sarcopenia towards a new management of sarcopenia & frailty
TRANSCRIPT
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SARCOPENIA
Towards a new management of
sarcopenia & frailty
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SARCOPENIAOrigins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
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SARCOPENIA: Origins
Relationship between lean body mass and strength
Origins of falls, fractures, loss independence
ROSENBERG IH Am J Clin Nutr 1989; 50: 1231-3 & ROSENBERG IH J Nutr 1997; 127: 990S-1S
1988 in Albuquerque « Sarcopenia »
In Greek: « Sarx » is Flesh and « Penia » is « Loss »
«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 »
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SARCOPENIA: Origins
« 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?
ROSENBERG IH Am J Clin Nutr 1989; 50: 1231-3 & ROSENBERG IH J Nutr 1997; 127: 990S-1S
1988 in Albuquerque « Sarcopenia »
In Greek: « Sarx » is Flesh and « Penia » is « Loss »
19941st Sarcopenia Symposium - NIA
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SARCOPENIAOrigins of the term
Different proposed definitions
Causes of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
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SARCOPENIA: definition 1997
Involuntary loss of
skeletal muscle mass
that occurs
with advancing age
ROSENBERG IH J Nutr 1997; 127: 990S-1S
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SARCOPENIA
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SARCOPENIA: definition 2003
GREENLUND LJ et al Mech Ageing Dev 2003; 124: 287
Atrophy and loss of
individual muscle cellslinked to diminished:
- synthesis of muscle proteins- function of mitochondria
Causes
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SARCOPENIA: definition 2006
GOODPASTER BH et al J Gerontol Med Sci 2006; 61A: 1059-64
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
Consequences
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SARCOPENIA: structures of current definitions
Loss of skeletal muscle mass
CAUSES (and sometimes physiopathology):Age, diet, disuse and « Combination »
CONSEQUENCES:Falls, functional decline, disability, loss of independence and mortality
Loss of strength
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SARCOPENIAOrigins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGE
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Risk factors of Sarcopenia
Living habits
Ageing process Chronic health conditions
Living conditions
CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Constitutional factors
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Living habits
Ageing process Chronic health conditions
Living conditions
CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Constitutional factors
Female genderLow birth rateGenetic susceptibility
Risk factors of Sarcopenia
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SARCOPENIA in Caenorhabditis elegans
Behavioural phenotypes of ageing
A: Vigorous movement
B: Uncoordinated locomotion
C: Head and/or tail movements if stimulated
12 days after a synchronized egg lay 40 wild types animals
HERNDON LA et al Nature 2002; 419: 808-14
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SARCOPENIA in Caenorhabditis elegans
HERNDON LA et al Nature 2002; 419: 808-14
4days 18days
Cross section of the pharynx
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SARCOPENIA in Caenorhabditis elegans
HERNDON LA et al Nature 2002; 419: 808-14
4days 18days
Cross section of the pharynx
Genetic heterogeneityMitrochondrial DNA mutations
Stochastic damageRate of damage accumulation
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Living habits Malnutrition Low protein intakeAlcohol abuseSmokingPhysical inactivity
Ageing process Increased muscle turnover Catabolic stimuli . Protein degradation . Subclinical inflammation Anabolic stimuli . Protein synthesisReduced number of muscle cells Myostatin ( recruitment) ApoptosisHormonal deregulation Testosterone, DHEA production Estrogen production 1-25 (OH)2 vitamin D Thyroid function Growth hormone, IGF-1 Insulin resistanceChanges in nervous system CNS input (loss of α-motor neurons) Neuro-muscular disjunctionMitochondrial dysfunction Peripheral vascular flow
Living conditions
StarvationBed rest /immobility /deconditioningWeightlessness
CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Constitutional factors
Female genderLow birth rateGenetic susceptibility
Risk factors of Sarcopenia
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Sarcopenia speedInvoluntary degenerative loss
of skeletal muscle mass and function
occurs at the rate of
1-2% per yearafter the age of 30 years
andaccelerates with advancing age
Quoted in TIMMERMAN KL et al Curr Opin Clin Nutr Metab Care 2008;11:45-9.
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SMI = Muscle mass/body mass x 100
Skeletal Muscle Mass (SMI) & Ageing
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Man 38 y.o.
Man 78 y.o.
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Living habits MalnutritionLow protein intakeAlcohol abuseSmokingPhysical inactivity
Ageing process Increased muscle turnover Catabolic stimuli . Protein degradation . Subclinical inflammation Anabolic stimuli . Protein synthesisReduced number of muscle cells Myostatin ( recruitment) ApoptosisHormonal deregulation Testosterone, DHEA production Estrogen production 1-25 (OH)2 vitamin D Thyroid function Growth hormone, IGF-1 Insulin resistanceChanges in nervous system CNS input (loss of α-motor neurons) Neuro-muscular disjunctionMitochondrial dysfunction Peripheral vascular flow
Chronic health conditions
Cognitive impairmentMood disturbancesDiabetes mellitusHeart failure Liver failureRenal failureRespiratory failure
OsteoarthritisChronic pain
Obesity
Catabolic effects of drugs
Living conditions
StarvationBed rest /immobility /deconditioningWeightlessness
CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care
2010; 13: 1-7
Cancer ?Chronic inflammatory disease ?
Constitutional factors
Female genderLow birth rateGenetic susceptibility
Risk factors of Sarcopenia
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SARCOPENIAOrigins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
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Weight loss in older persons:Causes
•Voluntary
Food restriction
Increased exercise
•Involuntary
Starvation Cachexia
AnorexiaSarcopenia
THOMAS DR Clin Nutr 2007; 26: 388-99
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Weight loss in older persons:3 categories
STARVATION: Pure protein-energy deficiency(reduction of both fat and fat-free mass)
THOMAS DR Clin Nutr 2007; 26: 388-99
Malnutrition in aged adults
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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
KELLER HH J Am Geriatr Soc 1993; 41: 1212-8Quoted by DONINI LM et al J Nutr Health Ageing 2007; 11: 421-32
Geriatric Medicine:
1.Any insufficient dietary intake among essential nutrients
3. Proteino-caloric malnutrition
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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
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CACHEXIAFrom 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
Alteringquality of life
FEARON KC et al Clin Nutr 2006; 83: 1345-50
Linked to the advanced stages of various (CHRONIC) illnesses
• Cancer• Heart failure
• Obstructive pulmonary disease. Kidney disease
• and (…)
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Food intake
mass MUSCLE strength
CACHEXIA
Hypermetabolism
Pro-inflammatory cytokines
Adapted from THOMAS DR Clin Nutr 2007; 26: 388-99
Advanced stages of various conditions / illnesses
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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
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SARCOPENIA: definition 2008
PADDON-JONES D et al Am J Clin Nutr 2008; 87: 1562S-6S
Complexmultifactorial process
facilitated by a combination of
voluntary and involuntary factorsincluding the adoption of
- more sedentary lifestyle and- a less than optimal diet
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Different kinds of weight lossCachexia Anorexia Malab
sorption
Sarcopenia Hypermetabolism
Weight loss ± ± ±Lean tissue Fat tissue Appetite = Anemia Yes ± ± No No
Proteolysis Yes No No Yes Yes
CRP = = = =Vitamin A = = = =Albumin ± ± = =
MORLEY JE et al Nutrition 2008; 24: 815-9
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Food intake
mass MUSCLE strength
CACHEXIA
Hypermetabolism
Pro-inflammatory cytokines
Adapted from THOMAS DR Clin Nutr 2007; 26: 388-99
Advanced stages of various conditions / illnesses
SARCOPENIA
Disuse :lack of gravity, bed rest or insufficient exercise
Inadequate diet
Hormonal dysregulations
AGEING
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SARCOPENIAOrigins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
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Table II: Sarcopenia is a geriatric syndrome
SARCOPENIASARCOPENIA
Constitutional factorsFemale genderLow birth rateGenetic susceptibility
AgeingIncreased muscle turnoverReduced number of muscle cellsHormonal deregulationChanges in nervous systemMitochondrial dysfunction Peripheral vascular flow
Living habitsMalnutritionLow protein intakeAlcohol/ smokingPhysical inactivity
Chronic health conditionsCognitive impairmentMood disturbancesDiabetes mellitusHeart / liver / lung / renal failureOsteoarthritisChronic painDrugs
Living conditionsStarvationBed rest /immobility /deconditioningWeightlessness CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7
Risk factorsRisk factors
FrailtyFrailty Poor outcomesPoor outcomes
MobilityImpaired gaitFallsLow endurance
Physical performance
DisabilityPoor quality of lifeNursing home admissionMortality
Axial muscular tonus Falls Masticator force Venous flow Osteopenia / fractures
Body protein content Thermo regulation Insulin resistance Immunity Infections
Care costs
Qualiy of Life
Physical Frailty
?
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SARCOPENIAOrigins of the term
Different proposed definitions
Risk factors of sarcopenia
Sarcopenia and its closest concepts
Consequences of sarcopenia
Sarcopenia & frailty: KEY MESSAGES
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SARCOPENIA FRAILTY
REVERSIBILITY
NEED of . A consensual working definition
. Quantitative diagnostic tools
. Promising treatment options
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Many thanks for your kind invitation