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.
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 Faculties of Life Sciences & Medicine, Social Science & Public Policy and the Institute of Psychiatry, Psychology & Neuroscience bring their expertise, facilities and resources to tackle our challenges.
Dr Wendy Hall, Division of Diabetes & Nutritional Sciences
Professor Chris Hammond, Dept of Twin Research
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.
& Genetic Epidemiology
Professor Stephen Harridge, Centre of Human & Aerospace
Professor 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 Professor Hammond.
Professor Giovanni Mann, Cardiovascular Division
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.
Professor Manuel Mayr, Cardiovascular Division
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 Julien Ochala, Centre of Human & Aerospace Physiological
Pofessor Mayr's research interests are in proteomics and metabolomics combined with genetic manipulation. By combining proteomics and metabolomics in animal models of cardiovascular research, they try to bridge the gap between molecular and systems biology.
Other research intrests inlcude stem cell differentiation into vascular Cells. Stem cell research holds great promise for regenerative medicine and tissue engineering. Our current studies focus to decipher the distinguishing proteomic and metabolic features of stem cell-derived cardiovascular cells. The overall aim is to identify key proteins or small molecules, that may be drug targets for promoting stem cell differentiation or novel paracrine factors leading to arterio- and angiogenesis. Read more here,
Professor Lucilla Poston, Division of Women's Health
Dr Julien Ochala’s research focuses on understanding the cellular and molecular mechanisms underlying muscle wasting in various conditions, including ageing and premature ageing syndromes. To achieve this he uses techniques that range from single molecule biophysics, muscle cell physiology, X-ray diffraction and high-resolution confocal microscopy. His overarching goal is to provide sufficient knowledge to identify drug targets and design novel therapeutic interventions. Read more here.
Professor Catherine Shanahan, Cardiovascular Division
Professor Poston leads the Division of Women's Health within the School of Medicine at King’s College London, and is Director of the Maternal and Fetal Research Unit based at the St.Thomas’ Campus. The division encompasses a multidisciplinary team of clinicians, scientists and health professionals with a focus on translational research.
Research interests include Developmental Origins of Health and Disease,
and Pre-eclampsia. Read more here,
Dr Tanya Shaw, Centre for Inflammation Biology and Cancer
Professor Catherine Shanahan is interested in the molecular regulation of vascular smooth muscle cell (VSMC) phenotype and how it relates to vascular dysfunction in diseases such as atherosclerosis, diabetes, hypertension, chronic renal failure and ageing. Read more about Professor Catherine Shanahan.
Dr Richard Siow, Cardiovascular Division
Dr Shaw is team leader in the Centre for Molecular and Cellular Biology of Inflammation. Research in the Shaw lab focuses on the cellular and molecular mechanisms of wound healing in the skin and the ovaries. She is particularly interested in how tissue repair processes may go wrong – potentially resulting in pathological scars such as keloids on the skin and contributing to the development of cancer in the ovary. Read more about Dr Shaw here.
Professor Tim Spector, Department of Twin Research & Genetic Epidemiology
Dr Richard Siow's research interests are Antioxidants, oxidative stress and growth factors in cardiovascular health and disease, cardiovascular nutrigenomics. Read more about Dr Richard Siow.
Professor Stephen Sturzenbaum, Institute of Pharmceutical 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.
Professor Leonie Taams, Centre for Inflammation Biology and Cancer Immunology (CIBCI)
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 Professor Sturzenbaum.
Professor Fiona Watt, Centre for Stem Cells & Regenerative Medicine
Professor 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 Professor Taams.
Professor Antony Young, Division of Genetics & Molecular Medicine
Professor Watt's major research interest is in the role of stem cells in adult tissue maintenance. For many of her studies she uses mammalian epidermis as a model system, both in the context of genetically modified mice and epidermal reconstitution in culture.
Current projects are exploring self-renewal and lineage selection by human and mouse epidermal stem cells, the role of stem cells in epidermal and oral tumour formation, and the nature of mesenchymal cells in skin. Professor Watt has active collaborations with bioengineers and chemists in order to study stem cell-niche interactions in vitro.
Read more about Professor Fiona Watt.
Professor Peter Zammit, Randall Division of Cell
Antony Young is a Professor of Experimental Photobiology and heads up the Photobiology Unit at King's. Antony is interested in the acute and long-term adverse effects of solar ultraviolet radiation (UVR) on the skin, the most important of which is skin cancer. The Photobiology Unit is also interested in vitamin D photosynthesis which is the only established beneficial effect of solar UVR.
Read more about Antony Young.
& Molecular Biophysics
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. Professor 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 Professor Zammit.