Towards a new management
of
sarcopenia & frailty
SARCOPENIA
SARCOPENIA
Origins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
SARCOPENIA: Origins
«There is probably
no decline in structure and function
more dramatic than
the decline in lean body mass or muscle mass
over the decades of life »
Relationship between lean body mass and strength

Origins of falls, fractures, loss independence
1988 in Albuquerque  « Sarcopenia »
In Greek: « Sarx » is Flesh and « Penia » is « Loss »
ROSENBERG IH Am J Clin Nutr 1989; 50: 1231-3
&
ROSENBERG IH J Nutr 1997; 127: 990S-1S
SARCOPENIA: Origins
1988 in Albuquerque  « Sarcopenia »
In Greek: « Sarx » is Flesh and « Penia » is « Loss »
« Age-related loss of muscle mass and function »
Is it a process of normative ageing?
When does this become a disease state?
Can this phenomenon be influenced?
1994
1st Sarcopenia Symposium - NIA
ROSENBERG IH Am J Clin Nutr 1989; 50: 1231-3 & ROSENBERG IH J Nutr 1997; 127: 990S-1S
SARCOPENIA
Origins of the term
Different proposed definitions
Causes of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
SARCOPENIA:
definition 1997
Involuntary loss
of
skeletal muscle mass
that occurs
with advancing age
ROSENBERG IH J Nutr 1997; 127: 990S-1S
SARCOPENIA
SARCOPENIA:
definition 2003
Causes
Atrophy and loss
of
individual muscle cells
linked to diminished:
- synthesis of muscle proteins
- function of mitochondria
GREENLUND LJ et al Mech Ageing Dev 2003; 124: 287
SARCOPENIA: definition 2006
Consequences
Age-associated
loss of skeletal muscle mass,
postulated to be a major factor in
the strength decline with ageing
Moreover, sarcopenia is related to:
- functional impairment
- disability
- falls
- loss of independence
GOODPASTER BH et al
J Gerontol Med Sci
2006; 61A: 1059-64
SARCOPENIA:
structures of current
definitions
CAUSES (and sometimes physiopathology):
Age, diet, disuse and « Combination »
Loss of skeletal muscle mass
Loss of strength
CONSEQUENCES:
Falls, functional decline, disability,
loss of independence and mortality
SARCOPENIA
Origins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGE
Risk factors of Sarcopenia
Constitutional
factors
Ageing process
Chronic health
conditions
Living habits
Living
conditions
CRUZ JENTOFT A et al
Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Risk factors of Sarcopenia
Constitutional
factors
Ageing process
Chronic health
conditions
Female gender
Low birth rate
Genetic susceptibility
Living habits
Living
conditions
CRUZ JENTOFT A et al
Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
SARCOPENIA in Caenorhabditis elegans
Behavioural phenotypes of ageing
12 days after a synchronized egg lay  40 wild types animals
A: Vigorous movement
B: Uncoordinated locomotion
C: Head and/or tail movements if stimulated
HERNDON LA et al Nature 2002; 419: 808-14
SARCOPENIA in Caenorhabditis elegans
Cross section of the pharynx
4days
HERNDON LA et al Nature 2002; 419: 808-14
18days
SARCOPENIA in Caenorhabditis elegans
Genetic heterogeneity
Mitrochondrial
mutations
Cross
section ofDNA
the pharynx
Stochastic damage
Rate of damage accumulation
4days
HERNDON LA et al Nature 2002; 419: 808-14
18days
Risk factors of Sarcopenia
Constitutional
factors
Female gender
Low birth rate
Genetic susceptibility
Living habits
Malnutrition
Low protein intake
Alcohol abuse
Smoking
Physical inactivity
Living
conditions
Starvation
Bed rest /immobility
/deconditioning
Weightlessness
Ageing process
Increased muscle turnover
 Catabolic stimuli
.  Protein degradation
. Subclinical inflammation
 Anabolic stimuli
.  Protein synthesis
Reduced number of muscle cells
 Myostatin ( recruitment)
 Apoptosis
Hormonal deregulation
 Testosterone, DHEA production
 Estrogen production
 1-25 (OH)2 vitamin D
 Thyroid function
 Growth hormone, IGF-1
 Insulin resistance
Changes in nervous system
 CNS input (loss of α-motor
neurons)
Neuro-muscular disjunction
Mitochondrial dysfunction
 Peripheral vascular flow
CRUZ JENTOFT A et al
Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Sarcopenia speed
Involuntary degenerative loss
of
skeletal muscle mass and function
occurs at the rate of
1-2% per year
after the age of 30 years
and
accelerates with advancing age
Quoted in TIMMERMAN KL et al Curr Opin Clin Nutr Metab Care 2008;11:45-9.
Skeletal Muscle Mass (SMI) & Ageing
SMI = Muscle mass/body mass x 100
Man 38 y.o.
Man 78 y.o.
Risk factors of Sarcopenia
Constitutional
factors
Female gender
Low birth rate
Genetic susceptibility
Living habits
Malnutrition
Low protein intake
Alcohol abuse
Smoking
Physical inactivity
Living
conditions
Starvation
Bed rest /immobility
/deconditioning
Weightlessness
Ageing process
Increased muscle turnover
 Catabolic stimuli
.  Protein degradation
. Subclinical inflammation
 Anabolic stimuli
.  Protein synthesis
Reduced number of muscle cells
 Myostatin ( recruitment)
 Apoptosis
Hormonal deregulation
 Testosterone, DHEA production
 Estrogen production
 1-25 (OH)2 vitamin D
 Thyroid function
 Growth hormone, IGF-1
 Insulin resistance
Changes in nervous system
 CNS input (loss of α-motor
neurons)
Neuro-muscular disjunction
Mitochondrial dysfunction
 Peripheral vascular flow
Chronic health
conditions
Cognitive impairment
Mood disturbances
Diabetes mellitus
Heart failure
Liver failure
Renal failure
Respiratory failure
Osteoarthritis
Chronic pain
Obesity
Catabolic effects of
drugs
Cancer ?
Chronic inflammatory
disease ?
CRUZ JENTOFT A et al
Curr Opin Clin Nutr Metab Care
SARCOPENIA
Origins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
Weight loss in older persons:
Causes
•Voluntary

•Involuntary

Food restriction
Starvation
Cachexia
Increased exercise
Anorexia
Sarcopenia
THOMAS DR Clin Nutr 2007; 26: 388-99
Weight loss in older persons:
3 categories
STARVATION: Pure protein-energy deficiency
(reduction of both fat and fat-free mass)
Malnutrition in aged adults
THOMAS DR Clin Nutr 2007; 26: 388-99
Malnutrition: definition
1. Undernutrition resulting from insufficient food intake
2. Overnutrition caused by excessive food intake
3. Specific nutrient deficiencies
4. Imbalance because of disproportionate intake
Geriatric Medicine:
1.
Any insufficient dietary intake among essential nutrients
3.
Proteino-caloric malnutrition
KELLER HH J Am Geriatr Soc 1993; 41: 1212-8
Quoted by DONINI LM et al J Nutr Health Ageing 2007; 11: 421-32
Weight loss in older persons:
3 categories
STARVATION: Pure protein-energy deficiency
(reduction of both fat and fat-free mass)
CACHEXIA:
Severe wasting accompanying
disease states such as cancer or immunodeficiency
(reduction of both fat and fat-free mass)
THOMAS DR Clin Nutr 2007; 26: 388-99
CACHEXIA
From the Greek words Kákos (bad) and hexis (appearance or condition)
Complex syndrome combining:
- Weight loss (> 10%)
- Reduced food intake (< 1’500 Kcal /day)
- Systemic inflammation (CRP > 10 mg / l)
+ Anorexia & Weakness
Linked to the advanced stages
of various (CHRONIC) illnesses
• Cancer
• Heart failure
• Obstructive pulmonary disease
. Kidney disease
• and (…)
Altering
quality of life
FEARON KC et al Clin Nutr 2006; 83: 1345-50
Advanced stages of various conditions / illnesses
 Food intake
Hypermetabolism
Pro-inflammatory cytokines
CACHEXIA
mass 
MUSCLE
 strength
Adapted from THOMAS DR Clin Nutr 2007; 26: 388-99
Weight loss in older persons:
3 categories
STARVATION: Pure protein-energy deficiency
(reduction of both fat and fat-free mass)
CACHEXIA:
Severe wasting accompanying
disease states such as cancer or immunodeficiency
(reduction of both fat and fat-free mass)
SARCOPENIA:
Observed age-related decline in muscle mass
(reduction fat-free mass, but increase in fat mass)
THOMAS DR Clin Nutr 2007; 26: 388-99
SARCOPENIA: definition 2008
Complex
multifactorial process
facilitated by
a combination of
voluntary and involuntary factors
including the adoption of
- more sedentary lifestyle and
- a less than optimal diet
PADDON-JONES D et al Am J Clin Nutr 2008; 87: 1562S-6S
Different kinds of weight loss
Cachexia
Anorexia
Malab
sorption
Sarcopenia
Hyper
metabolism
±
±

±
Lean tissue






Fat tissue




Appetite

Anemia
Yes

±

±

=
No
No
Proteolysis
Yes
No
No
Yes
Yes
CRP
=
=
=
=
Vitamin A

=
=
Albumin

±

±
=
=
=
=
Weight loss
MORLEY JE et al Nutrition 2008; 24: 815-9

Advanced stages of various conditions / illnesses
 Food intake
Hypermetabolism
Pro-inflammatory cytokines
CACHEXIA
mass 
MUSCLE
 strength
SARCOPENIA
AGEING
Disuse :
Inadequate diet
lack of gravity, bed rest
or insufficient exercise
Hormonal dysregulations
Adapted from THOMAS DR Clin Nutr 2007; 26: 388-99
SARCOPENIA
Origins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
Table II: Sarcopenia is a geriatric syndrome
 Body protein content
 Thermo regulation
 Insulin resistance
 Immunity
 Infections
Risk factors
Constitutional factors
Female gender
Low birth rate
Genetic susceptibility
 Axial muscular tonus
 Falls
 Masticator force
 Venous flow
 Osteopenia / fractures
Ageing
Increased muscle turnover
Reduced number of muscle cells
Hormonal deregulation
Changes in nervous system
Mitochondrial dysfunction
 Peripheral vascular flow
Living habits
Malnutrition
Low protein intake
Alcohol/ smoking
Physical inactivity
Chronic health conditions
Cognitive impairment
Mood disturbances
Diabetes mellitus
Heart / liver / lung / renal failure
Osteoarthritis
Chronic pain
Drugs
Living conditions
Starvation
Bed rest /immobility /deconditioning
Weightlessness
SARCOPENIA
Frailty
 Mobility
?
Impaired gait
Falls
Low endurance
 Physical performance
Poor outcomes
Disability
Poor quality of life
Nursing home admission
Mortality
 Qualiy of Life
Physical Frailty
 Care costs
CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7
SARCOPENIA
Origins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
SARCOPENIA
FRAILTY
REVERSIBILITY
NEED of
. A consensual working definition
. Quantitative diagnostic tools
. Promising treatment options
Many thanks for
your kind invitation