Bollheimer

MEDIZIN I UNIVERSITÄT REGENSBURG

Dept. of Internal Medicine I University of Regensburg

Dept. of Internal Medicine 2Klinikum Nürnberg

Germany

Is Physical Exercise Sufficient

To Prevent Sarcopenia?

Which Way of Life for a Future Centenarian?

4th International Seminar on Preventive Geriatrics1st International Seminar on Geriatric Rehabilitation

Athens, 2 nd April 2011

Cornelius Bollheimer

KLINIKUM NÜRNBERG


Everybody Loses Muscle Mass With Age

20 30 40 50 60 70 80

peak muscle mass

age

»Sarcopenia«

90

- 2SD

10

Janssen & Ross et al [2005] J Nutr Health Aging / Baumgartner et al [1998] Am J Epidemiol

15%>50%


Muscle Mass Is Not Everything In Sarcopenia

75 80 85 90 age70

The Concord Health and Ageing in Men Project = CHAMP Hairi et al [2010] JAGS // Waters et al [2010] Clin Interv Aging

muscle mass

grip strength

Critical hand grip for

sarcopenia

100 % -

50 % -

Δ 1-2% per yr

Δ 3% per yr


Prevention Of Sarcopenia Means A Lot

age

Cruz-Jentoft et al [2010] Age Ageing

muscle mass

muscle strength

physical performance

hand grip

muscle mass index

cut-off variablesof sarcopenia

primary

secondary

tertiary

gait velocity


Preventive Options For Sarcopenia

Burton & Sumukadas [2010] Clin Interv Aging // Rolland & Pillard [2009] J Nutr Health Aging

Exercise

Nutrition

Hormones / Drugs

Strength / Power EndurancePhysical activity

High quality proteinsCreatineβ-hydroxy-methylbutyrate

» Exercise pill «Growth HormoneACE-InhibitorsTestosterone

1.2. 3.


aerobic endurance training

resistance training

power resistance

strength resistance

Hughes et al [2004] Am J Clin NutrRaguso et al [2006] Clin Nutr Park et al [2010] Eur J Appl Physiol

Coggan et al [1992] J Appl PhysiolCharifi et al [2003] Muscle & NerveStrasser et al [2009] Wien Klin Wochenschr

muscle mass

physical performance

muscle strength

muscle mass

Liu & Latham [2010] Cochrane Database Syst RevPeterson et al [2010] Med Sci Sports Exerc Peterson et al [2011] Ageing Res Rev

Exercise = Planned, structured and repetitive bodily movement to improve or maintain one or more components of physical fitness

increased physical activity

muscle mass?

Physical Activity And Exercise: Which One Works ?


Resistance Training: Power Or Strength ?

General setting in the most studies:

training period: 2 - 6 months

training sessions: 2 - 3 days per week

each session: 3 - 4 sets per muscle group [e.g. leg extension and flexion]

each set: 8 - 12 repetitions

progressive adjustment of the load during the training period

Strength resistance

high intensity (70 - 80% RM) tconcentric = teccentric

Fielding et al [2002] JAGS // Miszko et al [2003] J Gerontol // Bottaro et al [2007] Eur J Appl Physiol // Henwood et al [2008] J Gerontol // Reid KF et al [2008] Aging Clin Exp Res // Bean et al [2009] J Gerontol // Marsh et al [2009] J Aging Phys Act

Power resistance

low intensity (30 - 60% RM) tconcentric >> teccentric

no huge difference


In Principle, Resistance Training Works, But …

Effectiveness ?

muscle strength

muscle mass

85%

95%

100%

7765

12 years ageing 12 weeks strength resistance

Roubenoff [2000] Eur J Clin Nutr / Frontera et al [2000] J Appl Physiol age

Sustainability ??

Motivation ???


Nutritional Supplementation To Prevent Sarcopenia ?

[% change from baseline] [% change from baseline]

-6

-4

-2

2

4

6

[% change from baseline]

125

100

50

75

25

-25

20

1510

5

-5

-10

Fiatarone et al [1994] NEJM

Lower body resistance training

10 wks // 3 d/wk // 3 sets // 8 repetitions

80% of maximal strength [progressive]

Nutritional supplementation

+ 369 kcal / d

17 Energy % Protein

training andnutritional suppl.

neither trainingnor nutritonal suppl.

nutritonalsuppl. only

trainingonly

n= 63

n = 37+ 72-98 yrs

87 yrs

physical performancemuscle strengthmuscle mass

cross sectional area [thigh] hip / knee extensors gait velocity

** *

*? ?


Stimulus forprotein biosynthesis

Nissen&Shrap [2003] J Appl Physiol // Morais et al [2006] J Nutr Health Aging // Campbell&Leidy [2007] J Am Coll Nutr // Candow et al [2007] J Nutr Health Aging // Morley [2008]JNHA // Paddon -Jones & Rasmussen [2008] Curr Opin Clin Nutr Metab Care // Gaffney-Stomberg et al [2009] JAGS // Rolland&Pillard [2009] J Nutr Health Aging // Tang&Philips [2009] Curr Opin Clin Nutr Metab Care // Burton&Sumukadas [2010] Clin Interv Aging // Kim et al [2010] J Nutr Chem // Waters et al [2010] Clin Interv Aging // Waters et al [2010] Clin Interv Aging

Protein ingestion > RDA of 0.8 g/kg [e.g. 1.2 g/kg]

Servings of 25-30 g high quality protein at each meal [e.g. lean meat]

Leucine Trigger [e.g. in legumes, beef, fish]

Clockwise supplementation of EAA immediately after training [e.g. 15 g within 1 hr]

Special supplements [e.g. 5g/d Creatine, 3g/d β-hydroxy-β-methylbutyrate]

Refining The Nutritional Approach - Perspectives

Resistance training

Optimal prevention of sarcopenia ?


Hormones And »Exercise Pills« Against Sarcopenia

ACEIs

GH / IGF-1

Myostatin

PKB / Akt

mTor FOXO

Proliferation

Differentiationsynthesis degradation

AMPK

Myostatin-InhibitorsTestosterone / SARMs

Cadilla & Turnbull [2006] Curr Top Med Chem // Tsuchida [2008] Curr Opin Drug Discov Devel // Witham et al [2008] Age Aging // Sakuma & Yamaguchi [2010] Curr Aging Sci

muscle protein satellite cells


Intervention testosterone100 mg

transdermal gel

Endpoints

Placebo

The Testosterone in Older Men with Mobility Limitations Trial = TOM Basaria et al [2010] NEJM

200 ≥ 65 yrs [ 74 yrs ]

with limitations in mobilitysuch as SPPB score 4-9 [ ≈ 7]

Total serum testosterone < 12 nmol/l [ ≈ 8,5 nmol /l]Free serum testosteorne < 170 pmol/l [ ≈ 155 pmol /l]

24 weeks

Starting Point

Primary: change in muscle strength [leg-press exercise]

Secondary [among others]: 50-m walking speed, stair-climbing speed

Testosterone Against Sarcopenia


The Testosterone in Older Men with Mobility Limitations Trial = TOM Basaria et al [2010] NEJM

The Anti-Sarcopenic Effect Of Testosterone:The Price Might Be Too High …

[ Study discontinuated]

1,0

1,6

1,7

Testosterone Placebo

50-meter walking speed [m/sec]

1000

1950

2150


Leg-press strength [Newton]

[percent of the group]

78

100


95 NNH≈6

Subjects with one or morecardiovascular-related events

in the testosterone group

Subjects with one or morecardiovascular-related events

in the placebo group

Subjects withoutcardiovascular-related events

during study period

Benefit

Drawback!


Conclusions

Sarcopenia (mass / strength / performance ) is a relevant geriatric syndrome which requires preventive strategies.

Resistance training - either in terms of strength or power training - might delay sarcopenia and rebuild muscle mass and muscle strength.

Supportive nutritional interventions have the potential to improve the anti-sarcopenic effects of resistance training.

Since the acceptance of life-style-modifiations will not be high, alternative approaches are needed to effectively prevent sarcopenia.

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Health & Medicine

Bollheimer