11

Dairy protein and muscle Dairy protein and muscle strength; strength;

Implications for fall prevention.Implications for fall prevention.

Dr David CameronDr David Cameron--SmithSmith

Senior LecturerSenior LecturerSchool of Exercise and Nutrition SciencesSchool of Exercise and Nutrition Sciences

Deakin UniversityDeakin University

22

33 44

Influence of age on muscle massInfluence of age on muscle mass

0

10

20

30

40

50

15 25 35 45 55 65 75 85

Age (years)

Mus

cle

Mas

s (k

g)

Men Women25 year old man

65 year old man

Janssen et al., J Appl Physiol 89:81-88, 2000

55

Longitudinal changes in muscle massLongitudinal changes in muscle mass

20253035404550556065

1982 1990

Qua

dric

eps

CSA

(cm

2 )

C.A. Grieg et al., Muscle & Nerve 1993;16:6-10

(x = 74 yr) (x = 82 yr)

66

Association between severe Association between severe sarcopeniasarcopeniaand physical function in older womenand physical function in older women

0 1 2 3 4 5 6 7 8 9 10 11

Performing Chores

Preparing Meals

Personal Care Needs

5 Chair Stands

Walk 8 Feet

Lift 10 lbs

Climb 10 Stairs

Walk 1/4 Mile

Adjusted Odds Ratio (95% CI)(Normal Muscle used as Referent Group)

Janssen et al., J Am Geriatr Soc 50:889-896, 2002

77

Vicious Cycle of Vicious Cycle of SarcopeniaSarcopenia

88

No loss of fibre strength with ageNo loss of fibre strength with age

00.20.40.60.8

11.2

Type 1 Type 2

YMYW

OMOW

Trappe S et al J. Physiol. 552: 47-58, 2003.

*

*

99

Muscle plasticityMuscle plasticity

1010

Skeletal MuscleSkeletal Muscle

1111

Multinucleated Multinucleated myofibresmyofibres

Newlands S. et al. Genes & Development 12: 2748-2758, 1998 1212

Hawke & Garry J App Physiol. 91: 534-551, 2001.

1313

Muscle recovery following Muscle recovery following cardiotoxincardiotoxinexposureexposure

Garry DJ et al PNAS 97: 5416-21, 20001414

Zoico et al (2002). Nutrition Reviews 60: 39-51

1515

The Interplay Between Chronic The Interplay Between Chronic Inflammation & Acute Phase ResponseInflammation & Acute Phase Response

As yet there is no As yet there is no data that data that demonstrates demonstrates whether whether supplemental supplemental protein ingestion, protein ingestion, following following eccentric exercise eccentric exercise is able to is able to favourably impact favourably impact on the chronic and on the chronic and acuteacute--phase phase 1616

*

#

^

* denotes a significant difference (P<0.05) in the Placebo group between the pre and 2hr time point. ̂denotes a significant difference (P<0.05) between the Placebo and BLG group at the 2hr time point.

# denotes a significant difference (P<0.05) in the BLG group between the pre and 2hr time potnt.

c-fos

Pre 2 h 4 h 24 h0.000

0.025

0.050

0.075

0.100PlaceboBLG

Gen

e ex

pres

sion

norm

alis

ed to

GA

PDH

Muscle Inflammation & Dairy ProteinMuscle Inflammation & Dairy Proteincc--fosfos

Whey

Mathers et al, Unpublished

1717

Myogenic Regulatory Factors (Myogenic Regulatory Factors (MRFsMRFs) & ) & Growth Factors Growth Factors

Charge & Rudnicki. Physiol. Rev. 84: 209-38, 2004.1818

Myogenic Regulatory Factors (Myogenic Regulatory Factors (MRFsMRFs) & ) & Growth Factors Growth Factors

Charge & Rudnicki. Physiol. Rev. 84: 209-38, 2004.

1919

Myogenic Factors and Dairy ProteinMyogenic Factors and Dairy ProteinMyoD

00.05

0.10.15

0.20.25

0.30.35

0.40.45

0.5

pre 2 h 4 h 24 h

PlaceboBLG

Myogenin

00.2

0.40.60.8

11.2

1.41.6

Pre 2 h 4 h 24 h

PlaceboBLGMyo D MyogeninPlacebo

Whey

Carey et al, Unpublished data 2020

Growth Factor Signalling PathwaysGrowth Factor Signalling Pathways

Glass D. Nature Cell Biology 5: 87 - 90, 2003.

2121 2222

Muscle BiopsiesMuscle Biopsies

2323

1. Reductions in satellite cell number1. Reductions in satellite cell number

Kadi et al, Muscle & Nerve 29: 120-27, 2004 2424

2. Reduced Proliferative Potential2. Reduced Proliferative Potential

Bortoli et al Gene 321; 145-154, 2003.

2525

Acute Acute MyoDMyoD Response in Older Response in Older HumansHumans

Hameed et al. J. Physiol. 547: 247-54, 2002.2626

Genetic basis of impaired proliferation is Genetic basis of impaired proliferation is poorly understoodpoorly understood

Bortoli et al. Gene 321; 145-154, 2003.

2727

Protein Synthesis Protein Synthesis –– PostPost--ExerciseExercise

Sheffield-Moore et al. Am. J. Physiol. Endo. Metab. 287:E513-E522, 2004 2828

Protein Breakdown Protein Breakdown –– PostPost--ExerciseExercise

Sheffield-Moore et al. Am. J. Physiol. Endo. Metab. 287:E513-E522, 2004

2929

Muscle Atrophy Gene Muscle Atrophy Gene -- MyostatinMyostatin

Shuelke et al. New Eng J. Med. 350; 2682-88, 20043030

MyostatinMyostatin FunctionFunction

McNally New Eng J Med 350: 2642-43, 2004

3131

MyostatinMyostatin mRNA response to resistance mRNA response to resistance exerciseexercise

Myostatin

pre 30min 4h 24h0.000

0.005

0.010

0.015

0.020

0.025

** **

mR

NA

expr

essi

on re

lativ

e to

b-ac

tin

Carey et al, Unpublished data3232

AtrogenicAtrogenic PathwayPathway

3333

AtroginAtrogin--1 and MURF1 and MURF--11

Atrogin-1

pre 30min 4h 24h0.000.050.100.150.200.250.300.350.400.450.500.55

mR

NA

expr

essi

on re

lativ

e to

b-ac

tin

MURF-1

pre 30min 4h 24h0.000

0.001

0.002

0.003

0.004

0.005

mR

NA

expr

essi

on re

lativ

e to

b-ac

tin

3434

Strength Gains in 12 WeeksStrength Gains in 12 Weeks

Farnfield et al, Unpublished Data

0

5

10

15

20

25

30

35

40

45

50

Older Adult Younger Adult

Incr

ease

in P

eak

Torq

ue S

tren

gth

(%) Concentric

Eccentric

3535

Exercise training in the very old: 85+yrsExercise training in the very old: 85+yrs

Fiatrone MA et al New Eng. J. Med. 330: 1769-75, 1994 3636

Resistance Exercise Protein

S6K1 S6K1 - P4E-BP1 4E-BP1-P

Protein synthesis

+ +

activation

CSAMHC

CrossCross--over between exercise and over between exercise and protein availabilityprotein availability

Leucine

3737

Leucine ComparisonsLeucine Comparisons

Protein SourceProtein Source Leucine (mg/g protein)Leucine (mg/g protein)bb--LactoglobulinLactoglobulin 136136lactalbuminlactalbumin 104104BSABSA 104104ImmunoglobulinsImmunoglobulins 9696GMPGMP 170170LactoferrinLactoferrin 106106CaseinCasein 9595

Harper WJ, 2000 3838

Fast versus slowFast versus slow

0

20

40

60

80

100

120

0 40 80 120 160Time (min)

nitr

ogen

(mm

oles

)

whey proteincasein

3939

Older males Older males –– Impact of TimingImpact of Timing

Immediate

2hours after

Esmark et al. J. Physiol. 535: 301-311, 2001 4040

Changes in Muscle CharacteristicsChanges in Muscle Characteristics

Esmark et al. J. Physiol. 535: 301-311, 2001

4141

In young males?In young males?

Burke et al. Int. J. Sport Nutr. Exerc. Metab. 11: 349-64, 2001 4242

In bodybuilders…In bodybuilders…The effect of VP2 whey isolate, The effect of VP2 whey isolate, micronizedmicronized creatine and resistance creatine and resistance

training on fibre characteristics, strength and body compositiontraining on fibre characteristics, strength and body composition11 week intervention in resistance-trained men.

Strength gains (1RM max)Creatine/carbohydate 284%Whey isolate 308%Creatine/Whey isolate 371%

versus placebo

Type 2 muscle fibre areaCreatine/carbohydate 793%

Whey isolate 543%Creatine/Whey isolate 1230%

versus placebo

Cribb et al 2003 Experimental Biology meeting

4343

THAT’S IT FOLKS!!THAT’S IT FOLKS!!

4444

SizeStrength

CSAStructural proteins

Translation initiationSignalling protein activationGrowth factor activationMyogenic/Atrogenic Genes

AA blood responseAA composition

Clinical evidence

Pre-clinical evidence

Fundamental & mechanisticevidence

Nutritional Basis

Exercise Stimulus

DairyProtein

Young& Old

4545

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