1. SARCOPENIA Towards a new management of sarcopenia & frailty

2. SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES

3. 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 »

4. 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 » 1994 1st Sarcopenia Symposium - NIA

5. SARCOPENIA Origins of the term Different proposed definitions Causes of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES

6. SARCOPENIA: definition 1997 Involuntary loss of skeletal muscle mass that occurs with advancing age ROSENBERG IH J Nutr 1997; 127: 990S-1S

7. SARCOPENIA

8. SARCOPENIA: definition 2003 GREENLUND LJ et al Mech Ageing Dev 2003; 124: 287 Atrophy and loss of individual muscle cells linked to diminished: - synthesis of muscle proteins - function of mitochondria Causes

9. 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

10. 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

11. SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGE

12. 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

13. 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 gender Low birth rate Genetic susceptibility Risk factors of Sarcopenia

14. 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

15. SARCOPENIA in Caenorhabditis elegans HERNDON LA et al Nature 2002; 419: 808-14 4days 18days Cross section of the pharynx

16. SARCOPENIA in Caenorhabditis elegans HERNDON LA et al Nature 2002; 419: 808-14 4days 18days Cross section of the pharynx Genetic heterogeneity Mitrochondrial DNA mutations Stochastic damage Rate of damage accumulation

17. Living habits Malnutrition Low protein intake Alcohol abuse Smoking Physical inactivity 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 Living conditions Starvation Bed rest /immobility /deconditioning Weightlessness CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7 Constitutional factors Female gender Low birth rate Genetic susceptibility Risk factors of Sarcopenia

18. 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.

19. SMI = Muscle mass/body mass x 100 Skeletal Muscle Mass (SMI) & Ageing

20. Man 38 y.o. Man 78 y.o.

21. Living habits Malnutrition Low protein intake Alcohol abuse Smoking Physical inactivity 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 Living conditions Starvation Bed rest /immobility /deconditioning Weightlessness CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7 Cancer ? Chronic inflammatory disease ? Constitutional factors Female gender Low birth rate Genetic susceptibility Risk factors of Sarcopenia

22. SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES

23. Weight loss in older persons: Causes Voluntary  Food restriction Increased exercise Involuntary  Starvation Cachexia Anorexia Sarcopenia THOMAS DR Clin Nutr 2007; 26: 388-99

24. 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

25. 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: 1212-8 Quoted 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

26. 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

27. 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 Altering quality 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 (…)

28.  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

29. 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

30. SARCOPENIA: definition 2008 PADDON-JONES D et al Am J Clin Nutr 2008; 87: 1562S-6S 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

31. Different kinds of weight loss CachexiaAnorexiaMalab sorption SarcopeniaHyper metabolism Weight loss ±± ±± ±± Lean tissue  Fat tissue  Appetite  =  AnemiaYes ±± No ProteolysisYesNo Yes CRP  ==== Vitamin A ==  == Albumin ±± ±± == MORLEY JE et al Nutrition 2008; 24: 815-9

32.  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

33. SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES

34. Table II: Sarcopenia is a geriatric syndrome SARCOPENIA Constitutional factors Female gender Low birth rate Genetic susceptibility 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 CRUZ JENTOFT A et al Curr Opin Clin Nutr Metab Care 2010; 13: 1-7 Risk factors Frailty Poor outcomes  Mobility Impaired gait Falls Low endurance  Physical performance Disability Poor quality of life Nursing home admission Mortality  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 ?

35. SARCOPENIA Origins of the term Different proposed definitions Risk factors of sarcopenia Sarcopenia and its closest concepts Consequences of sarcopenia Sarcopenia & frailty: KEY MESSAGES

36. SARCOPENIA FRAILTY REVERSIBILITY NEED of. A consensual working definition. Quantitative diagnostic tools. Promising treatment options

37. Many thanks for your kind invitation