The Untold Consequences of Ageing: what goes wrong and what can we do about it?

1. Denbigh School Science Lecture 11th November 2010 The Untold Consequences of Ageing: what goes wrongand what can we do about it? Dr John S. Young Faculty of Health & Medical Sciences University of Surrey

2. 40 Over 50y 30 Over 65y % 20 10 0 2010 2020 2030 • “An ageing population” Life expectancy: • ~30y (1910) • 79y (2010) Office for National Statistics

3. Why is the UK’s population ageing? Improved: • Food supply / nutrition • Health • Hygiene

4. Improved Nutrition, Health and Hygiene: recent examples? Clockwise, from top-left: • Jamie Oliver’s ‘School Dinners’ campaign; • Labelling of nutritional content of food; • Ban on smoking in public places - pubs, restaurants, train stations • Alcohol rubs in hospitals • Ban on sun-bed use for under-18s

5. DNA Environmental insults Free radicals Mutations and epimutations RNA Altered RNA Protein Altered proteins Normal structure and function Anti-oxidants Degradation • Science: underpinning increased life expectancy? UV radiation cigarette smoke O2- OH- Polyphenols: resveratrol, flavonoids Vitamins A,C,E Enzymes Bilirubin Uric acid Implicated in: Cancers, stroke, diabetes, atherosclerosis, etc. And ageing

6. More calorie restriction; Increased life expectancy 1/3rd calorie content normal diet • Science: research to extend life even further • Free radicals and environmental insults: DNA damage • Calorific restriction: animals live longer In mice a reduced calorie diet = a longer life Great news! …Or is it? Weindruch et al. 1986. J. Nutrition

7. Problems associated with increased life expectancy? • Increased time in poor health e.g. from 1981 to 2001: 15% (women), 34% (men) * • Financial and social costs - who will pay for these? * http://news.bbc.co.uk/1/hi/health/3958495.stm

8. Physical characteristics of old age? • Reduced mobility • Weakening of bones • Change in posture • Diseases: - dementia (e.g. Alzheimer’s) - motor control disorders (e.g. Parkinson’s, Motor Neurone Disease) - blindness - type II diabetes - (cardiovascular disease) - cancers - incontinence - auto-immune diseases • Reduced taste  Many changes that reduce Quality of Life

9. Outline Parkinson’s Disease Incontinence

10. Outline Parkinson’s Disease Incontinence

11. Motor control: how the body produces movement

12. Motor control: how the body produces movement

13. Motor control: how the body produces movement

14. Parkinson’s Disease: characteristics • Tremor at rest - ‘shaking palsy’ • Rigidity - also a symptom of arthritis • Akinesia (slowness of movement) - also affects facial expressions and coordination • Postural instability (impaired balance) - small steps; sometimes appear ‘drunk’ Also: • slow / slurred speech • small, cramped writing • constipation and urinary incontinence • increased sweaty or oily skin

15. Parkinson’s Disease: characteristics Before: http://www.youtube.com/watch?v=xejclvwbwsk

16. Parkinson’s Disease: diagnosis Transverse section through the mid-brain Lewy body accumulation of alpha-synuclein protein forming inclusions called Lewy bodies Parkinson’s disease ‘Normal’ Note the absence of the black band (substantia nigra) • physical symptoms • neurological examination • response to medication (levodopa) Post-mortem:

17. Parkinson’s Disease: malfunctioning traffic lights ‘Normal’ Motor cortex Motor cortex movement movement Corpus striatum Corpus striatum Thalamus Thalamus Substantia nigra Substantia nigra Loss of substantia nigra Substantia nigra Substantia nigra: forms part of a circuit, coordinating movement Parkinson’s Disease Initially: uncoordinated Eventually: rigidity

18. Parkinson’s Disease: existing treatment • Levodopa - transformed into dopamine - counteracting loss of dopamine in substantia nigra • But: - treat symptoms, not cause - side-effects: nausea, involuntary movements, stiffness - effectiveness decreases over time • Other agents affect dopamine pathways • Low protein diet • Exercise

19. Parkinson’s Disease: existing treatment • Deep brain stimulation: implant of ‘brain pacemaker’ FINE WIRE ELECTRODE SUBSTANTIA NIGRA CONNECTIVE WIRE PACEMAKER

20. Parkinson’s Disease: existing treatment • Deep brain stimulation: implant of ‘brain pacemaker’ After: http://www.youtube.com/watch?v=IOHtUzW02cg

21. Parkinson’s Disease: treatment • Treatments of tomorrow • Levodopa ‘add-ons’ - change way in which levodopa is metabolised; increase effectiveness • Trans-cranial Magnetic Stimulation - electromagnetic coil excites or knock-outs a specific region • Genetic-linked therapies - Genetic basis of Parkinson’s; understanding more  specific therapies • Cell replacement - transplant dopamine-producing cells from adrenal medulla into brain

22. Outline Parkinson’s Disease Incontinence

23. Incontinence: lower urinary tract anatomy Kidney Kidney (cut open) Ureter ureter Bladder bladder sphincter nerves Urethra pelvic floor Female urinary tract:

24. Incontinence: storage and emptying of the bladder urine from kidneys contracted relaxed Storage relaxed contracted Emptying sensation: full bladder

25. Incontinence: different bladder diseases Urinary Tract Infection Over-active bladder Pelvic floor weakness Enlarged prostate following childbirth sporadic contractions prostate penis Antibiotics Change urine pH Various Physiotherapy Microwave radiation Normal sphincter pelvic floor Affects: Treatment:

26. Incontinence: over-active bladder Over-active bladder (OAB): • Urgency and / or urge incontinence • Increased frequency • Night-time trips to bathroom

27. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age: %

28. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life: • Night-time trips to bathroom • Co-morbidities: impaired mobility • Social impact • Depression

29. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life Large financial burden: • NHS: £500m (2% NHS budget) • Patient: £300m

30. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life Large financial burden Current treatment: Pads / bladder training • Pads: social and financial cost • Training: variable effect

31. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life Large financial burden Current treatment: Pads / bladder training • Ineffective in 50% • Side-effects inc. dementia • 70-80% drop-out Anti-muscarinics

32. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life Large financial burden Current treatment: Pads / bladder training Anti-muscarinics Botulinum toxin • General anaesthesia • Self-catheterisation • Side-effects • Cost before after (allegedly)

33. Incontinence: over-active bladder Over-active bladder (OAB) Prevalent – and increases with age Significantly impacts quality of life Large financial burden Current treatment: Pads / bladder training Anti-muscarinics Botulinum toxin • Risks: anaesthesia • Co-morbidities Open surgery

34. Incontinence: over-active bladder relaxed contracted By stimulating the sacral nerve, the outlet of the bladder is ‘closed’ and the muscle wall is relaxed Over-active bladder (OAB) - affects 1 in 3 aged 75+ - treatment: improvement in 1 of 2 people Future treatments: e.g. sacral nerve stimulation

35. Summary: • Ageing population: increased time in poor health • Parkinson’s and over-active bladder (OAB): • - don’t know cause • - drugs are partially effective, and have unpleasant side-effects • - electrical stimulation an option when drugs fail • (but any surgery is risky and expensive, so it’s not the solution for all) • More research into mechanisms • Employ new technologies to treat