Anti-aging process

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