Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics
This presentation is the property of its rightful owner.
Sponsored Links
1 / 51

Neural and Muscular Factors in Muscle Fatigue (Fatigability) of Older Adults: Role of Energetics PowerPoint PPT Presentation


  • 328 Views
  • Uploaded on
  • Presentation posted in: General

Neural and Muscular Factors in Muscle Fatigue (Fatigability) of Older Adults: Role of Energetics. Jane Kent-Braun, PhD Muscle Physiology Laboratory Department of Kinesiology University of Massachusetts, Amherst. Outline. Neuromuscular changes in old age

Download Presentation

Neural and Muscular Factors in Muscle Fatigue (Fatigability) of Older Adults: Role of Energetics

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Neural and Muscular Factors in Muscle Fatigue (Fatigability) of Older Adults: Role of Energetics

Jane Kent-Braun, PhD

Muscle Physiology Laboratory

Department of Kinesiology

University of Massachusetts, Amherst


Outline

Outline

  • Neuromuscular changes in old age

  • Measuring the mechanisms of human muscle fatigue in vivo

  • Basis of age-related differences in muscle fatigue

  • Integrating divergent results


Skeletal muscle function

Skeletal Muscle Function

  • strength, power(sarcopenia)

  • activation; central, peripheral

  • contractile properties(fast, slow)

  • energetics(oxidative, glycolytic)

  • fatigue resistance (fall of max. force),endurance(time to task failure)


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Neuromuscular Changes in Old Age

StructuralFunctional

↓ strength & power

↓ muscle size

 voluntary activation

↑ intra-, extra-myocellular fat

↓max. discharge rates

↓motor unit number

slowed contractile properties

↑ type I MHC content

↑ type I/type II fiber area

peripheral activation

 () oxidative capacity

 capillarity

↑ oxidative energy utilization

Fatigue Resistance?

Note: all species decrease spontaneous physical activity in old age!


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Potential Sites of Fatigue in Vivo

O2 delivery

(blood flow)

Central Activation

rate coding

recruitment

modulation

Peripheral Activation

NMJ, membrane excitability

conduction velocity

muscle cell

Contractile Function

EC coupling

Ca2+ kinetics

cross-bridge function

Metabolism

energy supply

inhibitory action

Force or Power


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

CNS

NMJ

stimulation

Central & Peripheral Activation,

Contractile Function

Activation: process by which the signal to contract is transmitted from CNS to contractile apparatus


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Assessing the Sites

Contractile

Function

Energetics

Central

Activation

Peripheral

Activation

muscle cell

Force


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Assessing the Sites

EMG

CAR

Force

0

1000

2000

3000

4000

5000

Time (s)

Contractile

Function

Energetics

Peripheral

Activation

muscle cell

Force


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Assessing the Sites

EMG

CAR

Force

m-wave

0

1000

2000

3000

4000

5000

Time (s)

Contractile

Function

Energetics

muscle cell

Force


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Assessing the Sites

EMG

CAR

Force

m-wave

0

1000

2000

3000

4000

5000

Time (s)

muscle cell

Contractile

Function

31P MRS

Force

ATP


Muscle contraction atp adp pi energy creatine kinase reaction adp pcr h atp cr

pH

Intracellular Energy Metabolism

Muscle Contraction:ATPADP+Pi+ energyCreatine kinase reaction:ADP+PCr+H+ ATP + Cr

PCr

Calculate:

pH

[ADP]

[H2PO4-]

[AMP]

γ-ATP

α-ATP

Pi

β-ATP


In vivo muscle energetics 31 p mrs

In Vivo Muscle Energetics: 31P MRS

  • 4T whole-body system (Yale)

  • 2-12 s resolution

  • metabolites of fatigue

  • oxidative function

  • glycolytic flux

recovery

contraction

rest


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Assessing the Sites in Vivo

EMG

CAR

Force

m-wave

0

1000

2000

3000

4000

5000

Time (s)

31P MRS

Electrical stim.

muscle cell

ATP

Force


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

4 Tesla

MRS

  • In vivo and simultaneous

  • measures of:

  • activation

  • force, contractile

  • properties

  • energetics, acidosis

  • intracellular PO2

  • perfusion


Age based differences in muscle fatigue

Physical Activity Array

Foulis, submitted

Age-Based Differences in Muscle Fatigue

Study groups:

  • young (21-40y), older (65-80y)

  • healthy (balanced by sex)

  • sedentary, activity-matched

  • older, physically-impaired

    Contraction protocols:

  • Maximal and submaximal contractions

  • Isometric and dynamic contractions

  • Effect of duty cycle (contraction/relaxation, 10 s)

  • Effect of blood flow

  • Effect of muscle group


Study 1 fatigue during incremental contractions effect of old age

Study #1Fatigue During Incremental Contractions: Effect of Old Age?

isometric, intermittent (40% duty cycle)

2 min stages for 16 min

increments of 10% MVC

from steady-state to fatigue

activation, contractile function, energetics


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

20 Y, 21 O

Target force

Less fatigue in old than young

Kent-Braun, 2002


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

More intracellular

acidosis in young

20 Y, 21 O

pH

Greater accumulation of Pi and H2PO4- in young


Fatigue during incremental contractions associated with h 2 po 4

OW

OM

YW

YM

Fatigue During Incremental Contractions Associated with [H2PO4-]

Kent-Braun, 2002


H mrs greater myoglobin desaturation in young

Time (min)

H+ MRS: Greater Myoglobin Desaturation in Young

Intracellular PO2

Y = 5.3 Torr

O = 7.0 Torr

(NS)

n = 17 Y

n = 18 O

Wigmore, in prep


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Fatigue Resistance in Aging

O2 delivery

(blood flow)

Central

Activation

Peripheral

Activation

muscle cell

Contractile

Function

Energetics

Force


Study 2 pathways of atp production in vivo effect of old age

Study #2Pathways of ATP Production In Vivo:Effect of Old Age?

isometric, maximal contraction for 60 s

ATP production by:

- oxidative phosphorylation (mitochondria)

- glycolysis

- creatine kinase reaction


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

40% Lower peak glycolytic rate in old during 60s MVC (p<0.001)

Lanza et al, 2005

Energetic “Capacity”

In Vivo

Similar Vmax for oxidative phosphorylation in young

and old (p = 0.67)


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Pathway

UtilizationIn Vivo

Young

Greater reliance on oxidative metabolism in healthy old

Older

Lanza, 2005


Study 3 atp production in young old oxidative preference or glycolytic limitation

Study #3ATP Production in Young & Old:Oxidative “Preference” or Glycolytic Limitation?

6 isometric, maximal contractions

intermittent (50% duty cycle; 12s/12s)

+/- ischemia

ATP flux by oxphos, glycolysis, CK


Less fatigue in old during maximal contractions

intracellular pH

Less Fatigue in Old During Maximal Contractions

Free-flow

force-time integral

40 Y, 38 O

Ischemia

12s contract, 12s relax

Lanza, 2007


Fatigue during maximal contractions associated with h 2 po 4

Free Flow

young; r = 0.88  0.05

older; r = 0.82  0.07

Ischemia

young; r = 0.90  0.05

older; r = 0.82  0.06

Fatigue During Maximal Contractions Associated with [H2PO4-]

Lanza, 2007


Higher metabolic economy in older adults during maximal isometric contractions free flow

Higher Metabolic Economy in Older Adults During Maximal Isometric Contractions (free-flow)


Study 4 is oxygen needed for fatigue resistance in the elderly

Study #4Is Oxygen Needed for Fatigue Resistance in the Elderly?

6 min intermittent, isometric MVCs

free-flow, occlusion-reperfusion

- central activation

- peripheral activation

- contractile properties


Age related difference in muscle fatigue more apparent during ischemia

Old FF

Young FF

Old IR

Young IR

Age-Related Difference in Muscle Fatigue More Apparent During Ischemia!

O < Y (p=0.02)

O < Y (p<0.01)

O = Y (p=0.07)

free-flow

reperfusion

ischemia

Chung, 2007

more central & peripheral activation failure in young during ischemia


Summary and conclusions

Summary and Conclusions

  • Increased fatigue resistance in old age, during isometric contractions, has a metabolic basis (with secondary effects on central activation).

  • Energetic and fatigue differences in young and old are independent of blood flow.

  • Chronic neural (central) and contractile (peripheral) adaptations likely play a role in altered muscle energetics.

  • Lack of age-by-sex interactions suggests the neuromuscular systems of men and women age similarly.


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

Muscular Component

Neural Component

Fiber type shift:

relative ↑ type I fiber area

↓ Maximal motor unit discharge rates

  • - Slower force

  • relaxation

  • - Force fusion at

  • lower frequency

Force produced with fewer motor unit discharges

metabolic economy higher in type I fibers

↓ metabolic demand

↑ metabolic economy

↓ accumulation of inhibitory metabolites

less fatigue

Neural and Muscular Factors May Establish Metabolic Basis of Fatigue Resistance in Healthy Older Adults

Kent-Braun, 2008


Muscular factors atp cost of twitch

Muscular Factors: ATP Cost of Twitch

tibialis anterior, mean+SE

Tevald, in progress


Integrating divergent results

Integrating Divergent Results?


Fatigue resistance endurance older humans show

Poor

Davies 1983 (e) Lennmarken 1985 Cupido 1992 (e)

Petrella 2005 (d)

Baudry 2006 (d)

McNeil 2007 (d)

Fatigue Resistance & Endurance: Older humans show…

Same

Klein 1988 (e)

Cupido 1992 (e)

Bemben 1996

Lindstrom 1997 (d)

Stackhouse 2001

McNeil 2007 (d)

Petrofsky 1975

Larsson 1978

Sperling 1980

Allman 2001

Yoon 2008

Better

Narici 1991 (e)

Bemben 1996

Ditor 2000

Chan 2000

Kent-Braun 2002

Lanza 2004 (d)

Allman 2004 (e)

Rubenstein 2005

Chung 2007

Lanza 2008

Bilodeau 2001

Hunter 2004, 2005

Mademli 2008

Yoon 2008

Fatigue

Resistance

Endurance

(e) denotes stimulated contractions

(d) denotes dynamic contractions


Effect of age on fatigue varies by contraction mode and muscle group

Effect of Age on Fatigue Varies by Contraction Mode and Muscle Group

Dorsiflexors Knee Extensors

isometric

dynamic

Lanza et al, 2004

Callahan et al, ACSM 2008


Mitochondrial capacity varies by muscle

Mitochondrial Capacity Varies by Muscle

kPCr (s-1)

TA

VL

tibialis anterior vastus lateralis

Older impaired group: SPPB ~10

Larsen, in preparation


Difference in mitochondrial capacity by muscle related to physical activity dose and health

Difference in Mitochondrial Capacity by Muscle Related to Physical Activity Dose (and Health)

Tibialis AnteriorVastus Lateralis

r = 0.29

p = 0.07

r = 0.74

p < 0.001

Muscle

Oxidative

Capacity

Daily Minutes of High-Intensity Activity

n = 44 young and older adults

Larsen et al, ACSM 2008


Physical activity arrays accelerometry

Older Sedentary

Older Impaired

Physical Activity Arrays:Accelerometry

Young Active

Young Sedentary

Zero

Sedentary

Light

Moderate

Vigorous

Foulis, submitted


Daily total physical activity

Physical Activity (counts·day-1·1000-1)

Daily Total Physical Activity

Larsen, in preparation


Neural and muscular factors in muscle fatigue fatigability of older adults role of energetics

MVPA (min·day-1)

Daily Minutes of Moderate-Vigorous Physical Activity

Larsen, in preparation


Physically impaired elders lose their fatigue resistance in the knee extensor muscles

O = Y < OI

Physically-Impaired Elders Lose Their Fatigue Resistance in the Knee Extensor Muscles

Isometric Dynamic

O < Y = OI

Callahan, in progress


Relative ability to resist fatigue in old age dependence on contraction velocity

healthy old

impaired old

Relative ability to resist fatigue in old age: Dependence on contraction velocity?

80%

  • intensity

  • duty cycle

  • muscle

torque

or

power

at fatigue

(% baseline)

young

velocity very fast

0

Is greater fatigue resistance during isometric contractions in elderly eliminated or reversed during dynamic contractions?


Absolute amount of fatigue implications for physical function

healthy old

impaired old

Absolute Amount of Fatigue: Implications for Physical Function?

torque

or

power

(Nm∙s-1)

young

functional

deficit

velocity

Importance of baseline muscle strength!

e.g., Lindstrom et al, 1997; Milner-Brown & Miller, 1989


Progression from fatigue resistance to physical impairment

 physical activity

 muscle mass

 neural drive

 muscle power

 mitochondrial function

loss of fatigue resistance

 physical function

 relative exertion, perceived fatigue

Progression from Fatigue Resistance to Physical Impairment?

injury/disease/event/age


Collaborators

Collaborators

University of Massachusetts, Amherst

Ian Lanza, PhD David Russ, PT, PhD

Danielle Wigmore, PhD Linda Chung, MS

Damien Callahan, MSStephen Foulis, MS

Michael Tevald, PT, PhDGraham Caldwell, PhD

Yale University

Douglas Befroy, DPhilDouglas Rothman, PhD

University of California, San Francisco

Alexander Ng, PhDJulie Doyle, MS

Support

National Institute on Aging R01 AG21094, K02 AG023582

ACSM, AFAR, NASA, AHA, APTA


Future directions

Future Directions

What do we need to know?

1. What is inevitable?

- in healthy adults, with attention to activity level

- range of ages (25-95 years)

- biological aging; “what is the target?”

2. What is modifiable?

- effects of impairment/disease, medications?

- interactions between sarcopenia and fatigue?

- multi-system studies (neural, contractile, energy…)

- context of independent living


Design considerations

Design Considerations

A. Study populations

health, activity, age, sex

old, older, oldest?

B. Protocols

- capacity of the system (“biological aging”), or

- typical conditions (“representative of population”)?

- mode, intensity, frequency, duration, duty cycle

- muscle(s)

- definitions; endurance,  force/power,  velocity

C. Mechanisms

how to measure?

molecular, single fiber, animal models?


Similar oxidative potential in young older adults

Similar Oxidative Potential in Young & Older Adults


Effect of contraction velocity mechanisms

Effect of Contraction Velocity: Mechanisms?

  • Central?

  • ability to rapidly modulate MU behavior?

  • slowing of voluntary contraction/relaxation speeds?

  • coordination of agonists & antagonists?

  • Peripheral?

  • slowed contractile properties at baseline

  • no effect of age on degree of (additional) slowing during fatigue

  • Distinguish central and peripheral by comparing slowing of voluntary contractions to slowing of stimulated contractions during fatigue


  • Login