Epidemiology of ageing, disability and chronic disease
The Epidemiology and Public Health Group has conducted research into ageing, disability and chronic disease using approaches grounded in genetic epidemiology as well as in social and environmental epidemiology.
Age-related physiological impairment and disease are known to be subject to environmental influences, and there is increasing evidence that they have a significant genetic component. The genetics of ageing has seen extraordinary progress over the last few decades, with animal models suggesting key roles for a limited number of metabolic pathways. Yet humans outlive laboratory specimens many times over, and only evidence from humans can ultimately identify the drivers of human ageing.
The Epidemiology and Public Health group lead a programme of work on identifying candidate genes for ageing, disability and disease in humans, established in collaboration with the Molecular Genetics / Diabetes II group led by Dr Tim Frayling and Prof Andrew Hattersley.
There are a number of approaches to identifying ageing effects of genetic variants. In addition to comparisons of long-lived individuals with those in younger groups, there is increasing interest in using markers of biological age (Barzilai & Shuldiner 2001; Karasik et al. 2005; Martin 2005) and in studying such markers from early old age onward. The Medical School programme is based on this latter approach, supplemented by a strong interest in diabetes and other age-related disease endpoints.
Disease and functional limitations due to major disease have surprisingly high heritability in older people (Leinonen et al. 2005). In fact, many aspects of physical functioning (Carmelli et al. 2000) are strongly heritable in older people. Measured functional impairments have been shown to be a sensitive phenotype for the presence of the ApoE e4 polymorphism in older people (Melzer et al. 2005).
The ageing process, at least in lower organisms, is affected by pathways including insulin and insulin-like growth factor 1 (IGF1) signalling, growth hormone, oxidative damage and lipids. In addition, maintenance and repair of DNA including mitochondrial DNA have proved important. A common response to DNA damage is apoptosis and cell senescence and these responses also appear to affect ageing at the organism level, sharing mechanisms with protection from malignancy.
Prof David Melzer was funded by the National Institutes of Health (Aging Institute) to screen a set of candidate genes for effects on physical and cognitive function in older people.
Social and environmental epidemiology of ageing
In addition to the genetic epidemiology described above, members of the Epidemiology and Public Health Group work on the social and environmental epidemiology of ageing. Work within the group focuses on disabling processes in later life and looks at environmental and other factors associated with the causes of, or delays in, the onset of disability in middle-aged and older adults. In addition to disability and physical function, interests include health and health behaviour around retirement, cognitive function and psychological well-being in older people, and the later life health trajectories of those who have healthy behaviours and low risk profiles (compared with those who do not). The group research in these areas uses data from the English Longitudinal Study of Ageing and from its sister study, the US Health and Retirement Study (HRS).