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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.
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SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES
«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 » SARCOPENIA: Origins 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
1988 in Albuquerque « Sarcopenia » In Greek: « Sarx » is Flesh and « Penia » is « Loss » 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? 19941st 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:definition 2003 Causes Atrophy and loss of individual muscle cellslinked to diminished:- synthesis of muscle proteins- function of mitochondria GREENLUND LJ et al Mech Ageing Dev 2003; 124: 287
Consequences SARCOPENIA: definition 2006 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 Ageing process Chronic health conditions Constitutional factors Living habits Living conditions CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7
Risk factors of Sarcopenia Ageing process Chronic health conditions Constitutional factors 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 elegansBehavioural 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 4days 18days Cross section of the pharynx HERNDON LA et al Nature 2002; 419: 808-14
SARCOPENIA in Caenorhabditis elegans 4days 18days Genetic heterogeneity Mitrochondrial DNA mutations Stochastic damage Rate of damage accumulation Cross section of the pharynx HERNDON LA et al Nature 2002; 419: 808-14
Risk factors of Sarcopenia 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 Constitutional factors Female gender Low birth rate Genetic susceptibility Living habits Malnutrition Low protein intakeAlcohol abuse Smoking Physical inactivity Living conditions Starvation Bed rest /immobility /deconditioning Weightlessness 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 functionoccurs at the rate of 1-2% per yearafter the age of 30 yearsandaccelerates 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 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 Constitutional factors Female gender Low birth rate Genetic susceptibility Living habits Malnutrition Low protein intakeAlcohol abuse Smoking Physical inactivity Living conditions Starvation Bed rest /immobility /deconditioning Weightlessness Cancer ?Chronic inflammatory disease ? 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
Voluntary Food restriction Increased exercise Involuntary Starvation Cachexia AnorexiaSarcopenia Weight loss in older persons:Causes THOMAS DR Clin Nutr 2007; 26: 388-99
Weight loss in older persons:3 categories Malnutrition in aged adults STARVATION: Pure protein-energy deficiency(reduction of both fat and fat-free mass) THOMAS DR Clin Nutr 2007; 26: 388-99
Malnutrition: definition 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 CACHEXIA:Severe wasting accompanying disease states such as cancer or immunodeficiency (reduction of both fat and fat-free mass) STARVATION: Pure protein-energy deficiency(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 (…) Alteringquality of life FEARON KC et al Clin Nutr 2006; 83: 1345-50
Food intake Advanced stages of various conditions / illnesses Hypermetabolism Pro-inflammatory cytokines mass MUSCLE strength CACHEXIA Adapted from THOMAS DR Clin Nutr 2007; 26: 388-99
Weight loss in older persons:3 categories CACHEXIA:Severe wasting accompanying disease states such as cancer or immunodeficiency (reduction of both fat and fat-free mass) STARVATION: Pure protein-energy deficiency(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 Complexmultifactorial processfacilitated by a combination ofvoluntary and involuntary factorsincluding 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 MORLEY JE et al Nutrition 2008; 24: 815-9
Disuse : lack of gravity, bed rest or insufficient exercise Inadequate diet Hormonal dysregulations Food intake Advanced stages of various conditions / illnesses Hypermetabolism Pro-inflammatory cytokines mass MUSCLE strength CACHEXIA AGEING SARCOPENIA 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 ? Physical Frailty Riskfactors • Body protein content • Thermo regulation • Insulin resistance • Immunity Infections • Constitutional factors • Female gender • Low birth rate • Genetic susceptibility • Ageing • Increased muscle turnover • Reduced number of muscle cellsHormonal deregulation • Changes in nervous system • Mitochondrial dysfunction • Peripheral vascular flow • Living habits • Malnutrition • Low protein intakeAlcohol/ 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 • Axial muscular tonus Falls • Masticator force • Venous flow • Osteopenia / fractures SARCOPENIA Frailty Pooroutcomes Mobility Impaired gait Falls Low endurance Physical performance Disability Poor quality of life Nursing home admission Mortality Qualiy of Life 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