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

FOODFOOD

sensorysensoryaspectaspect

source ofsource offeelsfeels

signalssignals

pleasurepleasure

IDENTIFICATIONIDENTIFICATION

HEDONICSHEDONICS

NUTRITIONNUTRITION

(Blundell - Münich 1995)(Blundell - Münich 1995)

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)

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

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

HYPOTHALAMUSHYPOTHALAMUS

LATERAL AREALATERAL AREA(Dopamine)(Dopamine)

VENTROMEDIAL AREAVENTROMEDIAL AREA(Serotonin)(Serotonin)

HUNGERHUNGER SATIETYSATIETY

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)

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

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

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)

FOODFOODINTAKEINTAKE

ENERGYENERGYEXPENDITUREEXPENDITURE

WEIGHT LOSS:WEIGHT LOSS:FOOD INTAKEFOOD INTAKE

FOOD INTAKEFOOD INTAKE

FOOD INTAKEFOOD INTAKE

ENERGY EXPENDITUREENERGY EXPENDITURE

ENERGY EXPENDITUREENERGY EXPENDITURE

ENERGY EXPENDITUREENERGY EXPENDITURE

from Jeanrenaud, PD 1997from Jeanrenaud, PD 1997

HYPOTHALAMUSHYPOTHALAMUS

PERIPHERYPERIPHERY

• 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

Hypothalamic NPY

LEPTIN FAT MASS

INTERACTION LEPTIN - NPY

food intake

BAT activity

insulin secretion

-

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

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 increases hypothalamic

expression of NPY

Potential role in long-term body weight regulation

(increase of adiposity sustained over 1 week of

treatment)

GHRELIN

Intraperitoneal injection

Central injection

Wren MA et al, 2001

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

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

Food intake+

Insulin

CNS

NPY, melanocortin system

FOOD INTAKE

Sympathetic

activity

THERMOGENESYS

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 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

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

ANOREXIA:

“LOSS OF THE DESIRE TO EAT”

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.

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)

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

““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)

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

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

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

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

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)

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

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

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