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 1

Erika Pétervári and Miklós SzékelyMolecular and Clinical Basics of Gerontology – Lecture 3

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

Body composition – energy storesIn a healthy young human being:• Adipose tissue: circa 15 kg (130–140,000

kcal)• Protein: around 10-12 kg (35–40,000 kcal)• Carbohydrates: circa 0.3 kg (1,100 kcal)• Water: around 42 kg• Minerals: about 4 kg

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LBM FM20-y 60 + 13 = 73 kg70-y 48 + 26 = 74 kgExcess weight (if any) = mainly fat

(NOT only in fat tissue)Age-related obesity:

fat accumulation in parenchymal cells (muscle, liver) LIPOTOXICITY

Lean body mass (LBM) andfat mass (FM)

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All the world's a stage,And all the men and women merely players;They have their exits and their entrances;And one man in his time plays many parts,His acts being seven ages. At first the infant,Mewling and puking in the nurse's arms;Then the whining school-boy, with his satchelAnd shining morning face, creeping like snailUnwittingly to school. And then the lover,Sighing like furnace, with a woeful balladMade to his mistress' eyebrow. Then a soldier,Full of strange oaths, and bearded like a pard,Jealous in honour, sudden and quick in quarrel,Seeking the bubble reputation.Even in the cannon's mouth. And then the justice,In fair round belly with good capon lin'd,With eyes severe and beard of formal cut,Full of wise saws and modern instances;And so he plays his part. The sixth age shiftsInto the lean and slipper'd pantaloon,With spectacles on nose and pouch on side;His youthful hose, well sav'd, a world too wideFor his shrunk shank; and his big manly voice,Turning again childish treble, pipesAnd whistles in his sound. Last scene of all,That ends this strange eventful history,Is second childishness and mere oblivion;Sansteeth, sanseyes, sanstaste, Sanseverything.

Shakespeare: As you like it

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Body composition – energy stores

Body Fat Ranges for Standard Adults 1

1 Based on NIH/WHO BMI Guidelines.

Underfat Healthy Overfat Obese

Underfat Healthy Overfat Obese

0% 10% 20% 30% 40%

Female 20-39Age 40-59

60-79

Male 20-39Age 40-59

60-79

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Changes in body compositionwith ageBody weight increases until 60-65, then it starts to decrease 18-55 years 55-65 years 65-80 years 8-9 kg/decade1-2 kg/decade-1,-2 kg/decadeThe body weight of active athletes does not increase.The fat content of the body increases with age

25 years 75 years 16 – 25 % 28 – 41 % males – females12 – 15 kg 22 – 25 kg

In active athletes the increase is blunted (~young, lean, sedentary). Intensive training decreases abdominal fat. Males have a tendency for visceral fat accumulation, after menopause females too.Fat free mass (FFM) is stable until 40, then it decreases

25 years 75 years 62 – 46 kg - 3.5 kg decrease/decade, (-3 – -4 %/decade)

FFM values and changes are relatively stable with small individual differences. The rate of decrease is similar in athletes.

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Does aging make fat go MAD?(During aging certain cell types degenerate and lipids accumulate in non-adipose tissues.)

Adipogenesis and aging

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Impaired adipogenesis and fat tissue function with aging

cytokines,cellular stress

C/EBP PPAR

LIP CHOP

fatty acid

handling, glucose

metabolism

Fundamental aging processes

(reactive oxygen species, telomeres, other)

Differentiation-Dependent Genes

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Fat distribution with aging

Mesenchymaladipocyte-like

default(MAD)cells

Fat in fatdepotsFat outside fat depotsInsulinsensitivityCytokines(TNFα, IL-6)

Preadipocytes

Osteoblasts

Muscle satellite cells

Macrophages

Other mesenchymal cells AGING

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Peroxisome proliferator-activating receptor (PPAR )

FABPfatty acid binding protein

UCPuncoupling protein

LXRliver-X-receptor-

ABCA1ATP-binding cassette A1

PDK4pyruvat-dehydrogenase kinase, isoenzyme 4

PEPCKphosphoenolpyruvat-carboxykinase

PPAR

insulin sensitizationglucose lowering

triglyceride loweringantiatheroscleroticantihypertensive

Adipose FA storage (FABP)

FA oxidation (UCP3)

Macrophage oxLDL uptake(CD36) CH efflux (LXR and

ABCA1)

Muscle glucose oxidation

(PDK4) FA oxidation (UCP3)

Liver gluconeogenesis

(PEPCK)

FFA

FFA

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Fat metabolism

LEPTINcAMP

activated prot.kinase

ac CoA carboxylase inhibition

FA OXIDATION

FA transferto mitoch.

carnitinpalmitoyl

acyltransfera

seactivation

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Fat massMale Female

18-y 18% 33%85-y 36% 44%

Muscle mass20-40% loss SARCOPENIA

Fat, muscle and aging

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Body weight andadiposity index in rats

Body

Wei

ght o

r Adi

posit

y In

dex

Age (mo)3 12 18 24 30

100

200

300

400

500

600

Adiposity IndexBody Weight

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“Optimal” 4.5 kg rise (<6%) (30-y period)

Reality White male 9.7 kgmean BMI ~30 or

>30Black male 10.1 kg

(n = 16,000)White female12.0 kg

Black female20.8 kg

“Optimal” and real rise of body weight in a 30-y period

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Body Mass Index

Body Weight (kg)

Height (m)2

= 20-25

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AGE at start BW-change

MALE FEMALE

25–45-y + 3.4% + 5.2%

45–65-y no ch. no ch.

65–75-y - 4.1% - 6.3%

Bodyweight change (course of 9y)

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BMI associated with lowest mortality(nadir of curve)

Age group BMI20-29 21.430-39 21.640-49 22.950-59 25.860-69 26.6

U-shaped relationship betweenBMI and mortality ratio

Men

’s m

orta

lity

ratio

(× 1

00)

50

>210190

170150130110

9070

Body Mass Index (kg/m2)151821242730333639

151821242730333639

39

>210190

170150130110

9070501518212427303336

TÁMOP-4.1.2-08/1/A-2009-0011The effect of age on the BMI associated with the lowest mortality

The regression lines were computed separately for men and for women.Note that there is a strong effect of age on the BMI associated with the lowest mortality and that the regression lines for men and women are nearly identical.

26

24

22

20

18 30 40 50 60Age (yrs)

Body

Mas

s Ind

ex (w

t/ht2 )

20 70

28

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BMI associated with the lowest mortality

Age (years) Male Female

20-29 21.4 19.5

30-39 21.6 23.4

40-49 22.9 23.2

50-59 25.8 25.2

60-69 26.6 27.3

Increased proportion of fat (♂ 36%, ♀ 44%)Height ! Normal values may be different (calculations?)