Muscle mass and strengthMuscle mass and strength

Muscle mass is the primary determinant Muscle mass is the primary determinant of strengthof strength– Obese individuals have higher lean mass Obese individuals have higher lean mass

therefore are stronger than thinner peopletherefore are stronger than thinner people– Men have proportionally more lean than Men have proportionally more lean than

women thus are stronger at the same weightwomen thus are stronger at the same weight– Sarcopenia, the loss of muscle mass is the Sarcopenia, the loss of muscle mass is the

major determinant of the loss of strength major determinant of the loss of strength with age.with age.

Muscle strength across the lifespanMuscle strength across the lifespan

Strength declines across age groups 70-79Strength declines across age groups 70-79 Health ABC Health ABC

0

20

40

60

80

100

120

140

160

70 72 74 76 78 80

MenWomen

Torque (Nm)

Age

Changes in muscle with ageChanges in muscle with age

Loss of muscle fibersLoss of muscle fibers Loss of motor neurons at the spinal cord Loss of motor neurons at the spinal cord

levellevel Reduction in type II fibers from 60% to Reduction in type II fibers from 60% to

30%30% Increased infiltration of muscle with fatIncreased infiltration of muscle with fat

Changes in muscle metabolism Changes in muscle metabolism with agewith age

Increase in mitochondrial DNA mutationIncrease in mitochondrial DNA mutation Decline in muscle mitochondrial protein Decline in muscle mitochondrial protein

synthesis (40%)synthesis (40%)– Decreased oxidative phosphorylation and Decreased oxidative phosphorylation and

ATP generationATP generation– Results in fatigabilityResults in fatigability

Decline in myosin heavy chain synthesisDecline in myosin heavy chain synthesis– Major protein involved in ATP and conversion Major protein involved in ATP and conversion

of chemical to mechanical energyof chemical to mechanical energy

Sarcopenia: What is driving the Sarcopenia: What is driving the process?process?

Chronic inflammation?Chronic inflammation?– Acute inflammation: anorexic - catabolic stateAcute inflammation: anorexic - catabolic state– Relationship to cancer and cardiac cachexia?Relationship to cancer and cardiac cachexia?

Decline in anabolic hormones?Decline in anabolic hormones?– GH/IGF-1GH/IGF-1– Decline in sex steroid hormonesDecline in sex steroid hormones

Free testosteroneFree testosterone DHEADHEA

– Fading effectiveness of insulinFading effectiveness of insulin Loss of innervation?Loss of innervation?

Muscle Quality – Loss of strength greater Muscle Quality – Loss of strength greater than loss in muscle mass (Health ABC)than loss in muscle mass (Health ABC)

0

4

8

12

16

70 72 74 76 78 80

MenWomen

Nm of torqueper cm2 muscle area

Age

Muscle qualityMuscle quality

Lean mass/muscle Strength Function

Fat mass

+ ?_

Skeletal Muscle fat

Less More Most

Histochemical Staining of Neutral Fat Content Histochemical Staining of Neutral Fat Content within Skeletal Muscle Fiberswithin Skeletal Muscle Fibers

60

80

100

120

140

160

180

Mid

-th

igh

CS

A (

cm2)

25

30

35

40

45

50

Mid

-th

igh

att

enu

atio

n (

HU

)

<71 71-72 73-74 75-76 77-78 79-80

Age (y)

<71 71-7273-74 75-76 77-78 79-80

Age (y)

MenWomen

Muscle area and attenuation are both Muscle area and attenuation are both inversely associated with age: The Health inversely associated with age: The Health

ABC StudyABC Study

Goodpaster, BH. J Appl Physiol 2001;90:2157-2165.

What About the Quality of Muscle?What About the Quality of Muscle?

0.7

0.8

0.9

1.0

1.1

1.2

1.3

Sp

ecif

ic f

orce

(N

m•c

m-2

)

< 30.9 31.0-35.5 35.6-40. > 40.4

Muscle Attenuation (HU)

MenWomen

MenWomen

““Metabolic Obesity”Metabolic Obesity”Intermuscular fat and Visceral fat:Intermuscular fat and Visceral fat:

Associations with Fasting Insulin by BMI strataAssociations with Fasting Insulin by BMI strata

00,05

0,10,15

0,20,25

0,30,35

T1 T2 T3

Intermuscular Thigh FatVisceral Abdominal Fat

00,05

0,10,15

0,20,25

0,30,35

T1 T2 T3

Intermuscular Thigh FatVisceral Abdominal Fat

BMIBMI BMIBMI

SSttaannddaarrddiizzeedd

bbeettaa

0

1

2

3

4

5

6

low medium high

highmedium

low

Lo

wer

-ext

rem

ity

per

form

ance

**

*

*

*

*

Tertilesof totalbody fat

Tertiles of mid-thigh muscle area

Lower extremity function is worse with higher fat and lower muscle area – Health ABC

Visser M, et al, JAGS, in press

*P<0.01

What is the prevalence of What is the prevalence of sarcopenia?sarcopenia?

No standardized definition to define an No standardized definition to define an individual as sarcopenicindividual as sarcopenic

Several proposed methodsSeveral proposed methods– Lean massLean mass– Lean mass relative to healthy young adultLean mass relative to healthy young adult– Lean mass adjusted for height or height Lean mass adjusted for height or height

squaredsquared– Lean/fat ratioLean/fat ratio– Lean for fat mass and heightLean for fat mass and height

Prevalence of sarcopenia and sarcopenic Prevalence of sarcopenia and sarcopenic obesity in Health ABC - lean mass obesity in Health ABC - lean mass adjusted for height and fat massadjusted for height and fat mass

Figure 2b. Prevalence of obesity(BMI>median BMI by gender), Sarcopenia (Residuals<20th percentile), and Sarcopenic-Obesity by Gender

42.941.7

37.038.3

13.011.7

7.08.4

0.0

10.0

20.0

30.0

40.0

50.0

60.0

Men Women

Pre

vale

nce

(P

erce

nt)

obese

normal

sarcopenic

sarcopenic-obese

Risk factors for SarcopeniaRisk factors for Sarcopenia

Likely multifactorial and complexLikely multifactorial and complex– Both behavioral and biological factors probably Both behavioral and biological factors probably

importantimportant

Few identifiedFew identified– New Mexico Elder Health Survey:New Mexico Elder Health Survey:

Age, income, low activity, smoking, lung disease Age, income, low activity, smoking, lung disease (Baumgartner, 1998)(Baumgartner, 1998)

Higher SHBG ( Baumgartner, 2001)Higher SHBG ( Baumgartner, 2001)

– Health ABC:Health ABC: Age, physical activity, smoking; in men, cancer and Age, physical activity, smoking; in men, cancer and

number of chronic conditionsnumber of chronic conditions

Prevention approachesPrevention approaches

Maintain or increase lean massMaintain or increase lean mass– Avoid weight lossAvoid weight loss– Anabolic hormones (GH - IGF-1, Testosterone, Anabolic hormones (GH - IGF-1, Testosterone,

DHEA’s)DHEA’s)– Block cytokines (TNF alpha, Il-6?)Block cytokines (TNF alpha, Il-6?)– Nutritional approaches - ranging from creatine to Nutritional approaches - ranging from creatine to

caloric restrictioncaloric restriction Maintain or increase muscle qualityMaintain or increase muscle quality

– Improve metabolic capacity of muscleImprove metabolic capacity of muscle– Decrease loss of type 2 fibersDecrease loss of type 2 fibers– Strength trainingStrength training

Clinical trials to prevent sarcopeniaClinical trials to prevent sarcopenia

Testosterone, DHEATestosterone, DHEA– Both result in very small increases in lean Both result in very small increases in lean

mass and strength with side effects limiting mass and strength with side effects limiting useuse

GH, GH secretagoguesGH, GH secretagogues– Slight increase in mass without increase in Slight increase in mass without increase in

strengthstrength ExerciseExercise

– Minimal increase in mass, but large increase Minimal increase in mass, but large increase in strengthin strength

The role of exercise in the The role of exercise in the prevention of sarcopeniaprevention of sarcopenia

Frontera et al. J. Appl. Physiol., 1988

05

101520253035404550

Flexion

Extension

Kn

ee S

tren

gth

(kg)

0 12

Weeks of Resistance Training

100

110

120

130

140

150pre

post

Are

a (c

m2 )

Right Left

Lessons from observations of regarding Lessons from observations of regarding sarcopenia and muscle qualitysarcopenia and muscle quality

Preserving lean mass is likely the Preserving lean mass is likely the major key to preserving strengthmajor key to preserving strength

The quality of the muscle is also The quality of the muscle is also important - fat infiltration impairs important - fat infiltration impairs muscle qualitymuscle quality

Both quantity and quality are important Both quantity and quality are important targets for the preservation of function targets for the preservation of function in older agein older age

ConclusionsConclusions Methodologic advances in the ability to quantify Methodologic advances in the ability to quantify

muscle mass and fat distribution have been key muscle mass and fat distribution have been key to progressto progress

More work is now needed to determine risk More work is now needed to determine risk factorsfactors

Preventive interventions will be depend in part Preventive interventions will be depend in part on these findingson these findings

Current strategiesCurrent strategies– Avoid weight lossAvoid weight loss– ExerciseExercise

EndEnd

Anne B. Newman, MD, MPH Anne B. Newman, MD, MPH Sarcopenia in Older AdultsSarcopenia in Older Adults August 19thAugust 19th University of Pittsburgh School of University of Pittsburgh School of

MedicineMedicine Pittsburgh, PA, 15213Pittsburgh, PA, 15213 412-624-4012412-624-4012 anewman@pitt.eduanewman@pitt.edu