Mechanisms of Ageing
Our population is growing older, and challenging us to find ways to ensure that our old age can be healthy and productive.
Ageing is the biggest single risk factor for disease. Therefore, research on the basic biology of ageing is vital in order to understand age-related diseases and conditions such as Alzheimer’s, cardiovascular disease and immune frailty.
Age-related factors predisposing to any one disease are often common to other diseases. Thus it is vital that research on the basic biology of ageing is carried out in a multidisciplinary environment. This enables the synergistic approach necessary to tackle our challenges.
What is King's doing?
Here at King's, we are pursuing a broad range of research interests on the mechanisms of ageing. These range from sub-cellular biochemistry and signaling studies, through studies using model organisms such as Drosophila and C. elegans, to whole body neurological and physiological studies in man.
Staff from the Schools of Biomedical Sciences, Medicine, Social Science & Public Policy and the Institute of Psychiatry bring their expertise, facilities and resources to tackle our challenges.
Professor Clive Ballard, Wolfson Centre for Age-Related Diseases
Dr QueeLim Ch'ng, MRC Centre for Developmental Neurobiology
Professor Ballard’s main research is related to neurodegenerative and cerebrovascular disease in older people. He has led clinical trials in Alzheimer’s disease, Parkinson’s disease dementia and Down’s syndrome dementia; and clinico-pathological studies related to synuclein diseases, cerebrovascular pathology and the pathological hallmarks of Alzheimer’s disease. His interests are expanding to include the evolution of pathological substrates with ageing, the key mechanisms underpinning these changes and the identification of robust biomarkers. Read more about Professor Clive Ballard.
Dr Jonathan Corcoran, Wolfson Centre for Age-Related Disease
Dr Ch-ng is interested in how neuroendocrine circuits affect ageing in response to environmental cues in C. elegans. He dissects food- and temperature-related transcriptional responses in the nervous system to understand how they encode and integrate multiple environmental cues. He is also examining how the expression and secretion of insulin-like peptides that modulate ageing are affected by environmental factors. Read more about Dr Ch'ng.
Professor Pat Doherty, Wolfson Centre for Age-Related Diseases
Dr Corcoran is interested in the role of nuclear receptor signaling in the maintenance and regeneration of the nervous system with a particular focus on the role of the retinoid signaling pathway in neurodegenerative diseases. Read more about Dr Corcoran.
Dr Deborah Dunn-Walters, Dept of Immunobiology
Professor Doherty has recently published on a dramatic age-dependent reduction in neurogenesis in the adult sub-ventricular zone. This can be restored by treatment with a variety of dugs that activate the CB2 cannabinoid receptor. Current studies aim to determine the underlying cause of the decline in neurogenesis, as well as optimise drug treatment paradigms to prevent it. Read more about Professor Doherty.
Dr Britta Eickholt, MRC Centre for Developmental Neurobiology
Dr Dunn-Walters’ research examines the impact of ageing on the humoral immune system. Her work is focused on how ageing affects the quality of the B cell response, how the B cell repertoire changes with age and how this affects vaccine responses to both T-dependent and T-independent antigens. Read more about Dr Dunn-Walters.
Professor Paul Francis, Wolfson Centre for Age-Related Diseases
Dendritic spines receive most of the excitatory synaptic input in the brain. Dendritic spines are dynamic and continuously change shape, resulting from actin binding proteins that regulate the actin cytoskeleton. Interference of the actin cytoskeleton inhibits spine motility and impairs synaptic plasticity, suggesting that spine shape and function are intricately linked. By investigating the signaling properties that regulate actin binding proteins and the dynamic properties of dendritic spines, Dr Eickholt is hoping to build a better understanding into the mechanisms that may underlie the development of cognitive impairments in the aged. Read more about Dr Eickholt.
Dr David Andrew Green, Dept of Physiology
Professor Francis’ research interests are the biochemical correlates of cognitive and behavioural symptoms in people with dementia, and animal and cellular models of dementia for discovery of new treatments and biomarkers. Read more about Professor Francis.
Dr Wendy Hall, Division of Nutritional Sciences
Dr Green’s research reflects an interest in multi-system physiology spanning movement, balance, sensory and cardiorespiratory control. He is particularly interested in how the changes one associates with ageing (but may also reflect disuse) influence how systems react, interact and adapt to the challenges that 21st century living pose. Read more about Dr Green.
Dr Chris Hammond, Dept of Twin Research & Genetic Epidemiology
Dr Hall's primary interest is the role of diet in vascular ageing. One of her objectives is to determine the effects that non-nutrient biologically-active compounds, such as flavonoids (specifically soy isoflavones), have on arterial health. Her work has been focused on vascular ageing occurring after the menopause; these studies typically involve acute and chronic dietary intervention studies. Another strand of research relates to the intracellular mechanisms that mediate the vascular endothelial response to different dietary fatty acids. Read more about Dr Hall.
Professor Stephen Harridge, Division of Applied Biomedical Research
Dr Hammond is exploring common eye diseases of ageing, including cataract, glaucoma and age-related macular degeneration, working with a cohort of elderly twins to understand the genetic epidemiology of these diseases. Biomarkers of ageing, such as telomere length, nuclear cataract, serum markers as well as extensive cardiovascular, bone, muscle and dietary phenotypes are combined with genome-wide linkage and association analyses to examine both genetic, environmental and gene-environment interactions. He is collecting and analysing cross-sectional and longitudinal data. Read more about Dr Hammond.
Dr Susan John, Dept of Immunobiology
Professor Harridge has two main interests in ageing research. The first relates to the adaptability of skeletal muscle mass and function in later life. He is interested in the role of local growth factors (particularly IGF-I and its splice variants) in relation to hypertrophy in the muscles of older people. More recently, he has developed a human primary muscle cell culture model to study satellite cell (obtained from older people) proliferation and differentiation, key factors in muscle repair and remodeling.
His second interest is the study of the biology of human ageing, using master athletes as a model. The biology of ageing (i.e. the rate at which a system declines over time) can best be studied in these individuals since they are free from the confounding effects of disuse- and inactivity- associated pathologies. Read more about Professor Harridge.
Dr Lindsay McDermott, Division of Pharmaceutical Science
Dr John studies signaling and gene expression in the immune system. She is developing work to elucidate the changes in signaling that contribute to age-related immune frailty. Read more about Dr John.
Professor Giovanni Mann, Cardiovascular Science Division
Dr McDermott's research seeks to determine differences in fatty acid and retinoid binding protein gene expression in placenta tissue from normal pregnancies and those complicated by intrauterine growth retardation. She is also examining fatty acid and retinoid binding protein function in the BeWo cell line. Read more about Dr McDermott.
Professor Ivor Mason, MRC Centre for Developmental Neurobiology
Professor Mann is interested in elucidating the molecular mechanisms conferring vascular protection in ageing, and hypothesises that upregulation of the redox sensitive transcription factor NF-E2-related factor 2 (Nrf2) increases the expression phase II detoxifying and longevity-related enzymes. Since activation of Nrf2/antioxidant response element pathway confers increased tolerance to oxidative stress, it seems likely that Nrf2 signaling plays a key role in the regulation of longevity. Read more about Professor Mann.
Dr Lawrence Moon, Wolfson Centre for Age-Related Diseases
Professor Mason is using the zebrafish as a model system in which to study the regulation of neural stem cells in the adult brain. The fish brain continues to grow throughout life and neurogenesis is supported by multiple stem cell niches. His goal is to determine how local signaling interactions regulate renewal versus differentiation of stem cells. Lessons learned from this accessible and malleable system will be applied to mammalian adult neural stem cells. Read more about Professor Mason.
Dr Jane Preston, Division of Nutritional Sciences
Stroke is an age-related disease which disables many people. Dr Moon's long-term research goal is to identify and test novel strategies for promoting recovery after CNS injuries including stroke. Gene profiling studies and gene therapy approaches are used to identify novel potential therapies. He also uses aged rat models of stroke to test novel therapeutic strategies in vivo. Read more about Dr Moon.
Professor Tim Spector, Division of Genetics & Molecular Medicine
Dr Preston is interested in late-life ageing of cerebrospinal fluid (CSF) dynamics, CSF secretion and fluid turnover rate. This is combined with proteomic analysis of CSF to identify biomarkers for ageing which may increase risk of late life neurodegeneration or serve as indices of CNS 'biological' age. Blood-CSF and blood-brain barriers transport capability with age (e.g. of thyroid hormone, IGF-2, amyloid peptides) and permeability of the barriers, with emphasis on in vivo methods. Read more about Dr Preston.
Dr Stephen Sturzenbaum, Division of Pharmaceutical Science
Professor Spector’s Twin Research and Genetic Epidemiology Ageing Programme aims to explore genetic influences and markers of the ageing process in humans. They have substantial research resources including a large cohort of adult twins who have been followed longitudinally for up to ten years, with reporting on muscle mass, bone loss, cardiovascular changes, cognitive changes, cataract and refractive error changes and vitamin D levels. Other resources include telomere measures on 3000 twins and longitudinal DNA collections. A tissue bank of twins with genome-wide expression data on fat, skin, lymphoblasts and muscle will be available in 2009. Read more about Professor Spector.
Dr Leonie Taams, Dept of Immunobiology
Polyphenols are a group of secondary plant dyes shown to have a positive effect on health and aging across the animal kingdom. Flavonoids have recently been shown to significantly extend the life span of the nematode C. elegans, a notion that is currently being investigated at the molecular level (whole genome microarrays, qPCR and RNAi) via a BBSRC funded fellowship awarded to the Sturzenbaum lab. Read more about Dr Sturzenbaum.
Dr Peter Zammit, Randall Division of Cell & Molecular Biophysics
Dr Taams’ main research interest is the regulation of the immune response in humans during health and disease. Alterations in the induction or efficacy of regulatory cell subsets during ageing could affect the body's ability to clear infection, control autoimmune responses or prevent tumour growth. By investigating T cell and monocyte/macrophage function in diseases that are associated with the ageing population, such as rheumatoid arthritis and ovarian cancer, she hopes to understand better how immunoregulatory mechanisms help to maintain health. Read more about Dr Taams.
Adult skeletal muscle is a post-mitotic tissue and so hypertrophy, maintenance and repair is carried out by resident stem cells termed satellite cells. While the satellite cell population efficiently maintains muscle mass and function in healthy adults, with advancing age, there is a gradual loss of muscle mass (sarcopenia), which eventually compromises function. Dr Zammit is interested in understanding how both intrinsic changes in satellite cells, and the changing muscle environment, each contribute to this age-related loss of muscle. Read more about Dr Zammit.