Physical exercise, especially resistance training, and nutritional supplementation can help prevent sarcopenia, the age-related loss of muscle mass and strength. Resistance training is most effective when performed 2-3 times per week for 8-12 repetitions at moderate to high intensity. Protein intake above the recommended daily amount, especially around exercise, may further boost the benefits. Hormonal therapies and drugs also show promise but require more research due to potential safety concerns. Lifestyle changes alone may not be sufficient, so alternative preventive strategies are still needed.

1. Dept. of Internal Medicine I University of Regensburg Dept. of Internal Medicine 2 Klinikum Nürnberg Germany Is Physical Exercise Sufficient To Prevent Sarcopenia? Which Way of Life for a Future Centenarian? 4 th International Seminar on Preventive Geriatrics 1 st International Seminar on Geriatric Rehabilitation Athens, 2 nd April 2011 Cornelius Bollheimer K LINIKUM N ÜRNBERG

2. 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%

3. Muscle Mass Is Not Everything In Sarcopenia 75 80 85 90 age 70 The C oncord H ealth and A geing in M en P roject = 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

4. 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 variables of sarcopenia primary secondary tertiary gait velocity

5. Preventive Options For Sarcopenia Burton & Sumukadas [2010] Clin Interv Aging // Rolland & Pillard [2009] J Nutr Health Aging Exercise Nutrition Hormones / Drugs Strength / Power Endurance Physical activity High quality proteins Creatine β -hydroxy-methylbutyrate » Exercise pill « Growth Hormone ACE-Inhibitors Testosterone 1. 2. 3.

6. power resistance strength resistance Hughes et al [2004] Am J Clin Nutr Raguso et al [2006] Clin Nutr Park et al [2010] Eur J Appl Physiol Coggan et al [1992] J Appl Physiol Charifi et al [2003] Muscle & Nerve Strasser et al [2009] Wien Klin Wochenschr muscle mass physical performance muscle strength muscle mass Liu & Latham [2010] Cochrane Database Syst Rev Peterson 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 muscle mass Physical Activity And Exercise: Which One Works ? aerobic endurance training resistance training increased physical activity ?

7. 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) t concentric = t eccentric 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) t concentric >> t eccentric no huge difference

8. In Principle, Resistance Training Works, But … Effectiveness ? muscle strength muscle mass 85% 95% 100% 77 65 12 years ageing 12 weeks strength resistance Roubenoff [2000] Eur J Clin Nutr / Frontera et al [2000] J Appl Physiol age Sustainability ?? Motivation ???

9. 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 15 10 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 and nutritional suppl. neither training nor nutritonal suppl. nutritonal suppl. only training only n= 63 n = 37 + 72-98 yrs  87 yrs physical performance muscle strength muscle mass cross sectional area [thigh] hip / knee extensors gait velocity * * * * ? ?

10. Stimulus for protein 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 Refining The Nutritional Approach - Perspectives Resistance training 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] Optimal prevention of sarcopenia ?

11. Hormones And » Exercise Pills « Against Sarcopenia ACEIs GH / IGF-1 Myostatin PKB / Akt mTor FOXO Proliferation Differentiation synthesis degradation AMPK Myostatin-Inhibitors Testosterone / 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

12. Intervention testosterone 100 mg transdermal gel Endpoints Placebo The T estosterone in O lder M en with Mobility Limitations Trial = TOM Basaria et al [2010] NEJM  200 ≥ 65 yrs [  74 yrs ] with limitations in mobility such 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

13. The T estosterone in O lder M en 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 Testosterone Placebo Leg-press strength [Newton] [percent of the group] 78 100 Testosterone Placebo 95 NNH ≈6 Subjects with one or more cardiovascular-related events in the testosterone group Subjects with one or more cardiovascular-related events in the placebo group Subjects without cardiovascular-related events during study period Benefit Drawback !

14. 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. 1 2 3 4