Muscle Histology

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Transcript Muscle Histology

Aging & Skeletal Muscle
Fatigue
David W. Russ, PT, Ph.D.
Ohio University
School of Physical Therapy
Skeletal Muscle
“Without skeletal muscle, there is no
physical therapy.”
--Eugene Michels
Muscle Fatigue
Definitions:
#1 Change in
maximum forcegenerating capacity
of muscle with use
#2 Ability to
maintain required
or expected force
during repetitive
and/or prolonged
use – Task Failure
Muscle Fatigue: Definition 1
 Maximum Effort
 Or electrically-stimulated
 Isolated muscle or
muscle group
 Isometric or dynamic
 Sustained or intermittent
 Fixed time of exercise
 Relative (percentage) 
 Degrees of fatigue
Top: Lanza et al, 2004
Bottom: Stevens et al, 2001
Muscle Fatigue: Definition 2
 Typically submaximal
 Potentially any
functional or exercise
task
 Output is kept fixed,
time to task failure is
principal variable
 Fatigue is binary
 For certain protocols,
Definitions 1 & 2 can
be combined
Cheng et al, 2003
Loss of Force
Common factor in each definition
How is muscle force generated?
Pretty complicated…
Central Drive
Recruitment
Rate Coding
Peripheral
Excitation
Signal
Modulation
Ascending/
Descending
inputs
Crossbridge Formation
FORCE!
N.M. Transmission
T-tubule Propagation
Calcium Release
TnC Binding
Muscle Fatigue
“Fatigue makes cowards of us all.”
• V. Lombardi
Multiple sites of failure
Multiple potential mechanisms
Task specificity
Single mechanism not likely
Impact of Muscle Fatigue
 Quadriceps strength
 Transient loss of
was a significant
strength
factor in completion of
 Reduced muscular
ADLs in 16 frail
endurance was
elderly (Brown, et al., 1995)
significantly
 Lower extremity
associated with a
power positively
history of falls in
older women (Schwender predicted functional
et al., 1997)
independence in
community-dwelling
elderly (Bean et al., 2002, Suzuki et
al., 2001)
Functional Outcomes
 Strength is associated with higher
performance on tests that are used as
predictors of function (6 min walk, Timed
get-up-and-go, etc.)
 Petrella et al, 2004
 Visser et al, 2000
 Judge et al, 1996
Studies of Muscle Fatigue
 Older subjects
 (65-85 yrs)
 Matched for
physical activity
 Dorsiflexors
 Isometric
• Submax – “ramp”
• MVC
• 50% and 70%
duty cycle
 Dynamic
• Isokinetic (90 s-1)
 Outcome measures
 MVC force
• Also power for dynamic
 Central Activation
 Peripheral
Excitability/NMJ
 Contractile Properties
 Age-related
differences
 Baseline
 Changes with fatigue
Fatigue Data
Russ et al., 2008
Kent-Braun et al.,
2002
Lanza et al., 2004
Central Activation Testing
200
2.00
170
1.50
Force (N)
0.50
110
0.00
80
-0.50
50
-1.00
20
-10200
-1.50
700
1200
1700
2200
2700
-2.00
2.00
140
1.50
1.00
0.50
80
0.00
50
-0.50
-1.00
20
-1.50
-10200
1200
2200
3200
4200
-2.00
EMG (mV)
110
EMG (mV)
1.00
140
Force (N)
 No study showed age-related
deficits
 Testing is not simple to do in
the clinic
Peripheral Excitability
 M-wave
 Compound Muscle
Action potential
(CMAP)
 Amplitude & Area
 Again, age appears
unimportant
12.00
8.00
4.00
0.00
250
350
450
550
650
750
850
-4.00
-8.00
emg (mV)
6.00
3.00
0.00
70
-3.00
90
110
130
150
170
Contractile Properties
Stimulated contractions
Twitches or trains
Contraction time
Half-relaxation time
Maximum rates scaled
for force
• force development
(+df/dt)
• relaxation (-df/dt)
Twitch Potentiation
Contractile properties and
muscle fiber type
Contractile property data are consistent
with global shift to slow, Type I myosin
heavy chain
• Correlation between fatigue resistance and force
relaxation
Type I fibers are fatigue resistant
Also slower, reduce power
Evidence for increase in Type I fiber area
&/or number with age
Likely muscle specific
Generalizability
 Healthy, older
subjects
 Minimal medications
 No co-morbidities
 Sedentary, but
activity matched
 Muscle specificity
 Results corroborated
in other muscles
• Stevens et al 2001;
Allman & Rice, 2004
 Few data in upper
extremities
 Task specificity &
Function
 Increased time to
task failure with age
(endurance)
• Hunter et al., 2005
 May not relate to
whole body exercise
• Reduced cardiac
output with age
So why do older adults
complain of fatigue?
Reduced physical activity
Muscle oxidative capacity maintained
relative to young when activity is
comparable
Strength relative to function in the
environment
Although more fatigue-resistant, elders
are weaker (15-25% MVC deficits)
Absolute vs. relative tasks
Strength, Fatigue &
Functional performance
 Younger subject
 Quads produce
800N
 Needs 300N to 
stairs
 Fatigues 60%
 Can produce 320N
and still perform
task
 Older Subject
 Quads produce
400N
 Needs 300N to 
stairs
 Fatigues 30%
 Can only produce
280N – task cannot
be performed
Aging & Muscle Fatigue
 Studies that control for physical activity
tend to indicate that older subjects
fatigue no more, and perhaps less than
young subjects.
 Submaximal and functional fatigue tasks
may require a greater percentage of
exercise capacity of older subjects and
produce greater fatigue/earlier task
failure
Exercise Interventions
 Endurance Exercise:
 May not be an issue from the aspect of
muscle fatigue
• Older muscle tends to be fatigue resistant
• Will mitigate the effects of disuse, but probably not
aging per se
 Plenty of other good reasons to do it
• Cardiovascular
• Insulin Sensitivity
 Strength training is probably more of an issue
Exercise Interventions
Focus on strength not size
Sarcopenia is real
However weakness tends to exceed loss of
mass
Capacity for hypertrophy persists with age
• Blunted – work more for smaller gains
• Resistance exercise increases mixed muscle
protein synthesis (Balogapal, et al., 2001; Hasten et al., 2000; Yarasheski et
al., 1993)
• “Functional Resistance” protocol increased
myofibrillar area (Cress et al., 1996)
Central Drive
Recruitment
Rate Coding
Peripheral
Excitation
Signal
Modulation
Ascending/
Descending
inputs
Crossbridge Formation
FORCE!
Potential
areas of
action
Calcium Release
TnC Binding
N.M. Transmission
T-tubule Propagation
Many Thanks
Jane Kent-Braun
Ian Lanza
Danielle Wigmore
Ted Towse