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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 sensory aspect pleasure HEDONICS source of feels NUTRITION FOOD (Blundell - Münich 1995) Biological regulation Brain Eating behaviour Physiology Metabolism Nutrition Enviromental adaptation (BLUNDELL J.E. et HILL A.- PV 1992) FACTORS INVOLVED IN THE REGULATION OF EATING BEHAVIOUR Internal signals Environmental changes Metabolic (glucose-lipids amino acids) Hormonals (insulin Gastrointestinal hormones) Food palatability HYPOTHALAMUS Neurogens (gastric distension) Eating behaviour Thermostatic Hungry - satiety Adversive behaviours about food Psychological cortical factors EATING BEHAVIOUR AREAS INVOLVED MAINTENANCE OF BODY WEIGHT • Long term signals • Fat mass • nutrients • hormones SHORT TERM MECHANISMS (hungry/satiety feeling) • Gastrointestinal pathway (neuronal/hormonal messages) • Pancreatic hormones • Nutrients • taste • memory • environmental factors • • • • • food research food choice food intake thermogenesys Other metabolic factors HYPOTHALAMUS LATERAL AREA (Dopamine) HUNGER VENTROMEDIAL AREA (Serotonin) SATIETY MAIN FACTORS INVOLVED IN THE REGULATION OF FOOD INTAKE STIMULATORS INHIBITORS Neuropeptide Y (NPY) Serotonin Glucocorticoids Leptin Opioids Insulin (central) GABA CRF Galanin Cholecystokinine (CCK) Noradrenalin Bombesin PYY Catecholamines PP Somatostatin AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN THE CONTROL OF EATING BEHAVIOUR AND THEIR CONSEQUENCES Factors Age Consequences Opioids Reduction of caloric uptake (particularly fats) CCK Early satiety sensation Nitric oxide Early satiety sensation Cytokines (TNFa) Increased protein catabolism, lipolysis Amilyn Reduction of protein anabolism (insulin antagonism) Taste and smell Reduction of caloric uptake GH / IGF-1 Reduction of caloric uptake, lowering of protein anabolism Testosterone Reduction of caloric uptake, lowering of protein anabolism Estrogens Reduction of caloric uptake GERONT.GERIATR., PAVIA Effect of aging on BMI, body fat and muscle mass in men and women (BLSA, cross sectional analysis) 60 % difference 40 Men % fat Women % fat 20 BMI BMI 0 -20 muscle mass -40 muscle mass -60 30 40 50 60 70 80 90 30 40 50 60 70 80 90 Age(years) Muller et al, 1994 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: - 1.66 Kcal / m 2 / h /10 y Reduction of energy expenditure during physical activity : - 200 Kcal/die from 45 to 75 y - 500 Kcal/die after 75 y GERONT.GERIATR., PV, FOOD INTAKE ENERGY EXPENDITURE WEIGHT LOSS: FOOD INTAKE ENERGY EXPENDITURE FOOD INTAKE ENERGY EXPENDITURE FOOD INTAKE ENERGY EXPENDITURE HYPOTHALAMUS PERIPHERY from Jeanrenaud, PD 1997 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 INTERACTION LEPTIN - NPY Hypothalamic NPY food intake BAT activity insulin secretion LEPTIN FAT MASS Long-term regulation: LEPTIN Decrease of food intake LEPTIN Increase of energy expenditure (sympathetic activation) WEIGHT LOSS 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 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 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 Cholecystokinine (CCK) In the CNS, CCK is released from hypothalamic neurons during feeding ICV administration (very low doses) inhibits food intake (CCKA) Leptin/CCK synergy might promote weight loss through: resting metabolic rate thermogenesys efficiency of absorption and storage of nutrients Matson CA et al, 2000 GHRELIN Produced by stomach and hypothalamus during fasting and by the presence of nutrients in the stomach Central administration expression of NPY increases hypothalamic Potential role in long-term body weight regulation (increase of adiposity sustained over 1 week of treatment) GHRELIN Wren MA et al, 2001 Intraperitoneal injection Central injection 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 coinjection 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 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 Long-term regulation: INSULIN Food intake + Insulin Parasimpathetic nerves Incoming nutrients (glucose and aminoacids) Incretin hormones (GLP-1 and GIP) Insulin concentration proportional to body fat content and recent carbohydrate and protein intake Long-term regulation: INSULIN THERMOGENESYS FOOD INTAKE CNS NPY, melanocortin system Sympathetic activity Food intake + Insulin 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 MCH = melanin concentrating hormone NPY = neuropeptide Y CRF = corticotropin-releasing factor AGRP = agoute-related peptide CART = cocaine-amphetamineregulated 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 BMI acceptable values (National Academy Press, Washington, DC, 1989, pp 21-22) 45 - 54 y More than 65 y 21 – 26 Kg/m2 24 – 29 Kg/m2 ANOREXIA: “LOSS OF THE DESIRE TO EAT” ANOREXIA OF ELDERLY SUBJECTS 1. SINE CAUSA 2. DEPRESSION 3. SENILE AND PRESENILE DEMENTIA OF ALZHEIMER’S TYPE 4. ATYPICAL ANOREXIA NERVOSA “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 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. “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) PRINCIPAL CAUSES OF WEIGHT LOSS IN AGING (according MORLEY) 1) Social 2) Psychological 3) Medical 4) Age-related 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 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 DRUG INFLUENCES ON NUTRITION MODIFICATION OF APPETITE REDUCTION: Antibiotics, Penicillamine, non steroidal antininflammatorys, laxatives, levodopa, fenformine, cardiokinetics INCREASE: gastrokinetic hormones, sulphonylureas, neeuroleptics REDUCTION OF INTESTINAL ABSORPTION Antibiotics, barbiturates, cytostatics, non steroidal antininflammatorys, colchicine, corticosteroids, laxatives ALTERATIONS OF METABOLISM Sympathomimetics increase the caloric requirement CHANGES IN NUTRIENTS EXCRETION Isoniazid e Penicillamine (increased vit. B12 excretion) Colestiramine → loss of liposoluble vitamins THE MEALS-ON-WHEELS APPROACH TO WEIGHT LOSS M E A L S = = = = = Medication Emotional (depression, late life mania) Anorexia Nervosa (tardive); Alcoholism Late life paranoia Swallowing disorders O = Oral factors (dental problema; xerostomia) N = No Money (poverty) W H E E L S = = = = = = 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) 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 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 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