sarcopenia towards a new management of sarcopenia & frailty

SARCOPENIA

Towards a new management of

sarcopenia & frailty

SARCOPENIAOrigins of the term

Different proposed definitions

Risk factors of sarcopenia

Sarcopenia and its closest concepts

Consequences of sarcopenia

Sarcopenia & frailty: KEY MESSAGES

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 »

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

SARCOPENIAOrigins 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

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

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

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

SARCOPENIAOrigins 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

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

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

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

SARCOPENIA in Caenorhabditis elegans

HERNDON LA et al Nature 2002; 419: 808-14

4days 18days

Cross section of the pharynx

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

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

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.

SMI = Muscle mass/body mass x 100

Skeletal Muscle Mass (SMI) & Ageing

Man 38 y.o.

Man 78 y.o.

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

SARCOPENIAOrigins 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

Food restriction

Increased exercise

•Involuntary

Starvation Cachexia

AnorexiaSarcopenia

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)

THOMAS DR Clin Nutr 2007; 26: 388-99

Malnutrition in aged adults

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

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

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 (…)

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

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

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

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

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

SARCOPENIAOrigins 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

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

?

SARCOPENIAOrigins 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