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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.

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slide1

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

slide2

signals

IDENTIFICATION

sensoryaspect

pleasure

HEDONICS

FOOD

source offeels

NUTRITION

(Blundell - Münich 1995)

slide3

Biological regulation

Brain

Eating behaviour

Physiology

Metabolism

Nutrition

Enviromental adaptation

(BLUNDELL J.E. et HILL A.- PV 1992)

slide4

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

slide5

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

slide6

HYPOTHALAMUS

LATERAL AREA(Dopamine)

VENTROMEDIAL AREA(Serotonin)

SATIETY

HUNGER

slide7

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

slide8

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

slide9

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

slide11

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,

slide12

FOODINTAKE

ENERGYEXPENDITURE

WEIGHT LOSS:

FOOD INTAKE

ENERGY EXPENDITURE

FOOD INTAKE

ENERGY EXPENDITURE

FOOD INTAKE

ENERGY EXPENDITURE

slide13

HYPOTHALAMUS

PERIPHERY

from Jeanrenaud, PD 1997

leptin
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
slide15

INTERACTION LEPTIN - NPY

food intakeBAT activityinsulin secretion

Hypothalamic NPY

-

LEPTIN

FAT MASS

slide16

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

slide17

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

slide18

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
slide19

Cholecystokinine (CCK)

  • In the CNS, CCK is released from hypothalamic neurons during feeding
  • ICV administration (very low doses) inhibits food intake (CCKA)
slide20

Leptin/CCK synergy might promote weight loss through:

  •  resting metabolic rate
  •  thermogenesys
  •  efficiency of absorption and storage of nutrients

Matson CA et al, 2000

slide21

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)
slide22

Wren MA et al, 2001

GHRELIN

Intraperitoneal injection

Central injection

slide23

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
slide24

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

slide25

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

slide26

THERMOGENESYS

 FOOD INTAKE

CNS

NPY, melanocortin system

  • Sympathetic

activity

Long-term regulation: INSULIN

+

Food intake

Insulin

slide27

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
slide28

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

slide29

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

slide31

ANOREXIA:

“LOSS OF THE DESIRE TO EAT”

slide32

ANOREXIA OF ELDERLY SUBJECTS

1.

SINE CAUSA

2.

DEPRESSION

3.

SENILE AND PRESENILE DEMENTIA OF ALZHEIMER’S TYPE

4.

ATYPICAL ANOREXIA NERVOSA

slide33

“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

slide34

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.

slide35

“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)

slide36

PRINCIPAL CAUSES OF WEIGHT LOSS IN AGING (according MORLEY)

  • Social
  • Psychological
  • Medical
  • Age-related
slide37

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

slide38

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
slide39

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

the meals on wheels approach to weight loss
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)

slide41

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

slide42

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

slide43

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