macroarray analysis. These techniques were used to identify genes transcribed at different levels between foetal osteoblasts and fibroblasts. The key difference between DNA arrays, and subtractive hybridization, as techniques is that DNA arrays utilize a cDNA population fixed to a rigid medium as starting material. This means, therefore, that in order to identify a gene as being expressed, the gene must be present on the array, as a member of the cDNA library the original starting array was made from. This inhibits identification of truly novel transcripts, a bias which is removed in techniques such as subtractive hybridization. The technique of subtractive hybridization is used to identify genes transcribed at higher levels in one DNA sample compared with another. The subtractive hybridization technique described here was modified to enrich a foetal osteoblast phagemid library by removing phagemid which contain transcripts common to foetal osteoblasts and dermal fibroblasts, thus resulting in identification of genes expressed uniquely or at higher levels in osteoblasts. The technique identified 65 genes that were expressed either highly or specifically in osteoblasts when compared with fibroblasts. Some of the genes identified were found in multiple library clones, such as collagen and fibronectin, both of which are key structural components of bone, abundantly expressed by osteoblasts. Expression of some other identified genes had not previously been detected in osteoblasts, making them interesting targets for further investigation. Interesting genes revealed using this technique included prohibitin, leptin-receptor gene related protein, ornithine decarboxylase antizyme, amyloid precursor peptide and connective tissue growth factor. The usefulness of the technique was verified by performing real-time PCR to confirm the expression of these genes either specifically or abundantly in osteoblast cells. DNA array analysis was undertaken to identify transcripts previously identified in other tissues, but not investigated in bone cells to date. Micro and macroarray analysis was used to identify known genes that were over or underexpressed. The microarray comparison of fibroblasts and osteoblasts using cDNA differentially labeled with fluorescent dyes hybridized to glass microarrays, showed that the two cell types were very similar, with just 64 genes found to be regulated 5-fold or more- 37 were down-regulated in osteoblasts, and 27 were upregulated in osteoblasts, out of the 19,000 genes represented on the array. Genes shown to be significantly upregulated in osteoblasts by the 19k microarray included several neural proteins and transcription factors, while genes downregulated in osteoblasts included cell signal transducers and other transcriptional activity modifiers. The set of Atlas cDNA arrays consists of three pairs of arrays, with each pair containing 1176 genes. Two pairs of filters, or 2352 genes, were probed in the osteoblast/fibroblast comparison, while all three pairs, or 3528 genes, were probed in the osteoclast/macrophage comparison. The data from the DNA macroarray experiment, in which radioactively-labelled cDNA from osteoblasts and fibroblasts was hybridized to two separate sets of nylon arrays (ATLAS human cDNA arrays) showed that 12 out of the 2352 genes assayed were significantly regulated, with eight upregulated in osteoblasts, and four downregulated in osteoblasts. Genes upregulated in osteoblasts included transcription factor Dp-2, cAMP response element binding protein 1, and transcription factor ATF2. Genes down-regulated in osteoblasts included teratocarinoma derived growth factor, thymosin beta-10, and transcription factor 3. To address the second objective, and identify molecules expressed by osteoclasts involved in bone resorption, the DNA macroarray analysis approach was repeated. cDNA isolated from osteoclasts was compared with cDNA isolated from macrophages to identify genes differentially transcribed between these two cell types which differentiate from the same developmental lineage in vitro. DNA macroarray analysis, performed using radioactively labeled cDNA from osteoclasts and macrophages hybridized to ATLAS human cDNA arrays identified 53 genes as upregulated in osteoclasts, including GM-CSF Receptor, signalling molecule calmodulin 1, and transcription regulatory molecule Nuclear Factor of Activated T-cells (NFAT). Seventeen genes were shown to be downregulated in osteoclasts, including transcription factor zpf36, Integrin 5, and X-ray repair complementing protein. The studies described here suggested that osteoclasts and macrophages have more differentially expressed genes than osteoblasts and fibroblasts, with 1.98% of genes arrayed showing differential expression between osteoclasts and macrophages, but only 0.3% of genes arrayed showing differential expression between fibroblasts and osteoblasts. This suggests that the morphological differences between cell types may be a direct reflection of the molecular differences between them as well, as osteoblasts and fibroblasts are quite similar, while osteoclasts and macrophages are morphologically quite distinct. From this project, it would appear that comparisons of different populations of cells require the use of different techniques to yield the best results, and that the techniques of array analysis and subtractive hybridization may be best utilized in combination, rather than exclusively of each other. Many of the genes identified as differentially expressed between fibroblasts and osteoblasts using DNA arrays were fairly well-characterised 'house-keeping' type genes- metabolic, structural, and not specific or likely to play a significant role in the differentiation of osteoblasts, or the development of bone disease. One possible reason for this is that the arrays are too limited by the number of genes featured, to be able to detect many differences between similar cell types, where there are fewer differences to detect. In contrast, using the same macroarrays to compare the more distinct osteoclasts and macrophages resulted in identification of several interesting candidate genes, showing that some cell type comparisons can be performed adequately using this technology. By using the subtractive hybridization method to enrich a pre-existing phagemid library, any bias related to the genes able to be detected was removed. Although this technique requires manufacture of a cDNA library of the cell type of interest, it may be worthwhile for the comparison of similar cell types where sensitivity is an issue. In summary, this project used the techniques of subtractive hybridization and DNA macroarray and microarray analysis to detect genes showing differential expression between osteoblasts and fibroblasts, and used DNA macroarray analysis to detect genes differentially expressed between osteoclasts and macrophages. Of particular note were results for two interesting genes, amyloid precursor protein and ornithine decarboxylase antizyme. Amyloid Precursor Protein was identified as expressed in high levels in osteoblasts by subtractive hybridization, and real-time PCR studies later confirmed that it is expressed specifically in osteoblasts, and not at all in fibroblasts. Differential expression of ornithine decarboxylase antizyme was identified between both osteoclasts and macrophages, and fibroblasts and osteoblasts. Expression of antizyme results in destruction of ornithine decarboxylase, which is required for the production of polyamines. Degrading cells release spermidine, a polyamine, which attracts macrophages. It is possible that differential regulation of the inhibitory antizyme may be an important distinction between the function of macrophages as general tissue and debris scavenging cells, and osteoclasts, which specifically degrade bone. This study has identified some genes which further studies may show to be important regulators of cellular differentiation and behaviour. Publisher: Griffith University. School of Health Science Language: en Rights: http://www.gu.edu.au/disclaimer.html); Copyright Wendy Elizabeth Simcock
Morphological studies of the vestibular nerve
The anatomy of the intratemporal part of the vestibular nerve in man, and the possible age related degenerative changes in the nerve were studied. The form and structure of the vestibular ganglion ...
... foods at most meals. Fiber and Diverticular Disease Diverticulitis, an inflammation of the intestine, is one of the most common age-related disorders of the colon in Western society. In North America, this painful ...
Ageing and the auditory system
2006-03-01
There are a number of pathophysiological processes underlying age related changes in the auditory system. The effects of hearing loss can have consequences beyond the immediate loss of hearing, and...Full Text Available
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