The effects of aging on the BTBR mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer`s disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer`s disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57BI/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n = 10 per group) were submitted to an acquisition session, reinforcement to learning (24 h later: test 1) and final test (7 days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8 +/- 2.3%; 6mo: 4.1 +/- 0.6%; 12mo: 2.2 +/- 0.6%, 18mo: 3.6 +/- 0.6%, P < 0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P < 0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P < 0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P < 0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. (C) 2009 Elsevier Ltd. All rights reserved.

The Aging Process of the Heart: Obesity Is the Main Risk Factor for Left Atrial Enlargement During Aging The MONICA/KORA (Monitoring of Trends and Determinations in Cardiovascular Disease/Cooperative Research in the Region of Augsburg) Study

Objectives This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods Participants (1,212 men and women, age 25 to 74 years) originated from a sex-and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA >= 35.7 and >= 33.7 ml/m in men and women, respectively. Results At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level. (J Am Coll Cardiol 2009; 54: 1982-9) (C) 2009 by the American College of Cardiology Foundation

Effect of aging on the stability of ceramic foams prepared by thermostimulated sol-gel process

This work presents a new route of preparation of zirconium ceramic foams based on the thermostimulated sol-gel process. This method produces gelled bodies with up to 90% of porosity in the wet gel and can be used to make complex-shaped components. Unfortunately, the shrinkage during the drying step allows to a catastrophic reduction (50%) of the foam porosity. To improve the foam stability we carried out a systematic study of the effect of gel foam aging on the drying process. Samples were aged in closed vessel at 25 C during different time period (from 6 to 240 h). The shrinkage and the mass loss during drying at 50 C were measured in situ, using a non-contact technique performed with a special apparatus. The results show that the total linear shrinkage decreases from 46% to 8% as the aging period increase from 6 to 240 h. This behavior is followed by a small change of total mass loss, from 42 to 54%. It indicates that by aging the structural stiffness of the foams increases due to secondary condensation reactions. Thus, by controlling the aging period, the porosity can be increased from 67 to 75% and the average size of mesopores of dried foams can be screened from 0.3 to 0.9 mum. Finally, these results demonstrate that the thermostimulated sol-gel transition provides a potential route to ceramic foams manufacture.

A multistep process of cancer associated fibroblasts determination under CSL-p53 control

Stromal fibroblast senescence has been linked to the aging-associated increase of tumors. However, in epithelial cancer, density and proliferation of cancer associated fibroblasts (CAF) are frequently increased, rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-JK in dermal fibroblasts is sufficient for CAF activation with consequent development of keratinocyte-derived tumors. We show here that CSL silencing induces senescence of primary fibroblasts from dermis, oral mucosa, breast and lung. CSL functions in these cells as direct repressor of multiple senescence- and CAF-effector genes. It also physically interacts with p53, repressing its activity. CSL is down-modulated in stromal fibroblasts of premalignant skin actinic keratosis lesions and squamous cell carcinomas (SCC), while p53 gene expression and function is down-modulated only in the latter, with paracrine influences of incipient cancer cells as a likely culprit. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances CAF effector gene expression and promotes stromal and cancer cell expansion. The findings support a CAF activation/stromal co-evolution model under convergent CSL/p53 control of likely clinical relevance.

Effect of aging and oral tolerance on dendritic cell function

Oral tolerance can be induced in some mouse strains by gavage or spontaneous ingestion of dietary antigens. In the present study, we determined the influence of aging and oral tolerance on the secretion of co-stimulatory molecules by dendritic cells (DC), and on the ability of DC to induce proliferation and cytokine secretion by naive T cells from BALB/c and OVA transgenic (DO11.10) mice. We observed that oral tolerance could be induced in BALB/c mice (N = 5 in each group) of all ages (8, 20, 40, 60, and 80 weeks old), although a decline in specific antibody levels was observed in the sera of both tolerized and immunized mice with advancing age (40 to 80 weeks old). DC obtained from young, adult and middle-aged (8, 20, and 40 weeks old) tolerized mice were less efficient (65, 17 and 20%, respectively) than DC from immunized mice (P < 0.05) in inducing antigen-specific proliferation of naive T cells from both BALB/c and DO11.10 young mice, or in stimulating IFN-g, IL-4 and IL-10 production. However, TGF-β levels were significantly elevated in co-cultures carried out with DC from tolerant mice (P < 0.05). DC from both immunized and tolerized old and very old (60 and 80 weeks old) mice were equally ineffective in inducing T cell proliferation and cytokine production (P < 0.05). A marked reduction in CD86+ marker expression was observed in DC isolated from both old and tolerized mice (75 and 50%, respectively). The results indicate that the aging process does not interfere with the establishment of oral tolerance in BALB/c mice, but reduces DC functions, probably due to the decline of the expression of the CD86 surface marker.

Gender-dependent effects of aging on the kidney

It is well known that the kidney plays an important role in the development of cardiovascular diseases such as hypertension. The normal aging process leads to changes in kidney morphology, hemodynamics and function, which increase the incidence of cardiovascular events in the elderly population. These disturbances are influenced by several factors, including gender. In general, females are protected by the effects of estrogens on the cardiorenal system. Several studies have demonstrated the beneficial effects of estrogens on renal function in the elderly; however, the relationships between androgens and kidney health during one’s lifetime are not well understood. Sex steroids have many complex actions, and the decline in their levels during aging clearly influences kidney function, decreases the renal reserve and facilitates the development of cardiovascular disorders. Therefore, in this review, we discuss the cellular, biochemical, and molecular mechanisms by which sex hormones may influence renal function during the aging process.

Healing process of dog dental pulp after pulpotomy and pulp covering with mineral trioxide aggregate or Portland cement.

Considering several reports about the similarity between the chemical compositions of the mineral trioxide aggregate (MTA) and Portland cement (PC), the subject of this investigation was to analyze the behavior of dog dental pulp after pulpotomy and direct pulp protection with these materials. After pulpotomy, the pulp stumps of 26 roots of dog teeth were protected with MTA or PC. Sixty days after treatment, the animal was sacrificed and the specimens removed and prepared for histomorphological analysis. There was a complete tubular hard tissue bridge in almost all specimens. In conclusion, MTA and PC show similar comparative results when used in direct pulp protection after pulpotomy.

Molecular characterization of the human gut microbiota: the effect of aging

Age-related physiological changes in the gastrointestinal tract, as well as modification in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota. The study presented here is focused on the application and comparison of two different microarray approaches for the characterization of the human gut microbiota, the HITChip and the HTF-Microb.Array, with particular attention to the effects of the aging process on the composition of this ecosystem. By using the Human Intestinal Tract Chip (HITChip), recently developed at the Wageningen University, The Netherland, we explored the age-related changes of gut microbiota during the whole adult lifespan, from young adults, through elderly to centenarians. 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 of facultative anaerobes. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammation status, also known as inflamm-aging, as determined by a range of peripheral blood inflammatory markers. In parallel, we overtook the development of our own phylogenetic microarray with a lower number of targets, aiming the description of the human gut microbiota structure at high taxonomic level. The resulting chip was called High Taxonomic level Fingerprinting Microbiota Array (HTF-Microb.Array), and was based on the Ligase Detection Reaction (LDR) technology, which allowed us to develop a fast and sensitive tool for the fingerprint of the human gut microbiota in terms of presence/absence of the principal groups. The validation on artificial DNA mixes, as well as the pilot study involving eight healthy young adults, demonstrated that the HTF-Microb.Array can be used to successfully characterize the human gut microbiota, allowing us to obtain results which are in approximate accordance with the most recent characterizations. Conversely, the evaluation of the relative abundance of the target groups on the bases of the relative fluorescence intensity probes response still has some hindrances, as demonstrated by comparing the HTF.Microb.Array and HITChip high taxonomic level fingerprints of the same centenarians.

Polymeric membranes for CO2 separation: effect of aging, humidity and facilitated transport

Polymeric membranes represent a promising technology for gas separation processes, thanks to low costs, reduced energy consumption and limited waste production. The present thesis aims at studying the transport properties of two membrane materials, suitable for CO2 purification applications. In the first part, a polyimide, Matrimid 5218, has been throughout investigated, with particular reference to the effect of thermal treatment, aging and the presence of water vapor in the gas transport process. Permeability measurements showed that thermal history affects relevantly the diffusion of gas molecules across the membrane, influencing also the stability of the separation performances. Subsequently, the effect of water on Matrimid transport properties has been characterized for a wide set of incondensable penetrants. A monotonous reduction of permeability took place at increasing the water concentration within the polymer matrix, affecting the investigated gaseous species to the same extent, despite the different thermodynamic and kinetic features. In this view, a novel empirical model, based on the Free Volume Theory, has been proposed to qualitatively describe the phenomenon. Moreover, according to the accurate representation of the experimental data, the suggested approach has been combined with a more rigorous thermodynamic tool (NELF Model), allowing an exhaustive description of water influence on the single parameters contributing to the gas permeation across the membrane. In the second part, the study has focused on the synthesis and characterization of facilitated transport membranes, able to achieving outstanding separation performances thanks to the chemical enhancement of CO2 permeability. In particular, the transport properties have been investigated for high pressure CO2 separation applications and specific solutions have been proposed to solve stability issues, frequently arising under such severe conditions. Finally, the effect of different process parameters have been investigated, aiming at the identification of the optimal conditions capable to maximize the separation performance.

Understanding Seniors' Perceptions and Stereotypes of Aging

Research suggests there is a connection between stereotypes, beliefs, and behavior in older individuals. To explore this link of stereotypes affecting beliefs and beliefs affecting behavior, we interviewed young (age 60 to 75) seniors in an effort to further examine these relationships. Semistructured qualitative interviews were conducted with 20 seniors. Questions focused on the broad themes of aging stereotypes and attitudes towards active living. Responses from the participants indicated the variety of opinions and beliefs seniors hold about the aging process. Intriguing results emerged on the topic of role models. Participants often had someone in their lives who represented what it means to age successfully. Generally, this was an individual older than themselves, active, vigorous, and illustrative of the high quality of life that is possible into a very late age. In addition, these individuals provide a direct contrast to the most negative stereotypes of aging.

Effect of aging on yield stress and corrosion resistance of die cast magnesium alloy

Corrosion resistance is an important property that could be affected by the ageing process. In order to investigate whether aging affects the corrosion resistance, corrosion rate and yield strength of diecast magnesium alloy AZ91D were measured and analysed after ageing. It was found that the dependence of the corrosion rate on ageing time can be ascribed to the changes in microstructure of the alloy and chemical composition of its matrix. Precipitation of the P phase (Mg17Al12) occurred along the grain boundaries during the initial ageing stages, resulting in a decreasing corrosion rate and an inceasing yield strength. In the later stages, the decreasing aluminium content in the alpha matrix made it more active, causing an increase in the corrosion rate. The decrease in aluminium content in the matrix also leads to a decrease in yield strength.

EFFECTS OF AGING ON MIDBRAIN AND CORTICAL SPEECH-IN-NOISE PROCESSING

Older adults frequently report that they can hear what they have been told but cannot understand the meaning. This is particularly true in noisy conditions, where the additional challenge of suppressing irrelevant noise (i.e. a competing talker) adds another layer of difficulty to their speech understanding. Hearing aids improve speech perception in quiet, but their success in noisy environments has been modest, suggesting that peripheral hearing loss may not be the only factor in the older adult’s perceptual difficulties. Recent animal studies have shown that auditory synapses and cells undergo significant age-related changes that could impact the integrity of temporal processing in the central auditory system. Psychoacoustic studies carried out in humans have also shown that hearing loss can explain the decline in older adults’ performance in quiet compared to younger adults, but these psychoacoustic measurements are not accurate in describing auditory deficits in noisy conditions. These results would suggest that temporal auditory processing deficits could play an important role in explaining the reduced ability of older adults to process speech in noisy environments. The goals of this dissertation were to understand how age affects neural auditory mechanisms and at which level in the auditory system these changes are particularly relevant for explaining speech-in-noise problems. Specifically, we used non-invasive neuroimaging techniques to tap into the midbrain and the cortex in order to analyze how auditory stimuli are processed in younger (our standard) and older adults. We will also attempt to investigate a possible interaction between processing carried out in the midbrain and cortex.

Unlocking the Potential of Women in the Rural Development Process of Republic of Srpska: The Role of Extension Service

In Bosnia Herzegovina the development of clear policy objectives and endorsement of a long-term, coherent and mutual agricultural and rural development policy have also been affected by structural problems: a lack of reliable information on population and other relevant issues, the absence of an adequate land registry system and cadastre. Moreover in BiH the agricultural and rural sectors are characterized by many factors that have typically affected transition countries such as land fragmentation, lack of agricultural mechanization and outdated production technologies, and rural aging, high unemployment and out-migration. In such a framework the condition and role of women in rural areas suffered for the lack of gender disaggregated data and a consequent poor information that lead to the exclusion of gender related questions in the agenda of public institutions and to the absence of targeted policy interventions. The aim of the research is to investigate the role and condition of women in the rural development process of Republic of Srpska and to analyze the capacity of extension services to stimulate their empowerment. Specific research questions include the status of women in the rural areas of Republic of Srpska, the role of government in fostering the empowerment of rural women, and the role of the extension service in supporting rural women. The methodology - inspired by the case study method developed by R. Yin - is designed along the three specific research questions that are used as building blocks. Each of the three research questions is investigated with a combination of methodological tools - including surveys, experts interviews and focus groups - aimed to overcome the lack of data and knowledge that characterize the research objectives.

Epigenetics of nutrition in aging

There is a need to identify factors that are able to influence health in old age and to develop interventions that could slow down the process of aging and its associated pathologies. Lifestyle modifications, and especially nutrition, appear to be promising strategies to promote healthy aging. Their impact on aging biomarkers has been poorly investigated. In the first part of this work, we evaluated the impact of a one-year Mediterranean-like diet, delivered within the framework of the NU-AGE project in 120 elderly subjects, on epigenetic age acceleration measures assessed with Horvath’s clock. We observed a rejuvenation of participants after nutritional intervention. The effect was more marked in the group of Polish females and in subjects who were epigenetically older at baseline. In the second part of this work, we developed a new model of epigenetic biomarker, based on a gene-targeted approach with the EpiTYPER® system. We selected six regions of interest (associated with ELOVL2, NHLRC1, SIRT7/MAFG, AIM2, EDARADD and TFAP2E genes) and constructed our model through a ridge regression analysis. In controls, estimation of chronological age was accurate, with a correlation coefficient between predicted and chronological age of 0.92 and a mean absolute deviation of 4.70 years. Our model was able to capture phenomena of accelerated or decelerated aging, in Down syndrome subjects and centenarians and offspring respectively. Applying our model to samples of the NU-AGE project, we observed similar results to the ones obtained with the canonical epigenetic clock, with a rejuvenation of the individuals after one-year of nutritional intervention. Together, our findings indicate that nutrition can promote epigenetic rejuvenation and that epigenetic age acceleration measures could be suitable biomarkers to evaluate their impact. We demonstrated that the effect of the dietary intervention is country-, sex- and individual-specific, thus suggesting the need for a personalized approach to nutritional interventions.