Socioeconomic status, psychosocial stress, and cellular ageing

Health varies with social class, and people in affluent sectors of society generally live longer and remain healthier than less privileged groups. Socioeconomic inequalities in health have become a major concern to health professionals and the public at large. There is an urgent need to understand how social factors are translated into disease risk. Psychosocial factors such as job stress, financial strain, social isolation and depression also contribute to risk of physical illness, and are more common in adults of lower socioeconomics status. It is possible that lower social status and exposure to chronic life stress stimulate faster ageing, and that this is one reason why they contribute to disease risk. Our project will test the hypothesis that lower socioeconomic position and chronic life stress lead to more rapid biological ageing by measuring the telomeres in the nuclei of cells. This is an interdisciplinary collaboration involving epidemiology, psychology and cell biology. The study will involve middle aged and older men and women who are part of the Whitehall II epidemiological cohort, a sample of British Civil servants who have been monitored for the part 20 years by Professor Marmot and his research group. They will have their telomeres measured, and assessments will be made of their cardiovascular and inflammatory responses to stress, subclinical cardiovascular disease, and oxidative stress. We expect that lower socioeconomic position and life stress will be related to a level of cellular ageing characteristic of an older person, and that these effects will be related to greater inflammatory stress responses. The study will deepen our understanding of the biological pathways through which life experience influences physical health, while pointing to new preventive and therapeutic avenues that might be explored in order to reduce socioeconomic health inequalities in the future.

Lower socioeconomic status (SES) and chronic psychosocial stress are associated with a range of adverse health outcomes, including coronary heart disease, type 2 diabetes and onset of disability. One reason may be that lower SES and chronic stress accelerate biological ageing. Telomerase activity and telomere length are markers of cellular ageing. This study will test the hypothesis that lower SES and psychosocial adversity (chronic stress and low social resources) are associated with reduced telomerase activity and shorter telomeres independently of chronological age. Our study will also investigate mediating mechanisms, predicting that lower SES and psychosocial adversity are related to oxidative stress and to heightened inflammatory responses to stress.

These hypotheses will be tested in a study currently in progress involving 660 men and women aged 58-72 years recruited from the Whitehall II epidemiological cohort. Participants are being systematically sampled by SES to compare higher, intermediate and lower status groups. Each person undergoes laboratory psychophysiological testing in which biological responses to standardised challenges are assessed. Blood pressure, heart rate variability, cortisol, lipids, C-reactive protein, interleukin (IL) 6 and IL-1a, and fibrinogen stress responsivity are recorded. Measures of chronic stress exposure (e.g. financial strain, marital conflict, family stress), social relationships (social support, networks, neighbourhood cohesion), psychological factors (e.g. depression, hostility, optimism) and lifestyle are being obtained. All participants undergo electron beam computed tomography (EBCT) for the assessment of coronary artery calcification as a marker of subclinical coronary disease.

This application is for funding to add the collection and analysis of peripheral blood mononuclear cells to the protocol so as to assess telomerase activity and telomere length, together with measures of oxidative stress and chemokines (MCP-1 and RANTES). These variables will allow us to discover whether SES differences in cellular ageing are present, and whether differences are associated with heightened oxidative stress and inflammatory stress responses, with subclinical coronary disease and with psychosocial adversity. The addition of these assessments to an existing study will permit these issues to be investigated at relatively low cost. Involvement of the Whitehall II cohort will ensure that participants are well characterised in terms of clinical, psychosocial and biological risk, and that disease incidence will be tracked into the future. The results will deepen our understanding of the impact of social and psychological factors on physiological function and physical disease risk, opening new avenues for prevention.