1. Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. NUTRITION, PHYSICAL STATUS, BODY COMPOSITION, SARCOPENIA PART 1 Erika Pétervári and Miklós Székely Molecular and Clinical Basics of Gerontology – Lecture 3 Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

3. TÁMOP-4.1.2-08/1/A-2009-0011 Body composition – energy stores In 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

4. TÁMOP-4.1.2-08/1/A-2009-0011 LBMFM 20-y60+13=73 kg 70-y48+26=74 kg Excess 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) and fat mass (FM)

5. TÁMOP-4.1.2-08/1/A-2009-0011 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, seven ages His acts being seven ages. At first the infant, Mewling and puking in the nurse's arms; Then the whining school-boy, with his satchel And shining morning face, creeping like snail Unwittingly to school. And then the lover, Sighing like furnace, with a woeful ballad Made 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; sixth And so he plays his part. The sixth age shifts Into the lean and slipper'd pantaloon, With spectacles on nose and pouch on side; His youthful hose, well sav'd, a world too wide For his shrunk shank; and his big manly voice, Turning again childish treble, pipes Last scene And 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

6. TÁMOP-4.1.2-08/1/A-2009-0011 Body composition – energy stores Body Fat Ranges for Standard Adults 1 1Based on NIH/WHO BMI Guidelines. Underfat Healthy Overfat Obese Underfat Healthy Overfat Obese 0% 10% 20% 30% 40% Female 20- 39 Age 40-59 60-79 Male 20-39 Age 40-59 60-79

7. TÁMOP-4.1.2-08/1/A-2009-0011 Changes in body composition with age Body weight increases until 60-65, then it starts to decrease 18-55 years55-65 years65-80 years 8-9 kg/decade1-2 kg/decade-1,-2 kg/decade The body weight of active athletes does not increase. The fat content of the body increases with age 25 years75 years 16 – 25 %28 – 41 %males – females 12 – 15 kg22 – 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 years75 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.

8. TÁMOP-4.1.2-08/1/A-2009-0011 Does aging make fat go MAD? (During aging certain cell types degenerate and lipids accumulate in non-adipose tissues.) Adipogenesis and aging

9. TÁMOP-4.1.2-08/1/A-2009-0011 Impaired adipogenesis and fat tissue function with aging  cytokines, cellular stress  C/EBP   PPAR   LIP  CHOP  fatty acid handling, glucose metabolis m Fundamental aging processes (reactive oxygen species, telomeres, other)  Differentiation- Dependent Genes

10. TÁMOP-4.1.2-08/1/A-2009-0011 Fat distribution with aging Mesenchymal adipocyte- like default (MAD)cells  Fat in fat depots depots  Fat outside fat depots  Insulin sensitivit y  Insulin sensitivit y  Cytokines (TNFα, IL- 6)  Cytokines (TNFα, IL- 6) Preadipocyt es Osteobla sts Muscle satellite cells Macrophages Other mesenchymal cells AGING

11. TÁMOP-4.1.2-08/1/A-2009-0011 Peroxisome proliferator- activating receptor  (PPAR  ) FABP fatty acid binding protein UCP uncoupling protein LXR  liver-X-receptor-  ABCA1 ATP-binding cassette A1 PDK4 pyruvat- dehydrogenase kinase, isoenzyme 4 PEPCK phosphoenolpyruva t-carboxykinase PPAR  insulin sensitization glucose lowering triglyceride lowering antiatheroscleroticantihypertensive insulin sensitization glucose lowering triglyceride lowering antiatheroscleroticantihypertensive Adipose  FA storage (FABP)  FA oxidation (UCP3) Adipose  FA storage (FABP)  FA oxidation (UCP3) Macrophage  oxLDL uptake(CD36)  CH efflux (LXR  and ABCA1) Macrophage  oxLDL uptake(CD36)  CH efflux (LXR  and ABCA1) Muscle  glucose oxidation (PDK4)  FA oxidation (UCP3) Muscle  glucose oxidation (PDK4)  FA oxidation (UCP3) Liver  gluconeogenesis (PEPCK) Liver  gluconeogenesis (PEPCK) FFA

12. TÁMOP-4.1.2-08/1/A-2009-0011 Fat metabolismLEPTIN cAMP activated prot.kina se ac CoA carboxyla se inhibitio n FA OXIDATION FA transfer to mitoch. carnitin palmitoy l acyl transfer ase activati on

13. TÁMOP-4.1.2-08/1/A-2009-0011 Fat mass MaleFemale 18-y18%33% 85-y36%44% Muscle mass 20-40% loss  SARCOPENIA Fat, muscle and aging

14. TÁMOP-4.1.2-08/1/A-2009-0011 Body weight and adiposity index in rats Body Weight or Adiposity Index Age (mo) 312182430 100 200 300 400 500 600 Adiposity Index Body Weight

15. TÁMOP-4.1.2-08/1/A-2009-0011 “Optimal” “Optimal”4.5 kg rise (<6%) (30-y period) Reality RealityWhite male9.7 kg mean BMI ~30 or >30 Black male10.1 kg (n = 16,000) White female12.0 kg Black female20.8 kg “Optimal” and real rise of body weight in a 30-y period

16. TÁMOP-4.1.2-08/1/A-2009-0011 Body Mass Index Body Weight (kg) Height (m) 2 = 20- 25

17. TÁMOP-4.1.2-08/1/A-2009-0011 AGE at startBW-change MALEFEMALE 25–45-y+ 3.4%+ 5.2% 45–65-yno ch.no ch. 65–75-y- 4.1%- 6.3% Bodyweight change (course of 9y)

18. TÁMOP-4.1.2-08/1/A-2009-0011 BMI associated with lowest mortality (nadir of curve) Age groupBMI 20-2921.4 30-3921.6 40-4922.9 50-5925.8 60-6926.6 U-shaped relationship between BMI and mortality ratio Men’s mortality ratio (× 100) 50 >210 190 170 150 130 110 90 70 Body Mass Index (kg/m 2 ) 151821242730333639151821242730333639 >210 190 170 150 130 110 90 70 50 1518212427303336

19. TÁMOP-4.1.2-08/1/A-2009-0011 The effect of age on the BMI associated with the lowest mortality men women 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. 2626 24 22 20 18 30304050506060 Age (yrs) Body Mass Index (wt/ht 2 ) 207070 2828

20. TÁMOP-4.1.2-08/1/A-2009-0011 BMI associated with the lowest mortality Age (years)MaleFemale 20-2921.419.5 30-3921.623.4 40-4922.923.2 50-5925.825.2 60-6926.627.3 Increased proportion of fat (♂ 36%, ♀ 44%) Height  ! Normal values may be different (calculations?)