Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

NUTRITION,PHYSICAL STATUS,BODY COMPOSITION, SARCOPENIAPART 2

Erika Pétervári and Miklós SzékelyMolecular and Clinical Basics of Gerontology – Lecture 4

Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of DebrecenIdentification number: TÁMOP-4.1.2-08/1/A-2009-0011

TÁMOP-4.1.2-08/1/A-2009-0011

What is the consequence of• body weight gain in middle-

aged individuals?• the anorexia/cachexia in old

populations?

Consequences

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Changes in body compositionwith ageThe water content of the body changes proportionately with FFM•Water content of the FFM is stable.• Ratio of intracellular / extracellular volume is unknown.

Bone minerals change proportionately with FFM• By 65 it decreases by 10 – 15 %.• In females the rate of decrease is enhanced after menopause. This dramatic fall can be prevented by estrogen supplementation.• In active athletes the rate of decrease is similar, but the peak bone mass is higher. • 4 months chronic bedrest – 1.4% deficit, not regained even after 6 months.

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Muscle mass and strength diminishes slowly until 50, then the rate is enhanced – SARCOPENIA • Between 30 and 80 there is a 30-40 % decrease (also in athletes).• Especially the quick, dynamic contractions are impaired.- The number of motoneurons/motor units fall.- The production of muscle proteins decreases (especially that of type II fibers)

•Muscle hypertrophy may be elicited by intensive training even in the elderly (12 weeks – 3 times a week – +10%)

Changes in body compositionwith age

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Fat, fat-free mass and cell mass ofmales and females at various ages

Fat , fat-free mass, and cell mass of males () and females () at various ages, values are given, and the number of subjects in each age group is noted.

27 58 3337

42

18

89 33 44 72 54 13

18–25 25–35 35–45 45–55 55–65 65–85Age (years)

Abso

lute

wei

ght (

kg)

10

20

30

40

50

60

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Partial/incomplete starvation

Composition of loss in BMI & MR • Adipose tissue 95%• Liver 50%• Skeletal muscles 30%• Bones 8%• Brain 3%• BMR 30%Starvation (aging anorexia) protein

breakdown

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Decay of Nature, or Senile Marasmus, has the greatest number of deaths attributed to it. Their ages vary from 69 to 92 years. The inmates affected with this gradual wasting of body, which approaches very slowly, have usually their mental faculties clear and unclouded till the last, but complain of loss of appetite, bowels costive, pulse small, quick and weak, and sleepless nights, feel no pain, and look on death with seeming indifference and carelessness, in many cases as a happy release. With regards to treatment, medicines are of little use.(H. S. Purdon, 1868)

Decay of Nature

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Anorexia (leads to sarcopenia)• frailty• functional disorders• cognitive disorders• decubitus (bed-sore, pressure ulcer)• hip fractures• quality of life • mortality

TÁMOP-4.1.2-08/1/A-2009-0011Pathogenesis and functional vs. metabolic consequences of sarcopenia

SARCOPENIADecreasedfood intake

Impaired ADLS

MalnutritionCytokines

Increasedoxidative stress

Low testosterone,estrogen, GH, IGF-1

Decreasedphysical activity

GH = growth hormone; IGF-1 = insulin-like growth factor-1;BMR = basal metabolic rate;ADLS = activities of daily living

Decreasedwalking speed

Impairedbalance Osteoporosis Falls

DecreasedBMR

Impairedthermoregulation

Decreasedphysical activity

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Energydeficit

Energyexcess

The spectrum of caloric intake from insufficient to excessive calories

Hypothetical U-shaped curve over the spectrum of caloric intake from insufficient to excessive calories, emphasizing negative physiologic effects at both extremes and positive or hormetic effects within a range of normal (regulated) caloric intake.

Longevity Cancer Autoimmune disease Oxidative stressPositive

effects

Negativeeffects

Longevity Cancer Autoimmune disease Oxidative stress

Parenchymal cell numberLoss of functionStarvationDeath

Regulated diet↑

Calories

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Main mechanisms which lead to•weight gain of middle-aged groups•anorexia of the old

Mechanisms

TÁMOP-4.1.2-08/1/A-2009-0011Dysorexia in the elderly: insufficient adaptation to overfeeding

Regulatory disorder!

Phase 2Overfeeding

Body

Wei

ght C

hang

e Du

ring

and

Afte

r Ove

rfeed

ing

(kg)

–1

Phase 3Ad Libitum

Study DayLowest Weight

0

1

2

3

20 29 41 77

Younger Men Older Men

*

*140

1

130

120

110

100

90

80

70

60

Time After Overfeeding (d)2 3 4 5 6 7 8 9 10

Ener

gy In

take

(% o

f W

eigh

t-Mai

nten

ance

Val

ue)

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–3Highest Weight

0

–1

1

2

20 29 41 77

–2

Dysorexia in the elderly: insufficient adaptation to underfeeding

Regulatory disorder!

Phase 2Underfeedin

g

Body

Wei

ght C

hang

e Du

ring

and

Afte

r Und

erfe

edin

g (k

g)

Phase 3Ad Libitum

Study Day

Younger Men Older Men

Ener

gy In

take

(% o

f W

eigh

t-Mai

nten

ance

Val

ue) 140

1

130

120

110

100

90

80

70

60

Time After Underfeeding (d)2 3 4 5 6 7 8 9 10

** *

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Components of energy balance

FI MR HL

Tc Feedingstate

Nutritional stateBody weight

FI = food intakeMR = metabolic rateHL = heat lossTc = core temperature

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Metabolic rate (MR)

BMR, RMR, energy expenditure decrease with age (especially in men).Possible causes: • FI ( specific dynamic activity of

nutrients, thermic effect of food, diet-induced thermogenesis as well)

• T3-level• sensitivity to norepinephrine• muscle mass and muscle strength• activity of Na-K-ATP-ase

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Food intake (FI): frequent causes of undernutrition in the elderly Social factors• poverty• problems with independent shopping, cooking etc. • social isolation (lack of partners, table setting )Psychological factors• deprivation, sorrow, anxiety, mourning• dementia• depressionPhysical factors• immobilization• need for assistance at feeding (e.g. difficulties in slicing the food)• problems of dental health and oral hygiene• problems of dental prosthesis

TÁMOP-4.1.2-08/1/A-2009-0011Frequent causes of undernutrition in the elderly: pathological conditions• Effort to eat (e.g. COPD, congestive heart failure)• Food intake associated pain (e.g. abdominal ischemia)• Recurrent infections, tumors (e.g. TNF)• Ectopic hormon production (e.g. bombesin)• GI disorders (e.g. meteorism, malabsorption,

circulatory disorders)• Endogenous toxicosis (e.g. uremia)• Endocrine disorders (e.g. Sheehan syndrome,

Addison’s disease)• Medication (e.g. digoxin, theophyllin) or its withdrawal• Neuropsychiatric disorders (e.g. stroke, aging anorexia

nervosa)

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Real age-related anorexia“aging anorexia”1 Decreased requirement• low MR • low activity

2 Decreased hedonic value• taste • smell• vision

3 Depressed “feeding drive” • neurotransmitters (e.g. opioids, amines, peptides) • nutritional factors (eg. Zn, nutrients, metabolites)

4 Enhanced satiety factors• cholecystokinin (CCK)

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While BMR fell by less than 20%, kcal intake fell by about 35% between 20 and 70 years.Chronic disease MR rapid progression.

Basal metabolic rate (BMR) and mean daily caloric intake by age groups

Age (years) BMR (W/m2) mean daily kcal intake (kcal/day)

2 64

10 55

20 48 2,482

30 45 2,372

40 44 2,146

50 43 1,967

60 42 1,822

70 40 1,624

80 1,484

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Regulation of FI and MR

Short-term regulation1 Nutrients2 Metabolites3 Gastrointestinal hormones4 Neural signalsLong-term regulation1 Insulin2 Leptin

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Hypothalamic regulation of FI

NPY/AgRPneuron

Orexigenicpathway

POMCneuron

Ghrelin

Leptin Anorexigenicpathway

Activates NPYrelease

AgRPrelease

Inhibits

Arcuate nucleus

Activates

MSHrelease

MC4receptors

Inhibititon of melanocortin

pathways

Paraventicular nucleus

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Age-related changesin the regulationIn the middle-aged• orexia, body weight (FM) increases• CCK effects , leptin/insulin effect ,

NPY, POMC

In the old• anorexia, relative starvation, protein-calorie-

malnutrition, muscle mass• CCK-effects , leptin/insulin effects ,

NPY , POMC effect

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Age-related changesin the regulation• The central hypothalamic regulation of food

intake and metabolic rate depends on the dynamic balance between anabolic and catabolic mediator systems. • Age-related changes in the central regulation

may contribute to the development of obesity in middle-aged and sarcopenia/cachexia of aging.