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EATING BEHAVIOUR IN PHYSIOLOGICAL AND PATHOLOGICAL AGING

EATING BEHAVIOUR IN PHYSIOLOGICAL AND PATHOLOGICAL AGING. E. Ferrari. Dept of Internal Medicine and Medical Therapy, Chair of Gerontology and Geriatrics – University of Pavia, Italy. Morgan Hall, Room 114– University of California, Berkeley Thursday May 5, 2005. signals. IDENTIFICATION.

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EATING BEHAVIOUR IN PHYSIOLOGICAL AND PATHOLOGICAL AGING

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  1. EATING BEHAVIOUR IN PHYSIOLOGICAL AND PATHOLOGICAL AGING E. Ferrari Dept of Internal Medicine and Medical Therapy, Chair of Gerontology and Geriatrics – University of Pavia, Italy Morgan Hall, Room 114– University of California, Berkeley Thursday May 5, 2005

  2. signals IDENTIFICATION sensoryaspect pleasure HEDONICS FOOD source offeels NUTRITION (Blundell - Münich 1995)

  3. Biological regulation Brain Eating behaviour Physiology Metabolism Nutrition Enviromental adaptation (BLUNDELL J.E. et HILL A.- PV 1992)

  4. FACTORS INVOLVED IN THE REGULATION OF EATING BEHAVIOUR Internal signals Environmental changes Food palatability Adversive behaviours about food Metabolic (glucose-lipids amino acids) Hormonals (insulin Gastrointestinal hormones) HYPOTHALAMUS Psychological cortical factors Neurogens (gastric distension) Eating behaviour Hungry - satiety Thermostatic

  5. EATING BEHAVIOUR AREAS INVOLVED • MAINTENANCE OF BODY WEIGHT • Long term signals • Fat mass • nutrients • hormones • taste • memory • environmental factors • food research • food choice • food intake • thermogenesys • Other metabolic factors • SHORT TERM MECHANISMS • (hungry/satiety feeling) • Gastrointestinal pathway • (neuronal/hormonal messages) • Pancreatic hormones • Nutrients GERONT.GERIATR., PAVIA

  6. HYPOTHALAMUS LATERAL AREA(Dopamine) VENTROMEDIAL AREA(Serotonin) SATIETY HUNGER

  7. STIMULATORS Glucocorticoids Opioids GABA Galanin Noradrenalin PYY PP MAIN FACTORS INVOLVED IN THE REGULATION OF FOOD INTAKE INHIBITORS Neuropeptide Y (NPY) Serotonin Leptin Insulin (central) CRF Cholecystokinine (CCK) Bombesin Catecholamines Somatostatin

  8. AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN THE CONTROL OF EATING BEHAVIOUR AND THEIR CONSEQUENCES Factors Age Consequences Opioids CCK Nitric oxide Cytokines (TNFa) Amilyn Taste and smell GH / IGF-1 Testosterone Estrogens Reduction of caloric uptake (particularly fats) Early satiety sensation Early satiety sensation Increased protein catabolism, lipolysis Reduction of protein anabolism (insulin antagonism) Reduction of caloric uptake Reduction of caloric uptake, lowering of protein anabolism Reduction of caloric uptake, lowering of protein anabolism Reduction of caloric uptake GERONT.GERIATR., PAVIA

  9. Effect of aging on BMI, body fat and muscle mass in men and women (BLSA, cross sectional analysis) 60 Men Women % fat 40 % fat 20 BMI BMI % difference 0 -20 muscle muscle mass -40 mass -60 30 40 50 60 70 80 90 30 40 50 60 70 80 90 Age(years) Muller et al, 1994

  10. 2 - 1.66 Kcal / m / h /10 y CALORIC REQUIREMENT AND ENERGY EXPENDITURE ACCORDING TO AGE (Baltimore Longitudinal Study) Daily caloric requirement :  30 y = 2700 Kcal 80 y = 2100 Kcal  Reduction of metabolic basal rate: Reduction of energy expenditure during physical activity :  - 200 Kcal/die from 45 to 75 y - 500 Kcal/die after 75 y GERONT.GERIATR., PV,

  11. FOODINTAKE ENERGYEXPENDITURE WEIGHT LOSS: FOOD INTAKE ENERGY EXPENDITURE FOOD INTAKE ENERGY EXPENDITURE FOOD INTAKE ENERGY EXPENDITURE

  12. HYPOTHALAMUS PERIPHERY from Jeanrenaud, PD 1997

  13. LEPTIN • Polypeptide hormone secreted by fat cells • Blood levels proportional to total fat mass • Plasma circadian rhythm: acrophase during the night (4 am), nadir during the afternoon • Pulsatility in opposite phase with ACTH and cortisol • Effects: - appetite inhibition - effects on GH-RH and GnRH

  14. INTERACTION LEPTIN - NPY food intakeBAT activityinsulin secretion Hypothalamic NPY - LEPTIN FAT MASS

  15. Long-term regulation: LEPTIN Decrease of food intake Increase of energy expenditure (sympathetic activation) WEIGHT LOSS LEPTIN The biological impact of leptin is probably more pronounced when leptin levels are decreasing. Increased sensation of hunger correlated with reduction of plasma levels during moderate energy restriction

  16. Short-term regulation: LEPTIN • Stomach is a source of leptin • Food or CCK administration induces leptin secretion • Enhanced effect of gastrointestinal satiety factors in the presence of leptin Bado A, et al, Nature, 1998; Cinti S et al, Int J Obes, 2000

  17. Cholecystokinine (CCK) • Endocrine cells of the proximal small intestine • Stimulated by dietary fats, amino acids and small peptides • Inhibition of food intake by activation of CCKA receptors (vagal afferent signals) • Decrease of meal size • Inhibition of gastric emptying

  18. Cholecystokinine (CCK) • In the CNS, CCK is released from hypothalamic neurons during feeding • ICV administration (very low doses) inhibits food intake (CCKA)

  19. Leptin/CCK synergy might promote weight loss through: •  resting metabolic rate •  thermogenesys •  efficiency of absorption and storage of nutrients Matson CA et al, 2000

  20. GHRELIN • Produced by stomach and hypothalamus •  during fasting and  by the presence of nutrients in the stomach • Central administration increases hypothalamic expression of NPY • Potential role in long-term body weight regulation (increase of adiposity sustained over 1 week of treatment)

  21. Wren MA et al, 2001 GHRELIN Intraperitoneal injection Central injection

  22. GHRELIN : orexigenic effects • Increase of food intake independently from GH and GHRH release • The increased expression of hypothalamic NPY mRNA is abolished by co-injection of Y1 receptor antagonist • The satiety effect of leptin is abolished by co-injection of ghrelin  leptin / ghrelin antagonism (NPY/Y1 pathway) • Orexigenic effect mediated partly by increases of AgRP production, leading to the inhibition of hypothalamic melanocortin system

  23. CYTOKINES IL-6, TNF-α = physiological regulators ? They may influence insulin sensitivity or leptin production GLUCOCORTICOIDS CATABOLIC in periphery ANABOLIC in the CNS Interaction with insulin and leptin in long-term regulation of food intake and adiposity

  24. Parasimpathetic nerves Incoming nutrients (glucose and aminoacids) Incretin hormones (GLP-1 and GIP) Long-term regulation: INSULIN + Food intake Insulin Insulin concentration proportional to body fat content and recent carbohydrate and protein intake

  25. THERMOGENESYS  FOOD INTAKE CNS NPY, melanocortin system • Sympathetic activity Long-term regulation: INSULIN + Food intake Insulin

  26. Long-term regulation: INSULIN • Peripheral anabolic effects (Increased lipid synthesis and storage) • Insulin response to glucose = smaller degree of subsequent weight gain • Post feeding insulin preferentially transported into the hypothalamus • Chronic consumption of high fat diet impairs brain insulin transport

  27. MCH = melanin concentrating hormone NPY = neuropeptide Y CRF = corticotropin-releasing factor AGRP = agoute-related peptide CART = cocaine-amphetamine- regulated transcript CCK = cholecystokinin GLP-1= glucagon-like peptide-1 GRP= gastric-related peptide PYY = peptide YY TNF = tumor necrosis factor IL = interleukin NO = nitric oxide From MORLEY J.E., J Geront Med Sci, 58A, 2, 131-137, 2003

  28. BMI acceptable values (National Academy Press, Washington, DC, 1989, pp 21-22) 45 - 54 y 21 – 26 Kg/m2 More than 65 y 24 – 29 Kg/m2

  29. ANOREXIA: “LOSS OF THE DESIRE TO EAT”

  30. ANOREXIA OF ELDERLY SUBJECTS 1. SINE CAUSA 2. DEPRESSION 3. SENILE AND PRESENILE DEMENTIA OF ALZHEIMER’S TYPE 4. ATYPICAL ANOREXIA NERVOSA

  31. “PHYSIOLOGICAL ANOREXIA” OF AGING Basal Metabolic Rate Physical Activity Feeding drive (NE, NPY, dynorphin) CCK NO (From MORLEY - Am. J. Clin. Nutr. 66: 760: 1997) GERONT. GERIATR., PAVIA

  32. GH, DHEA, T, E • Free Radicals • Cytokines  Activity  Chronic Disease • Acute illness •  Cytokines  Activity Ageing Wt Loss ? Wt Loss FTT Sarcopenia Frailty Proposed interrelationships between weight loss (Wt Loss), sarcopenia, failure to thrive (FTT), and frailty. GH, growth hormone; DHEA, dehydroepiandrosterone sulfate; T, testosterone; E, estrogen.

  33. “STANDARDIZATION OF NOMENCLATURE OF BODY COMPOSITION IN WEIGHT LOSS” WASTING: involuntary weight loss with loss of both lean and the fat mass CACHEXIA: involuntary loss of BCM (Body Cell Mass) of fat-free mass, with little or no weight loss SARCOPENIA: involuntary loss of muscle mass (Roubenoff R. et al, Amer. J. Clin. Nutr. 661: 192-6; 1997)

  34. PRINCIPAL CAUSES OF WEIGHT LOSS IN AGING (according MORLEY) • Social • Psychological • Medical • Age-related

  35. SOCIAL CAUSES OF WEIGHT LOSS IN ELDERLY SUBJECTS Poverty Social segregation Shopping and cooking problems In institutionalized subjects: - different dietary habit - monotony of meals - problems in eating together with demented patients or subjects with handicaps

  36. PSYCHOLOGICAL CAUSES OF WEIGHT LOSS IN ELDERLY SUBJECTS • Bereavements • Loneliness or feeling of abandonment • Rejection for a too sad life and wish for death • Depression • Dementia • Tardive anorexia nervosa

  37. DRUG INFLUENCES ON NUTRITION REDUCTION: Antibiotics, Penicillamine, non steroidal antininflammatorys, laxatives, levodopa, fenformine, cardiokinetics MODIFICATION OF APPETITE INCREASE: gastrokinetic hormones, sulphonylureas, neeuroleptics Antibiotics, barbiturates, cytostatics, non steroidal antininflammatorys, colchicine, corticosteroids, laxatives REDUCTION OF INTESTINAL ABSORPTION Sympathomimetics increase the caloric requirement ALTERATIONS OF METABOLISM Isoniazid e Penicillamine (increased vit. B12 excretion) Colestiramine → loss of liposoluble vitamins CHANGES IN NUTRIENTS EXCRETION

  38. THE MEALS-ON-WHEELS APPROACH TO WEIGHT LOSS M E A L S O N W H E E L S = = = = = = = = = = === Medication Emotional (depression, late life mania) Anorexia Nervosa (tardive); Alcoholism Late life paranoia Swallowing disorders Oral factors (dental problema; xerostomia) No Money (poverty) Wandering and other dementia related behaviors Hyperthyroidism; hyperparathyroidism Entry problems (malabsorbtion) Eating problems Low salt; low cholesterol diet Shopping problems (J.F. MORLEY et al. PV 1992)

  39. MALNUTRITION IN THE ELDERLY • 5-10% of elderly people living at home • 25-60% of elderly people living in a nursing home • 50% of hospitalized elderly subjects GERONT.GERIATR., PV, 1995

  40. PROTEIN-ENERGY MALNUTRITION IN OLDER PERSONS S: sadness C: cholesterol < 4.14 mmol/l A: albumin < 4 g/dl L: loss of weight E: eating problems S: shopping problems or inhability to prepare meals From Morley, Am J Clin Nutr, 1997:66:760

  41. PROTEIN-ENERGY MALNUTRITION IN OLDER PERSONS • Conditions associated with protein-energy • Immunodeficiency (decreased helper T cells; increased infection • Pressure ulcers • Anemia • Osteopenia and sarcopenia • Falls • Cognitive deficits • Altered drug metabolism • Euthyroid sick syndrome • Decreased maximal breathing capacity • Decreased wound healing From Morley, Am J Clin Nutr, 1997:66:760

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