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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
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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!!
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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
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