Effect of membrane stiffness and cytoskeletal element density on mechanical stimuli within cells: an analysis of the consequences of ageing in cells

A finite element model of a single cell was created and used to investigate the effects of ageing on biophysical stimuli generated within a cell. Major cellular components were incorporated in the model: the membrane, cytoplasm, nucleus, microtubules, actin filaments, intermediate filaments, nuclear lamina, and chromatin. The model used multiple sets of tensegrity structures. Viscoelastic properties were assigned to the continuum components. To corroborate the model, a simulation of Atomic Force Microscopy (AFM) indentation was performed and results showed a force/indentation simulation with the range of experimental results.

Ageing was simulated by both increasing membrane stiffness (thereby modelling membrane peroxidation with age) and decreasing density of cytoskeletal elements (thereby modelling reduced actin density with age). Comparing normal and aged cells under indentation predicts that aged cells have a lower membrane area subjected to high strain compared to young cells, but the difference, surprisingly, is very small and would not be measurable experimentally. Ageing is predicted to have more significant effect on strain deep in the nucleus. These results show that computation of biophysical stimuli within cells are achievable with single-cell computational models whose force/displacement behaviour is within experimentally observed ranges. the models suggest only small, though possibly physiologically-significant, differences in internal biophysical stimuli between normal and aged cells.

Higher effort-reward imbalance and lower job control predict exit from the labour market at the age of 61 years or younger: Evidence from the English Longitudinal Study of Ageing

Background: We examined whether higher effort-reward imbalance (ERI) and lower job control are associated with exit from the labour market. 

Methods: There were 1263 participants aged 50-74 years from the English Longitudinal Study on Ageing with data on working status and work-related psychosocial factors at baseline (wave 2; 2004-2005), and working status at follow-up (wave 5; 2010-2011). Psychosocial factors at work were assessed using a short validated version of ERI and job control. An allostatic load index was formed using 13 biological parameters. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Exit from the labour market was defined as not working in the labour market when 61 years old or younger in 2010-2011. 

Results: Higher ERI OR=1.62 (95% CI 1.01 to 2.61, p=0.048) predicted exit from the labour market independent of age, sex, education, occupational class, allostatic load and depression. Job control OR=0.60 (95% CI 0.42 to 0.85, p=0.004) was associated with exit from the labour market independent of age, sex, education, occupation and depression. The association of higher effort OR=1.32 (95% CI 1.01 to 1.73, p=0.045) with exit from the labour market was independent of age, sex and depression but attenuated to non-significance when additionally controlling for socioeconomic measures. Reward was not related to exit from the labour market. 

Conclusions: Stressful work conditions can be a risk for exiting the labour market before the age of 61 years. Neither socioeconomic position nor allostatic load and depressive symptoms seem to explain this association.

The Sociology of Children, Childhood and Generation

Outlining sociology’s distinctive contribution to childhood studies and our understanding of contemporary children and childhood, The Sociology of Children provides a thought provoking and comprehensive account of the connections between the macro worlds of childhood and the micro worlds of children’s everyday lives.

Examining children’s involvement in areas such as the labour market, family life, education, play and leisure, the book provides an effective balance between understanding childhood as a structural phenomenon, and recognising children as meaning makers actively involved in constructing, co-constructing and reconstructing their everyday lives.

Through the concept of 'generagency' Madeleine Leonard offers a model for examining and illuminating how structure and agency are activated within interdependent relationships influenced by generational positioning. This framework provides a conceptual tool for thinking about the continuities, challenges and changes that impact on how childhood is lived and experienced.

The discrepancy between social isolation and loneliness as a clinically meaningful metric: findings from the Irish and English longitudinal studies of ageing (TILDA and ELSA)

Objective
Scant evidence is available on the discordance between loneliness and social isolation among older adults. We aimed to investigate this discordance and any health implications that it may have.

Method
Using nationally representative datasets from ageing cohorts in Ireland (TILDA) and England (ELSA), we created a metric of discordance between loneliness and social isolation, to which we refer as Social Asymmetry. This metric was the categorised difference between standardised scores on a scale of loneliness and a scale of social isolation, giving categories of: Concordantly Lonely and Isolated, Discordant: Robust to Loneliness, or Discordant: Susceptible to Loneliness. We used regression and multilevel modelling to identify potential relationships between Social Asymmetry and cognitive outcomes.

Results
Social Asymmetry predicted cognitive outcomes cross-sectionally and at a two-year follow-up, such that Discordant: Robust to Loneliness individuals were superior performers, but we failed to find evidence for Social Asymmetry as a predictor of cognitive trajectory over time.

Conclusions
We present a new metric and preliminary evidence of a relationship with clinical outcomes. Further research validating this metric in different populations, and evaluating its relationship with other outcomes, is warranted.

Belief, Knowledge and Expertise. The emergence of the lay expert in medical sociology

The paper has three main aims. First, to trace – through the pages of the Journal – the changing ways in which lay understandings of health and illness have been represented during the 1979-2002 period. Second, to say something about the limits of lay knowledge (and particularly lay expertise) in matters of health and medicine. Third, to call for a re-assessment of what lay people can offer to a democratised and customer sensitive system of health care and to attempt to draw a boundary around the domain of expertise. In following through on those aims, the author calls upon data derived from three current projects. These latter concern the diagnosis of Alzheimer’s disease in people with Down’s syndrome; the development of an outcome measure for people who have suffered a traumatic brain injury; and a study of why older people might reject annual influenza vaccinations. Key words: Lay health beliefs, lay expertise, Alzheimer’s, Traumatic Brain Injury, Vaccinations

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.

Human growth hormone and the temptations of biomedical enhancement

It is likely that humans have sought enhancements for themselves or their children for as long as they have recognised that improvements in individuals are a possibility. One genre of self-improvement in modern society can be called 'biomedical enhancements'. These include drugs, surgery and other medical interventions aimed at improving the mind, body or performance. This paper uses the case of human growth hormone (hGH) to examine the social nature of enhancements. Synthetic hGH was developed in 1985 by the pharmaceutical industry and was approved by the FDA for very specific uses, particularly treatment of growth hormone deficiency. However, it has also been promoted for a number of 'off label' uses, most of which can be deemed enhancements. Drugs approved for one treatment pave the way for use as enhancements for other problems. Claims have been made for hGH as a treatment for idiopathic shortness, as an anti-ageing agent and to improve athletic performance. Using the hGH case, we are able to distinguish three faces of biomedical enhancement: normalisation, repair and performance edge. Given deeply ingrained social and individual goals in American society, the temptations of biomedical enhancements provide inducement for individuals and groups to modify their situation. We examine the temptations of enhancement in terms of issues such as unnaturalness, fairness, risk and permanence, and shifting social meanings. In our conclusions, we outline the potentials and pitfalls of biomedical enhancement.

Constructions of locality and gender and their impact on the educational aspirations of working class children

Over recent years the moral panic that has surrounded 'boys' underachievement' has tended to encourage crude and essentialist comparisons between all boys and all girls and to eclipse the continuing and more profound effects on educational achievement exerted by social class and 'race'/ethnicity. While there are differences in educational achievement between working class boys and girls, these differences are relatively minor when comparing the overall achievement levels of working class children with those from higher, professional social class backgrounds. This paper argues that a need exists therefore for researchers to fully contextualise the gender differences that exist in educational achievement within the over-riding contexts provided by social class and 'race'/ethnicity. The paper provides an example of how this can be done through a case study of 11-year-old children from a Catholic, working class area in Belfast. The paper shows how the children's general educational aspirations are significantly mediated by their experiences of the local area in which they live. However, the way in which the children come to experience and construct a sense of locality differs between the boys and girls and this, it is argued, helps to explain the more positive educational aspirations held by some of the girls compared to the boys. The paper concludes by considering the relevance of locality for understanding its effects on educational aspirations among other working class and/or minority ethnic communities.