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Knowledge and Quality of Life with Particular Reference to the Ageing Population

Knowledge and Quality of Life with Particular Reference to the Ageing Population. George K Radda University Laboratory of Physiology and Cardiac Science University of Oxford UK. Life Expectancy.

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Knowledge and Quality of Life with Particular Reference to the Ageing Population

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  1. Knowledge and Quality of Life with Particular Reference to the Ageing Population George K Radda University Laboratory of Physiology and Cardiac Science University of Oxford UK

  2. Life Expectancy • The 20th centurysaw a dramatic increase in life expectancy from 47y in 1900 to around 80y today • Most of this gain can be attributed to improved social conditions and success in preventing and treating major infectious diseases (eg TB) • Further gains will depend on delivering new healthcare advances

  3. 20 20-39 19 60 and 18 over 17 Population (millions) 16 15 14 13 12 11 10 2000 2020 2030 The Global Age Shift • By 2030 the UK will have 19m people over 60 who will out number younger adults by one fifth FORESIGHT REPORT MAY 2000

  4. Improve Quality of Life in Ageing • Challenges • to promote healthy ageing • to improve the management of • age-related illnesses • to encourage leading edge, multidisciplinary • research that will inform these aims

  5. Genes, Brain and Ageing - Mouse to Man • What are the key genes in ageing? • How do they relate to ageing effects • on brain and cognitive function? • Can we use the information from • functional genomics to delay or • reverse the effects of ageing? Babraham Institute - Laboratory of Cognitive & Developmental Neuroscience

  6. Major Health Challenges • Ageing • Mental health • Infectious diseases • Obesity/Nutrition • Heart disease • Cancer

  7. Mental Health Annual age and gender specific incidence rates of dementia per 100 person years of risk • Dementia • 200 new cases/day in UK; • 1.5 million anticipated by 2030 • No drug slows the disease • Prevention desirable • Alzheimer’s • 5% of cases genetically determined • 95% not truly familial • Many modifiable risk factors are shared with vascular heart disease and stroke 18 16 14 12 Women Men 10 Incidence rate 8 6 4 2 0 75-79 80-84 85-89 90-94 65-69 70-74 95+ Age Group

  8. Multidisciplinary Research andNeurodegenerative Disease • Mental ill health and neurodegenerative • diseases cost the UK economy £6.3bn each year • Costs will increase still further as the population ages • Current treatments contain symptoms, but do • not effect cure

  9. e.g. bipolar disorder Individual cognitive behavioural therapy couple e.g. schizophrenia antipsychotics Brain Families e.g. depression therapy public L - Dopa, e.g. Parkinson’s Cell Population e.g. risk be haviour health stem cells gene therapy parenting Genome Environment e.g. antisocial behaviour e.g. Huntington’s Understanding and Treating Brain Disease

  10. Magnetic Resonance Imaging • Safe and non-invasive • Detects changes in normal, diseased or injured patients • Can identify those at risk of disease before symptoms develop

  11. M Rossor & N Fox, Institute of Neurology

  12. M Rossor & N Fox, Institute of Neurology

  13. M Rossor & N Fox, Institute of Neurology

  14. M Rossor & N Fox, Institute of Neurology

  15. M Rossor & N Fox, Institute of Neurology

  16. M Rossor & N Fox, Institute of Neurology

  17. M Rossor & N Fox, Institute of Neurology

  18. M Rossor & N Fox, Institute of Neurology

  19. M Rossor & N Fox, Institute of Neurology

  20. M Rossor & N Fox, Institute of Neurology

  21. M Rossor & N Fox, Institute of Neurology

  22. contracting expanding M Rossor & N Fox, Institute of Neurology

  23. 200 µm Pathophysiology of Parkinson’s Disease cortex Selective degeneration of a subpopulation of dopaminergic (DA) midbrain neurons DA neurons are essential for voluntary movement control. Dopaminergic midbrain neurons in mouse brain slice (tyrosine hydroxylase immunostain). Birgit Liss & Jochen Roeper, MRC Anatomical Neuropharmacology Unit Selective survival of a subset of dopaminergic neurons in a mouse model of Parkinson’s disease. Define molecules governing the activity of living DA neurons (brain-slice patch-clamp techniques).

  24. Functional Genomics with Single-cell Resolution Genes responsible for selective survival of individual dopaminergic neurons provide novel therapeutic targets for Parkinson‘s disease A: cytoplasm harvesting via patch-pipette (living neurons) B: laser-based microdissection (fixed neurons) 1. Isolation of mRNA from individual vulnerable and resistant DA neurons single cell or PCR-tube PCR-tube laser 2. Linear mRNA amplification, synthesis of labelled cDNA cDNA Hybridisation with DNA array DA neuron 1 DA neuron 2 3. DNA-array based comparison of single-cell gene expression profiles Birgit Liss & Jochen Roeper, MRC Anatomical Neuropharmacology Unit, Oxford

  25. Treating Parkinson’s Disease The MRC and Parkinson’s Disease Society have recently funded a £1.25m trial to test the long-term effectiveness of surgery versus drug treatment for Parkinson’s Disease • Parkinson’s Disease is controlled by • drugs but these become less effective • over time and the period of relief they • offer also decreases • Surgery provides longer periods of • quality living as opposed to the 1-2h • that drugs offer, but the long term • effects on quality of life of the patient • and carer need to be evaluated • The trial is being led from the QE • hospital in Birmingham

  26. Embryonic Stem Cells • UK NICHE • Pioneering UK research by Martin Evans • TheUK recently became the first country in the world to approve properly conducted research on the use of embryonic stem cells • This provides a window of opportunity and indeed an obligation to grasp the potential of stem cell based therapies

  27. Stem Cells Feeders + LIF R Lovell-Badge NIMR Blastocyst ES cells Suspension - LIF +/-RA, +FGF/ -FGF +/-G418 selection for Sox2bgeo Embryoid bodies ES cell derived neurons Derivation and in vitro differentiation of Embryonic Stem (ES) cells

  28. STEM CELLS: SHAPING THE FUTURE Stakeholders MRC BBSRC CCLRC EPSRC ESRC Government Departments & Ministers Donors Patients Clinicians Scientists Government Research Councils AS BHF CRUK DUK JDRF PDS WT • DRIVERS • Serious diseases • UK legislation • Scientific advances • Opportunity Charities STEM CELLS Industry Large pharma and SME’s Consumers and Focus Groups Regulatory Agencies HFEA MHRA DH International Agencies Forum of 13

  29. STEM CELLS: SHAPING THE FUTURE Funders Co-ordinating Committee • 15 Agencies • Communications Coalition • Annual Conference • Career Development Fellowships • Training Course • Research Funding (JDRF/MRC MoU) • Res. Councils: BBSRC, CCLRC, EPSRC, ESRC, MRC • Res. Charities: AS, BHF, CRUK, DUK, JDRF, PDS,WT • Reg. Agencies: DH, HFEA, MHRA

  30. STEM CELLS: SHAPING THE FUTURE • National Facilities • UK Stem Cell Bank • - established at NIBSC with funding from MRC & BBSRC • - local management committee established • - one year devoted to recruitment/refurbishment • - clinical grade facilities installed; MHRA accreditationrequired • - research grade facilities completed • - ready to accession research grade lines • - applications to bank research grade lines currently under • review by Steering Committee

  31. STEM CELLS: SHAPING THE FUTURE Codes of Practice Draft Code of Practice for the Use of Human Stem Cell Lines Draft Code of Practice for the UK Stem Cell Bank Shortly to be on the MRC web site for consultation Currently on the MRC web site for consultation www.mrc.ac.uk

  32. STEM CELLS: SHAPING THE FUTURE • Communications • UK Funders Communications Coalition • - briefing pack on stem cells • - MORI poll of public attitudes • Corporate Communication Activities • - UK and EU parliamentary briefings • - MRC attitudinal survey of IVF and other donors • Consumers - Consumer Liaison Groups review guidance documents - Steering Committee includes two lay members

  33. STEM CELLS: SHAPING THE FUTURE Europe • European Commission - FP6: €17.5b total - €2.2b for genomics & biotechnology for health - stem cell research a priority • European Parliament - EUTissues and Cells Directive (April 2004) - provides a regulatory framework • United Nations - cloning debate

  34. STEM CELLS: SHAPING THE FUTURE International Stem Cell Forum • 13 agencies from 12 countries - meets twice per year - portfolio sharing - policy discussions - joint funding initiatives - collaborative agreement AUSTRALIA, CANADA, FINLAND, FRANCE, GERMANY, ISRAEL, JDRF, JAPAN, SINGAPORE, SWEDEN, THE NETHERLANDS, UK, USA

  35. STEM CELLS: SHAPING THE FUTURE International Stem Cell Forum • Joint Initiatives - characterisation of stem cell lines (UK lead) - ethics landscape (Canada lead) - IPR Landscape (Australia lead) - web database of international research and training opportunities (UK lead)

  36. Dementia & Quality of Life How to extend the active participation of older people with dementia in society • Investigate cognition of the external environment by people with dementia • Identify design factors which influence the ability of older people with dementia to negotiate their external environment • Offer guidance to designers on the criteria to consider in developing urban areas that are accessible to those with dementia • Find ways to promote communication for elderly people with dementia using multimedia techniques

  37. Gloucester Smart House

  38. Gloucester Smart House Locator– A device to help people locate lost items e.g. purse, glasses Bath monitor – A monitor to help stop people filling the bath to overflowing whilst still allowing full control of the taps Cooker monitor – A device that monitors the cooker and acts to prevent dangerous situation occurring Night-time guidance – Guides the resident of a house to the toilet with gentle lighting Communications– Research into reliable and accurate means of communication with people with dementia

  39. Major Health Challenges • Ageing • Mental health • Infectious diseases • Obesity/Diabetes • Heart disease • Cancer

  40. Obesity Rates: Current and Projected Children England 50 Adults 40 Population percentage with BMI > 30kg/m2 30 20 10 0 2010 2000 1990 1980 1970 1960

  41. 30 25 20 Diagnosed cases 15 People (millions) 10 5 Projected diagnosed cases 0 1960 1970 1980 1990 2010 2020 2030 2040 2050 2000 Prevalence of Diagnosed Diabetes in the United States Diagnosed (1960-1998) and Projected Diagnosed (2000-2050) Cases Year Data for 1960-1998 from the National Health Interview Survey, NCHS, CDC. Projected data for 2000-2050 from Boyle JP, et al, Diabetes Care 24:1936-40, 2001.

  42. Heart Disease 600 Courtesy of Stefan Neubahrer 500 400 300 Cumulative number of vascular deaths Placebo and tablets 200 Aspirin Streptokinase Streptokinase plus 100 aspirin 0 0 7 14 21 28 35 Days

  43. Heart Protection Study Clinical Trials Service Unit,Oxford (R Collins) Supported by MRC, BHF & Merck & Roche Vitamins • After allowance for non-compliance, 40mg daily simvastatin safely reduces the risk of heart attack, of stroke, and of revascularisation by at least one-third • 5 years of statin treatment typically prevents these “major vascular events” in about: • 100 of every 1000 with previous MI • 80 " " other CHD • 70 " " diabetes (age 40+) • 70 " " previous stroke • 70 " " other PVD irrespective of cholesterol level (or age, or sex, or other treatments)

  44. Genetic Diversity • The current world population of 6 billion descends from a few tens of thousands of progenitors who inhabited Africa some 200,000 years ago • Small, isolated populations (eg in remote parts of Sardinia) interbreed and maintain only a limited degree of genetic variation • In contrast, large populations (eg in the UK) show much greater variation • This offers 2 routes into studying genetic diversity and mapping common diseases like heart disease and dementia

  45. The UK Biobank Medical Research Council Wellcome Trust Department of Health

  46. BioBankUK • Long term prospective research framework • Relative contributions of genotype, environmental exposure and chance to risk of common diseases • Cohort of 500,000 adults (aged 45 – 69) • Nested case control studies • Monitoring for incident disease • Central repository of biological samples and linked database • Genotype • Other biological assays • Exposure data

  47. The Continuum of Biological Research Prevention Individual Animal Families Understanding Health and Disease Organ Populations Cell Genome Environment Treatment Diagnosis

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