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
NUTRITION,
PHYSICAL STATUS,
BODY COMPOSITION, SARCOPENIA
PART 2
Erika Pétervári and Miklós Székely
Molecular and Clinical Basics of Gerontology – Lecture 4
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
What is the consequence of
• body weight gain in middle-aged individuals?
• the anorexia/cachexia in old populations?
Consequences
Changes in body composition with age
The 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.
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 composition
with age
Fat, fat-free mass and cell mass of males 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 33
37
42
18
89 33 44
72 54 13
18–25 25–35 35–45 45–55 55–65 65–85
Age (years)
Absolute weight (kg)
10 20 30 40 50 60
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
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
Anorexia
(leads to sarcopenia)
• frailty
• functional disorders
• cognitive disorders
• decubitus (bed-sore, pressure ulcer)
• hip fractures
• quality of life
• mortality
Pathogenesis and functional vs. metabolic consequences of sarcopenia
SARCOPENIA Decreased
food intake
Impaired ADLS Malnutrition
Cytokines
Increased oxidative stress
Low testosterone, estrogen, GH, IGF-1
Decreased physical activity
GH = growth hormone;
IGF-1 = insulin-like growth factor-1;
BMR = basal metabolic rate;
ADLS = activities of daily living
Decreased walking speed
Impaired
balance Osteoporosis Falls Decreased
BMR
Impaired thermoregulation
Decreased physical activity
Energy deficit
Energy excess
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 stress Positive
effects
Negative effects
Longevity
Cancer
Autoimmune disease
Oxidative stress
Parenchymal cell number
Loss of function Starvation
Death
Regulated diet
↑ Calories
Main mechanisms which lead to
• weight gain of middle-aged groups
• anorexia of the old
Mechanisms
Dysorexia in the elderly: insufficient adaptation to overfeeding
Regulatory disorder!
Phase 2 Overfeeding Body Weight Change During and After Overfeeding (kg)
–1
Phase 3 Ad Libitum Study Day
Lowest 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 Energy Intake (% of Weight-Maintenance Value)
–3
Highest Weight 0
–1 1 2
20 29 41 77
–2
Dysorexia in the elderly: insufficient adaptation to underfeeding
Regulatory disorder!
Phase 2 Underfeeding Body Weight Change During and After Underfeeding (kg)
Phase 3 Ad Libitum Study Day
Younger Men Older Men
Energy Intake (% of Weight-Maintenance Value)
140
1 130
120 110 100 90 80 70 60
Time After Underfeeding (d)
2 3 4 5 6 7 8 9 10
*
* *
Components of energy balance
FI MR HL
Tc Feeding
state
Nutritional state Body weight
FI = food intake
MR = metabolic rate HL = heat loss
Tc = core temperature
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
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
• depression
Physical 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
Frequent 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)
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)
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
Regulation of FI and MR
Short-term regulation 1 Nutrients
2 Metabolites
3 Gastrointestinal hormones 4 Neural signals
Long-term regulation 1 Insulin
2 Leptin
Hypothalamic regulation of FI
NPY/AgRP neuron
Orexigenic pathway
POMC neuron Ghrelin
Leptin Anorexigenic
pathway
Activates NPY
release AgRP release
Inhibits
Arcuate nucleus Activates
MSH release
MC4 receptors Inhibititon of
melanocortin pathways
Paraventicular nucleus
Age-related changes in the regulation
In 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
Age-related changes in 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.
