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EATING BEHAVIOUR IN PHYSIOLOGICAL AND EATING BEHAVIOUR IN PHYSIOLOGICAL AND PATHOLOGICAL AGINGPATHOLOGICAL AGING
E. FerrariE. 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
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FOODFOOD
sensorysensoryaspectaspect
source ofsource offeelsfeels
signalssignals
pleasurepleasure
IDENTIFICATIONIDENTIFICATION
HEDONICSHEDONICS
NUTRITIONNUTRITION
(Blundell - Münich 1995)(Blundell - Münich 1995)
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Biological Biological regulationregulation
Eating Eating behaviourbehaviour
NutritionNutrition
PhysiologyPhysiologyMetabolismMetabolism
BrainBrain
Enviromental Enviromental adaptationadaptation
(BLUNDELL J.E. et HILL A.- PV 1992)(BLUNDELL J.E. et HILL A.- PV 1992)
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Internal signals Environmental changes
Metabolic(glucose-lipids
amino acids)
Hormonals(insulinGastrointestinal hormones)
Neurogens(gastric distension)
ThermostaticEating behaviour
Hungry - satiety
FACTORS INVOLVED IN THE REGULATION OF FACTORS INVOLVED IN THE REGULATION OF EATING BEHAVIOUREATING BEHAVIOUR
Food palatability
Adversive behaviours about food
Psychological cortical factors
HYPOTHALAMUSHYPOTHALAMUS
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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
EATING BEHAVIOUREATING BEHAVIOUR
SHORT TERM MECHANISMS(hungry/satiety feeling)• Gastrointestinal pathway (neuronal/hormonal messages)• Pancreatic hormones• Nutrients
AREAS INVOLVED
GERONT.GERIATR., PAVIA
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HYPOTHALAMUSHYPOTHALAMUS
LATERAL AREALATERAL AREA(Dopamine)(Dopamine)
VENTROMEDIAL AREAVENTROMEDIAL AREA(Serotonin)(Serotonin)
HUNGERHUNGER SATIETYSATIETY
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MAIN FACTORS INVOLVED IN THE REGULATION OF MAIN FACTORS INVOLVED IN THE REGULATION OF FOOD INTAKEFOOD INTAKE
INHIBITORSINHIBITORS
SerotoninSerotonin
LeptinLeptin
Insulin (central)Insulin (central)
CRFCRF
Cholecystokinine (CCK)Cholecystokinine (CCK)
BombesinBombesin
CatecholaminesCatecholamines
STIMULATORSSTIMULATORS
GlucocorticoidsGlucocorticoids
OpioidsOpioids
GABAGABA
GalaninGalanin
NoradrenalinNoradrenalin
PYYPYY
PPPP SomatostatinSomatostatin
Neuropeptide Y (NPY)Neuropeptide Y (NPY)
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AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN THE CONTROL OF EATING BEHAVIOUR AND THEIR THE CONTROL OF EATING BEHAVIOUR AND THEIR
CONSEQUENCESCONSEQUENCES
AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN THE CONTROL OF EATING BEHAVIOUR AND THEIR THE CONTROL OF EATING BEHAVIOUR AND THEIR
CONSEQUENCESCONSEQUENCES
OpioidsOpioids
CCKCCK
Nitric oxideNitric oxide
Cytokines (TNFCytokines (TNF))
AmilynAmilyn
Taste and smellTaste and smell
GH / IGF-1GH / IGF-1
TestosteroneTestosterone
EstrogensEstrogens
Reduction of caloric uptake (particularly fats)Reduction of caloric uptake (particularly fats)
Early satiety sensationEarly satiety sensation
Early satiety sensationEarly satiety sensation
Increased protein catabolism, lipolysisIncreased protein catabolism, lipolysis
Reduction of protein anabolism (insulin antagonism)Reduction of protein anabolism (insulin antagonism)
Reduction of caloric uptakeReduction of caloric uptake
Reduction of caloric uptake, lowering of protein anabolismReduction of caloric uptake, lowering of protein anabolism
Reduction of caloric uptake, lowering of protein anabolismReduction of caloric uptake, lowering of protein anabolism
Reduction of caloric uptakeReduction of caloric uptake
FactorsFactors AgeAge ConsequencesConsequences
GERONT.GERIATR., PAVIAGERONT.GERIATR., PAVIA
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30 40 50 60 70 80 9030 40 50 60 70 80 90
-60-60
-40-40
-20-20
00
2020
4040
6060
30 40 50 60 70 80 90 30 40 50 60 70 80 90
% fat% fat
BMIBMI
musclemuscle massmass
MenMen
Muller et al, 1994Muller et al, 1994
WomenWomen% fat% fat
BMIBMI
Age(years)Age(years)
% d
iffer
ence
% d
iffer
ence
Effect of aging on BMI, body fat and muscle mass Effect of aging on BMI, body fat and muscle mass in men and womenin men and women
(BLSA, cross sectional analysis)(BLSA, cross sectional analysis)
musclemuscle massmass
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GERONT.GERIATR., PV,GERONT.GERIATR., PV,
CALORIC REQUIREMENT AND ENERGY CALORIC REQUIREMENT AND ENERGY EXPENDITURE ACCORDING TO AGEEXPENDITURE ACCORDING TO AGE
Reduction of metabolic basal rate:Reduction of metabolic basal rate:
Reduction of energy expenditure during Reduction of energy expenditure during physical activity :physical activity :
Daily caloric requirement :Daily caloric requirement :30 y = 2700 Kcal30 y = 2700 Kcal80 y = 2100 Kcal80 y = 2100 Kcal
- 1.66 Kcal / m / h /10 y- 1.66 Kcal / m / h /10 y22
- 200 Kcal/die from 45 to 75 y- 200 Kcal/die from 45 to 75 y
- 500 Kcal/die after 75 y- 500 Kcal/die after 75 y
(Baltimore Longitudinal Study)(Baltimore Longitudinal Study)
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FOODFOODINTAKEINTAKE
ENERGYENERGYEXPENDITUREEXPENDITURE
WEIGHT LOSS:WEIGHT LOSS:FOOD INTAKEFOOD INTAKE
FOOD INTAKEFOOD INTAKE
FOOD INTAKEFOOD INTAKE
ENERGY EXPENDITUREENERGY EXPENDITURE
ENERGY EXPENDITUREENERGY EXPENDITURE
ENERGY EXPENDITUREENERGY EXPENDITURE
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from Jeanrenaud, PD 1997from Jeanrenaud, PD 1997
HYPOTHALAMUSHYPOTHALAMUS
PERIPHERYPERIPHERY
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• 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
LEPTIN
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Hypothalamic NPY
LEPTIN FAT MASS
INTERACTION LEPTIN - NPY
food intake
BAT activity
insulin secretion
-
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Long-term regulation: LEPTIN
LEPTIN
Decrease of food intake
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
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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
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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
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Cholecystokinine (CCK)
In the CNS, CCK is released from hypothalamic
neurons during feeding
ICV administration (very low doses) inhibits food
intake (CCKA)
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Leptin/CCK synergy
might promote weight
loss through:
resting
metabolic rate
thermogenesys
efficiency of
absorption and
storage of nutrients
Matson CA et al, 2000
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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)
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GHRELIN
Intraperitoneal injection
Central injection
Wren MA et al, 2001
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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
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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
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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
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Long-term regulation: INSULIN
Food intake+
Insulin
CNS
NPY, melanocortin system
FOOD INTAKE
Sympathetic
activity
THERMOGENESYS
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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
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MCH = melanin concentrating MCH = melanin concentrating hormone hormone
NPY = neuropeptide YNPY = neuropeptide Y
CRF = corticotropin-releasing CRF = corticotropin-releasing factorfactor
AGRP = agoute-related peptideAGRP = agoute-related peptide
CART = cocaine-amphetamine-CART = cocaine-amphetamine- regulated transcript regulated transcript
CCK = cholecystokininCCK = cholecystokinin
GLP-1= glucagon-like GLP-1= glucagon-like peptide-1peptide-1
GRP= gastric-related peptideGRP= gastric-related peptide
PYY = peptide YYPYY = peptide YY
TNF = tumor necrosis factorTNF = tumor necrosis factor
IL = interleukinIL = interleukin
NO = nitric oxideNO = nitric oxide
From MORLEY J.E., J Geront Med Sci, 58A, 2, 131-137, 2003
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BMI acceptable valuesBMI acceptable values(National Academy Press, Washington, DC, 1989, pp 21-22)(National Academy Press, Washington, DC, 1989, pp 21-22)
45 - 54 y45 - 54 y45 - 54 y45 - 54 y 21 – 26 Kg/m21 – 26 Kg/m2221 – 26 Kg/m21 – 26 Kg/m22
More than 65 yMore than 65 yMore than 65 yMore than 65 y 24 – 29 Kg/m24 – 29 Kg/m2224 – 29 Kg/m24 – 29 Kg/m22
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ANOREXIA:
“LOSS OF THE DESIRE TO EAT”
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ANOREXIA OF ELDERLY SUBJECTSANOREXIA OF ELDERLY SUBJECTS
SINE CAUSASINE CAUSA1.1.
DEPRESSIONDEPRESSION2.2.
ATYPICAL ANOREXIA NERVOSAATYPICAL ANOREXIA NERVOSA4.4.
SENILE AND PRESENILE DEMENTIA SENILE AND PRESENILE DEMENTIA OF ALZHEIMER’S TYPEOF ALZHEIMER’S TYPE
3.3.
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GERONT. GERIATR., PAVIA
““PHYSIOLOGICAL ANOREXIA” OF AGINGPHYSIOLOGICAL ANOREXIA” OF AGING““PHYSIOLOGICAL ANOREXIA” OF AGINGPHYSIOLOGICAL ANOREXIA” OF AGING
Basal Metabolic RateBasal Metabolic Rate
Physical ActivityPhysical Activity
Feeding drive (NE, NPY, dynorphin)Feeding drive (NE, NPY, dynorphin)
CCKCCK
NONO
(From MORLEY - Am. J. Clin. Nutr. 66: 760: 1997)(From MORLEY - Am. J. Clin. Nutr. 66: 760: 1997)
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GH, DHEA, T, EGH, DHEA, T, E Free RadicalsFree Radicals CytokinesCytokines ActivityActivity
Chronic DiseaseChronic Disease Acute illnessAcute illness CytokinesCytokines ActivityActivity
AgeingAgeing
SarcopeniaSarcopenia FrailtyFrailtyProposed interrelationships between weight loss (Wt Loss), sarcopenia, Proposed interrelationships between weight loss (Wt Loss), sarcopenia, failure to thrive (FTT), and frailty. GH, growth hormone; DHEA, failure to thrive (FTT), and frailty. GH, growth hormone; DHEA, dehydroepiandrosterone sulfate; T, testosterone; E, estrogen.dehydroepiandrosterone sulfate; T, testosterone; E, estrogen.
? Wt Loss? Wt Loss
Wt LossWt Loss
FTTFTT
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““STANDARDIZATION OF NOMENCLATURE OF STANDARDIZATION OF NOMENCLATURE OF BODY COMPOSITION IN WEIGHT LOSS”BODY COMPOSITION IN WEIGHT LOSS”
CACHEXIA:CACHEXIA: involuntary loss of BCM (Body Cell involuntary loss of BCM (Body Cell
Mass) of fat-free mass, with little or no weight lossMass) of fat-free mass, with little or no weight loss
WASTING:WASTING: involuntary weight loss with loss of both involuntary weight loss with loss of both
lean and the fat masslean and the fat mass
SARCOPENIA:SARCOPENIA: involuntary loss of muscle mass involuntary loss of muscle mass
(Roubenoff R. et al, Amer. J. Clin. Nutr. 661: 192-6; 1997)(Roubenoff R. et al, Amer. J. Clin. Nutr. 661: 192-6; 1997)
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PRINCIPAL CAUSES OF WEIGHT LOSS IN PRINCIPAL CAUSES OF WEIGHT LOSS IN AGING (according MORLEY)AGING (according MORLEY)
1)1) SocialSocial
2)2) PsychologicalPsychological
3)3) MedicalMedical
4)4) Age-related Age-related
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SOCIAL CAUSES OF WEIGHT LOSS IN SOCIAL CAUSES OF WEIGHT LOSS IN ELDERLY SUBJECTSELDERLY SUBJECTS
PovertyPoverty
Social segregationSocial segregation
Shopping and cooking problemsShopping and cooking problems
In institutionalized subjects:In institutionalized subjects:
- different dietary habit- different dietary habit
- monotony of meals- monotony of meals
- problems in eating together with demented patients - problems in eating together with demented patients
or subjects with handicapsor subjects with handicaps
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PSYCHOLOGICAL CAUSES OF WEIGHT PSYCHOLOGICAL CAUSES OF WEIGHT LOSS IN ELDERLY SUBJECTSLOSS IN ELDERLY SUBJECTS
BereavementsBereavements
Loneliness or feeling of abandonmentLoneliness or feeling of abandonment
Rejection for a too sad life and wish for deathRejection for a too sad life and wish for death
DepressionDepression
DementiaDementia
Tardive anorexia nervosaTardive anorexia nervosa
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DRUG INFLUENCES ON NUTRITIONDRUG INFLUENCES ON NUTRITION
MODIFICATION OF MODIFICATION OF APPETITEAPPETITE
REDUCTION OF REDUCTION OF INTESTINAL INTESTINAL ABSORPTIONABSORPTION
ALTERATIONS OF ALTERATIONS OF METABOLISMMETABOLISM
CHANGES IN CHANGES IN NUTRIENTS NUTRIENTS EXCRETIONEXCRETION
Isoniazid e Penicillamine (increased vit. BIsoniazid e Penicillamine (increased vit. B12 12
excretion)excretion)Colestiramine Colestiramine → loss of liposoluble vitamins→ loss of liposoluble vitamins
Sympathomimetics increase the caloric Sympathomimetics increase the caloric requirementrequirement
Antibiotics, barbiturates, cytostatics, Antibiotics, barbiturates, cytostatics, non non steroidal antininflammatoryssteroidal antininflammatorys, colchicine, , colchicine, corticosteroids, laxativescorticosteroids, laxatives
REDUCTION: REDUCTION: Antibiotics, Penicillamine, non Antibiotics, Penicillamine, non steroidal antininflammatorys, laxatives, steroidal antininflammatorys, laxatives, levodopa, fenformine, cardiokineticslevodopa, fenformine, cardiokinetics
INCREASE: gastrokinetic hormones, INCREASE: gastrokinetic hormones, sulphonylureas, neeurolepticssulphonylureas, neeuroleptics
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THE MEALS-ON-WHEELS APPROACH TO WEIGHT LOSSTHE MEALS-ON-WHEELS APPROACH TO WEIGHT LOSS
M M E E AALLSS
OONN
WWHHEEEELLSS
==========
====
============
MMedicationedication EEmotional (depression, late life mania)motional (depression, late life mania)AAnorexia Nervosa (tardive); Alcoholismnorexia Nervosa (tardive); AlcoholismLLate life paranoiaate life paranoiaSSwallowing disorderswallowing disorders
OOral factors (dental problema; xerostomia)ral factors (dental problema; xerostomia)NNo Money (poverty)o Money (poverty)
WWandering and other dementia related behaviorsandering and other dementia related behaviorsHHyperthyroidism; hyperparathyroidismyperthyroidism; hyperparathyroidismEEntry problems (malabsorbtion)ntry problems (malabsorbtion)EEating problemsating problemsLLow salt; low cholesterol dietow salt; low cholesterol dietSShopping problemshopping problems
(J.F. MORLEY et al. PV 1992)(J.F. MORLEY et al. PV 1992)
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MALNUTRITION IN THE ELDERLYMALNUTRITION IN THE ELDERLY
5-10% of elderly people living at home5-10% of elderly people living at home
25-60% of elderly people living in a 25-60% of elderly people living in a nursing homenursing home
50% of hospitalized elderly subjects50% of hospitalized elderly subjects
••
••
••
GERONT.GERIATR., PV, 1995
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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
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PROTEIN-ENERGY MALNUTRITION IN OLDER PERSONS
From Morley, Am J Clin Nutr, 1997:66:760
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
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