Mature age job seekers: the role of proactivity

Purpose In the context of demographic and economic changes, helping mature age job seekers find employment is imperative. The purpose of this paper is to examine mature age job seekers’ proactive personality as a moderator of the relationship between age and job search intensity; and to examine job search self-efficacy as a mediator of this moderation effect. It was hypothesized that the generally negative relationships between age and job search self-efficacy and intensity are weaker among job seekers with a more proactive personality. Design/methodology/approach In total, 188 job seekers between 40 and 64 years completed an online questionnaire. Data were analyzed using structural equation modeling. Findings Consistent with previous research, age was negatively related to job search intensity. Proactive personality was positively related to job search intensity and moderated the relationship between age and job search intensity. Extending previous research, proactive personality also positively predicted job search self-efficacy and moderated the relationship between age and job search self-efficacy which, in turn, positively predicted job search intensity. Research limitations/implications Potential limitations of the study include the cross-sectional design, sample selectivity, and the omission of possibly important control variables. Practical implications Practitioners, organizations, and societies concerned with helping mature age job seekers find employment could provide additional support to those with a less proactive personality and low job search self-efficacy. Originality/value This study extends previous research by showing that mature age job seekers’ job search self-efficacy mediates the moderating effect of proactive personality on the relationship between age and job search intensity.

Development of a cultured tissue substitute to repair the ageing retina

This project provides a foundation for the use of silk membranes in a tissue engineered therapy for the treatment of devastating retinal diseases such as age-related macular degeneration. The three-dimensional tissue model described in this thesis has great potential for use in basic research of retinal pathologies, and the potential to be implemented into clinical approaches after appropriate refinement.

Effect of DNA extraction on ageing success in coral trout (Plectropomus leopardus) otoliths

To maximize the information commonly collected from otoliths, the effect of DNA extraction on the estimation of age with otoliths was evaluated by comparing sagittal otolith samples from common coral trout (Plectropomus leopardus) for clarity and ageing discrepancies in DNA-extracted and untreated control otoliths. The DNA extraction process had no significant effect, indicating that archived otoliths can be used as a source of DNA while retaining their utility for age estimation.

The role of advanced glycation end products in retinal ageing and disease

The retina is exposed to a lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes. Retinal ageing is complex and a raft of abnormalities can accumulate in all layers of the retina. Some of this pathology serves as a sinister preamble to serious conditions such as age-related macular degeneration (AMD) which remains the leading cause of irreversible blindness in the Western world.

The formation of advanced glycation end products (AGEs) is a natural function of ageing but accumulation of these adducts also represents a key pathophysiological event in a range of important human diseases. AGEs act as mediators of neurodegeneration, induce irreversible changes in the extracellular matrix, vascular dysfunction and pro-inflammatory signalling. Since many cells and tissues of the eye are profoundly influenced by such processes, it is fitting that advanced glycation is now receiving considerable attention as a possible pathogenic factor in visual disorders.

This review presents the current evidence for a pathogenic role for AGEs and activation of the receptor for AGEs (RAGE) in initiation and progression of retinal disease. It draws upon the clinical and experimental literature and highlights the opportunities for further research that would definitively establish these adducts as important instigators of retinal disease. The therapeutic potential for novel agents that can ameliorate AGE formation of attenuate RAGE signalling in the retina is also discussed.

Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

Saccharomyces Cerevisiae as a biotechnological tool for ageing research:studies on translation and metabolism

The yeast Saccharomyces cerevisiae is an important model organism for the study of cell biology. The similarity between yeast and human genes and the conservation of fundamental pathways means it can be used to investigate characteristics of healthy and diseased cells throughout the lifespan. Yeast is an equally important biotechnological tool that has long been the organism of choice for the production of alcoholic beverages, bread and a large variety of industrial products. For example, yeast is used to manufacture biofuels, lubricants, detergents, industrial enzymes, food additives and pharmaceuticals such as anti-parasitics, anti-cancer compounds, hormones (including insulin), vaccines and nutraceuticals. Its function as a cell factory is possible because of the speed with which it can be grown to high cell yields, the knowledge that it is generally recognized as safe (GRAS) and the ease with which metabolism and cellular pathways, such as translation can be manipulated. In this thesis, these two pathways are explored in the context of their biotechnological application to ageing research: (i) understanding translational processes during the high-yielding production of membrane protein drug targets and (ii) the manipulation of yeast metabolism to study the molecule, L-carnosine, which has been proposed to have anti-ageing properties. In the first of these themes, the yeast strains, spt3?, srb5?, gcn5? and yTHCBMS1, were examined since they have been previously demonstrated to dramatically increase the yields of a target membrane protein (the aquaporin, Fps1) compared to wild-type cells. The mechanisms underlying this discovery were therefore investigated. All high yielding strains were shown to have an altered translational state (mostly characterised by an initiation block) and constitutive phosphorylation of the translational initiation factor, eIF2a. The relevance of the initiation block was further supported by the finding that other strains, with known initiation blocks, are also high yielding for Fps1. A correlation in all strains between increased Fps1 yields and increased production of the transcriptional activator protein, Gcn4, suggested that yields are subject to translational control. Analysis of the 5´ untranslated region (UTR) of FPS1 revealed two upstream open reading frames (uORFs). Mutagenesis data suggest that high yielding strains may circumvent these control elements through either a leaky scanning or a re-initiation mechanism. In the second theme, the dipeptide L-carnosine (ß-alanyl-L-histidine) was investigated: it has previously been shown to inhibit the growth of cancer cells but delay senescence in cultured human fibroblasts and extend the lifespan of male fruit flies. To understand these apparently contradictory properties, the effects of L-carnosine on yeast were studied. S. cerevisiae can respire aerobically when grown on a non-fermentable carbon source as a substrate but has a respiro-fermentative metabolism when grown on a fermentable carbon source; these metabolisms mimic normal cell and cancerous cell metabolisms, respectively. When yeast were grown on fermentable carbon sources, in the presence of L-carnosine, a reduction in cell growth and viability was observed, which was not apparent for cells grown on a non-fermentable carbon source. The metabolism-dependent mechanism was confirmed in the respiratory yeast species Pichia pastoris. Further analysis of S. cerevisiae yeast strains with deletions in their nutrient-sensing pathway, which result in an increase in respiratory metabolism, confirmed the metabolism-dependent effects of L-carnosine.

The interconnectedness of ageing:does the convoy principal apply?

This is an excerpt from the content: The convoy principal states that any system is only as functional as its ‘slowest’ unit. As organisms are made up of interconnected networks of physiological systems, it is possible that this principle applies to the biology of ageing. Often biogerontology will focus either on organismal ageing (mechanisms associated with increased longevity of a lower model organism for example), ageing of an individual organ system (such as the cardiovascular/musculoskeletal/immune) or ageing at the cellular level (from telomere length to cellular senescence, with many different cell types being studied) without considering the interconnectedness between the three and importantly, between the separate units of the convoy; the different organ systems. Conceptually, research that aims to identify ‘anti-ageing’ therapies is often deemed to be reaching for a panacea that will arrest or slow down the ageing process as a whole, whereas a more realistic aim is to first identify how we can improve the perfor ...

Intracellular redox state modulates the T cell surface proteome – relevance to ageing

During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Here we describe the effects of depleting intracellular glutathione concentration for T cell exofacial expression of thioredoxin 1 and IL-2 production, and have determined the distribution of Trx1 with ageing. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show using Western blotting that cell surface thioredoxin-1 is lowered and that the response to the lectin phytohaemagglutinin measured by ELISA as IL-2 production is also decreased. Using flow cytometry we show that the distribution of Trx1 on primary CD4+ T cells is age-dependent, with lower surface Trx1 expression and greater variability of surface expression observed with age. Together these data suggest that a relationship exists between the intracellular redox compartment and exofacial surface. Redox imbalance may be important for impaired T cell function during ageing.

The ageing of alumina hydrolysates synthesized from sec-butoxyaluminium(III)

A combination of X-ray diffraction, thermal analysis and Raman spectroscopy was employed to characterise the ageing of alumina hydrolysates synthesised from the hydrolysis of anhydrous tri-sec-butoxyaluminium(III). X-Ray diffraction showed that the alumino-oxy(hydroxy) hydrolysates were pseudoboehmite. For boehmite the lamellar spacings are in the b direction and multiple d(020) peaks are observed for the un-aged hydrolysate. After 4 h of ageing, a single d(020) peak is observed at 6.53 Å. Thermal analysis showed five endotherms at 70, 140, 238, 351 and 445°C. These endotherms are attributed to the dehydration and dehydroxylation of the boehmite-like hydrolysate. Raman spectroscopy shows the presence of bands for the washed hydrolysates at 333, 355, 414, 455, 475, 495, 530 and 675 cm–1. These bands are attributed to pseudoboehmite. Ageing of the hydrolysates results in an increase in the crystallite size of the pseudoboehmite.