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 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 Erika Pétervári and Miklós Székely Molecular and Clinical Basics of Gerontology – Lecture 3 NUTRITION, PHYSICAL STATUS, BODY COMPOSITION, SARCOPENIA PART 1 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 TÁMOP-4.1.2-08/1/A-2009-0011 Lean body mass (LBM) and fat mass (FM) LBM FM 20-y 60 + 13 = 73 kg 70-y 48 + 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 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 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; 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 TÁMOP-4.1.2-08/1/A-2009-0011 Shakespeare: As you like it TÁMOP-4.1.2-08/1/A-2009-0011 Body composition – energy stores Body Fat Ranges for Standard Healthy Overfat Obese Adults 1 Underfat Female 2039 Age 40-59 60-79 0% 10% 20% 30% 40% Male 20-39 Age 40-59 60-79 Underfat Healthy Overfat 1 Based on NIH/WHO BMI Guidelines. Obese 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 years 55-65 years 65-80 years 8-9 kg/decade 1-2 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 years 75 years 16 – 25 % 28 – 41 % males – females 12 – 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 TÁMOP-4.1.2-08/1/A-2009-0011 Adipogenesis and aging Does aging make fat go MAD? (During aging certain cell types degenerate and lipids accumulate in non-adipose tissues.) Impaired adipogenesis and fat tissue function with aging TÁMOP-4.1.2-08/1/A-2009-0011 Fundamental aging processes (reactive oxygen species, telomeres, other) cytokines, cellular stress LIP CHOP C/EBP PPAR fatty acid handling, glucose metabolis m DifferentiationDependent Genes Fat distribution with aging Preadipocyt es Osteobla sts Mesenchymal Muscle adipocytesatellite like cells default Macrophages (MAD) cells Other mesenchymal cells AGING TÁMOP-4.1.2-08/1/A-2009-0011 Fat in fat depots Fat outside fat depots Insulin sensitivit y Cytokines (TNFα, IL6) Peroxisome proliferatoractivating receptor (PPAR ) FABP TÁMOP-4.1.2-08/1/A-2009-0011 Adipose FFA FA storage (FABP) FA oxidation (UCP3) FFA Liver gluconeogenesis (PEPCK) PPAR Muscle glucose oxidation (PDK4) FA oxidation (UCP3) insulin Macrophage oxLDL uptake(CD36) CH efflux (LXR and ABCA1) sensitization glucose lowering triglyceride lowering antiatherosclerotic fatty acid binding protein UCP uncoupling protein LXR liver-X-receptor ABCA1 ATP-binding cassette A1 PDK4 pyruvatdehydrogenase kinase, isoenzyme 4 PEPCK TÁMOP-4.1.2-08/1/A-2009-0011 Fat metabolism LEPTIN FA OXIDATION cAMP activated prot.kina se FA transfer to mitoch. ac CoA carboxyla se inhibitio n carnitin palmitoy l acyl transfer ase TÁMOP-4.1.2-08/1/A-2009-0011 Fat, muscle and aging Fat mass Male Female 18-y 18% 33% 85-y 36% 44% Muscle mass 20-40% loss SARCOPENIA TÁMOP-4.1.2-08/1/A-2009-0011 Body weight and adiposity index in rats Body Weight or Adiposity Index 600 500 400 300 Body Weight Adiposity Index 200 100 3 12 18 Age (mo) 24 30 TÁMOP-4.1.2-08/1/A-2009-0011 “Optimal” and real rise of body weight in a 30-y period “Optimal” period) Reality 4.5 kg rise (<6%) White male (30-y 9.7 kg mean BMI ~30 or >30 Black male 10.1 kg (n = 16,000) White female12.0 kg Black female20.8 kg TÁMOP-4.1.2-08/1/A-2009-0011 Body Mass Index Body Weight (kg) Height (m)2 = 2025 TÁMOP-4.1.2-08/1/A-2009-0011 Bodyweight change (course of 9y) 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% U-shaped relationship between BMI and mortality ratio >210 Men’s mortality ratio (× 100) TÁMOP-4.1.2-08/1/A-2009-0011 190 170 150 130 110 90 70 50 151821242730333639 >210 190 BMI associated with 170 lowest mortality 150 (nadir of curve) 130 Age group BMI 110 20-29 21.4 90 30-39 21.6 70 40-49 22.9 50 50-59 25.8 1518212427303336 39 151821242730333639 Body Mass Index (kg/m2) 60-69 26.6 The effect of age on the BMI associated with the lowest mortality 28 Body Mass Index (wt/ht2) TÁMOP-4.1.2-08/1/A-2009-0011 The regression lines were computed separately for men and for women. 26 24 22 20 18 20 30 40 50 Age (yrs) 60 70 Note that there is a strong effect of age on the BMI associated with the lowest mortality and that the TÁMOP-4.1.2-08/1/A-2009-0011 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 !