Muscle mass and strength

1
Muscle mass and strength

• Muscle mass is the primary determinant of
  strength
• Obese individuals have higher lean mass therefore
  are stronger than thinner people
• Men have proportionally more lean than women thus
  are stronger at the same weight
• Sarcopenia, the loss of muscle mass is the major
  determinant of the loss of strength with age.

2
Muscle strength across the lifespan
3
Strength declines across age groups 70-79 Health
ABC
Torque (Nm)
Age
4
Changes in muscle with age

• Loss of muscle fibers
• Loss of motor neurons at the spinal cord level
• Reduction in type II fibers from 60 to 30
• Increased infiltration of muscle with fat

5
Changes in muscle metabolism with age

• Increase in mitochondrial DNA mutation
• Decline in muscle mitochondrial protein synthesis
  (40)
• Decreased oxidative phosphorylation and ATP
  generation
• Results in fatigability
• Decline in myosin heavy chain synthesis
• Major protein involved in ATP and conversion of
  chemical to mechanical energy

6
Sarcopenia What is driving the process?

• Chronic inflammation?
• Acute inflammation anorexic - catabolic state
• Relationship to cancer and cardiac cachexia?
• Decline in anabolic hormones?
• GH/IGF-1
• Decline in sex steroid hormones
• Free testosterone
• DHEA
• Fading effectiveness of insulin
• Loss of innervation?

7
Muscle Quality Loss of strength greater than
loss in muscle mass (Health ABC)
Nm of torqueper cm2 muscle area
Age
8
Muscle quality

Strength
Function
Lean mass/muscle

?
_
Fat mass
9
Skeletal Muscle fat
Less More Most
10
Histochemical Staining of Neutral Fat Content
within Skeletal Muscle Fibers
11
Muscle area and attenuation are both inversely
associated with age The Health ABC Study
50
Men
180




Women
160
45
140
40
Mid-thigh attenuation (HU)
Mid-thigh CSA (cm2)
120
35
100
30
80
60
25




lt71
71-72
73-74
75-76
77-78
79-80
lt71
71-72
73-74
75-76
77-78
79-80
Age (y)
Age (y)
Goodpaster, BH. J Appl Physiol 2001902157-2165.
12
What About the Quality of Muscle?


1.3
1.2
1.1
Specific force (Nmcm-2)
1.0
0.9
0.8
0.7
lt 30.9
31.0-35.5
35.6-40.
gt 40.4


Muscle Attenuation (HU)
13
Metabolic ObesityIntermuscular fat and
Visceral fatAssociations with Fasting Insulin
by BMI strata
Men
Women
Standardized beta
BMI
BMI
14
Lower extremity function is worse with higher fat
and lower muscle area Health ABC



Plt0.01


Lower-extremity performance

Tertiles of total body fat
Tertiles of mid-thigh muscle area
Visser M, et al, JAGS, in press
15
What is the prevalence of sarcopenia?

• No standardized definition to define an
  individual as sarcopenic
• Several proposed methods
• Lean mass
• Lean mass relative to healthy young adult
• Lean mass adjusted for height or height squared
• Lean/fat ratio
• Lean for fat mass and height

16
Prevalence of sarcopenia and sarcopenic obesity
in Health ABC - lean mass adjusted for height and
fat mass
17
Risk factors for Sarcopenia

• Likely multifactorial and complex
• Both behavioral and biological factors probably
  important
• Few identified
• New Mexico Elder Health Survey
• Age, income, low activity, smoking, lung disease
  (Baumgartner, 1998)
• Higher SHBG ( Baumgartner, 2001)
• Health ABC
• Age, physical activity, smoking in men, cancer
  and number of chronic conditions

18
Prevention approaches

• Maintain or increase lean mass
• Avoid weight loss
• Anabolic hormones (GH - IGF-1, Testosterone,
  DHEAs)
• Block cytokines (TNF alpha, Il-6?)
• Nutritional approaches - ranging from creatine to
  caloric restriction
• Maintain or increase muscle quality
• Improve metabolic capacity of muscle
• Decrease loss of type 2 fibers
• Strength training

19
Clinical trials to prevent sarcopenia

• Testosterone, DHEA
• Both result in very small increases in lean mass
  and strength with side effects limiting use
• GH, GH secretagogues
• Slight increase in mass without increase in
  strength
• Exercise
• Minimal increase in mass, but large increase in
  strength

20
The role of exercise in the prevention of
sarcopenia
50

150
45

40
140
35
30
130
Knee Strength (kg)
25
Area (cm2)
20
120
15
10
110
5
0
100
Right Left
0 12 Weeks of Resistance
Training
Frontera et al. J. Appl. Physiol., 1988
21
Lessons from observations of regarding sarcopenia
and muscle quality

• Preserving lean mass is likely the major key to
  preserving strength
• The quality of the muscle is also important - fat
  infiltration impairs muscle quality
• Both quantity and quality are important targets
  for the preservation of function in older age

22
Conclusions

• Methodologic advances in the ability to quantify
  muscle mass and fat distribution have been key to
  progress
• More work is now needed to determine risk factors
• Preventive interventions will be depend in part
  on these findings
• Current strategies
• Avoid weight loss
• Exercise

23
End

• Anne B. Newman, MD, MPH
• Sarcopenia in Older Adults
• August 19th
• University of Pittsburgh School of Medicine
• Pittsburgh, PA, 15213
• 412-624-4012
• anewman_at_pitt.edu