Lecture outline. Skeletal muscle as human engine. Humans are made to MOVE! BELANG VAN BEWEGEN BIJ OUDEREN De spier als motor van ons lichaam

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BELANG VAN BEWEGEN BIJ OUDEREN De spier als motor van ons lichaam Lex B. Verdijk Geriatric Giants, April 21, 2016 The aging human engine Lecture outline What regulates muscle maintenance? Exercise and nutrition for muscle maintenance in elderly Department of Human Biology and Movement Sciences Maastricht University Medical Centre, Netherlands Humans are made to MOVE! Skeletal muscle as human engine 50% of body weight Major factor in mobility / physical performance Major metabolic organ Highly adaptive tissue One engine to accompany all needs Healthy engine 1

Sports engine Frail / sarcopenic engine Muscle mass maintenance Sarcopenia Height and weight matched Young Male, age 25 Older Male, age 81 Short and Nair, 2000 Loss of muscle mass and strength Loss of muscle function Ferrucci et al., J. Gerontology, 2012 Lauretani, JAP, 2003 2

Muscle protein synthesis (%/h) Consequences of sarcopenia What regulates skeletal muscle mass - Muscle mass and function - Physical activity - ADL - Chronic metabolic disease - Disability and independence - Vicious downward spiral - Health care costs - Quality of life Muscle protein synthesis and breakdown Main anabolic stimuli 1-2 % per day synthesis breakdown (0.04 0.14 %. h -1 ) Food/protein intake Physical activity Post-prandial muscle protein synthesis Protein intake and muscle loss 0.10 0.08 Muscle protein synthesis rate +35% g/kg/d: 0.7 0.7 0.8 0.9 1.1 0.06 0.04 0.02 0.00 Basal AA infusion Bennett et al, Clin Sci,1989 Houston et al., AJCN 2008 3

Muscle protein synthesis (%/h) Delta ALM (kg) Post-exercise muscle protein synthesis Physical activity and muscle loss 0.12 0.10 0.08 0.06 0.04 0.02 0.00 Muscle protein synthesis rate +100% Control Exercise Appendicular lean mass loss over 5 years 0.00-0.10-0.20-0.30-0.40-0.50-0.60-0.70-0.80-0.90-1.00 Q1 Q2 Q3 Q4 Quartiles of physical activity level of men 65-84y Chesley et al, JAP1992 Shephard et al, JAGS 2013 Physical inactivity associated with: Loss of muscle mass and function Lower endurance / fatigue resistance Loss of coordination and balance Increased fall risk Use it or lose it Jack Lalanne at 21 Jack Lalanne: 70 years of exercise promotion!!! Cognition/dementia Obesity Diabetes CVD Jack Lalanne at 71 Jack Lalanne at 93 Catabolic crisis model Hospital admission Short periods of bedrest following disease or injury contribute substantially to the loss of muscle mass with aging English et al., Curr Opin Clin Nutr Metab Care, 2010 Wall et al., Aging Res. Rev., 2013 4

Injury and disease Short term muscle disuse atrophy Slides with preliminary data deleted Wall et al. Acta Physiol. Scand., 2013 Interventions to counteract sarcopenia M3 research group Nutrition???? Exercise???? - How fast are muscle proteins being build (muscle protein synthesis rates)? - Which interventions further stimulate this process? 5

Muscle protein synthesis (%/h) Intrinsically labelled milk protein Intrinsically labelled milk protein - How fast are muscle proteins being build? - How much of the protein we eat ends up in the muscle? van Loon et al., J Dairy Sci, 2009, Pennings et al., J Dairy Sci, 2010, Burd et al., Plos One, 2013 Milk-derived amino acids in muscle tissue Je bent wat je eet Groen et al., PLOS One 2016 Physical activity before protein intake Na inspanning Muscle protein synthesis rate +22% +28% More of the ingested protein ends up in the muscle Ben je nog meer wat je eet Pennings et al, AJCN 2010 6

Delta lean mass (kg) Maximum weight lifted Interventions to counteract sarcopenia 8 wk resistance training frail elderly > 90 y - 9% increase quadriceps size - 150% increase strength - 50% increase gait speed Baseline week 8 Fiatarone, JAMA, 1990, Additional benefit of milk protein at breakfast and lunch in frail elderly Some benefits of whey at breakfast and lunch in sarcopenic subjects 4-5% increase in protein group only Tieland et al, JAMDA 2012 Bauer et al, JAMDA 2015 Some benefits of milk protein at breakfast and lunch in healthy older subjects Oral nutritional supplement reduced mortality in malnourished elderly 0.5 0.4 0.3 0.2 0.1 0-0.1-0.2 Appendicular Lean Tissue Control Protein Norton et al, J Nutr 2015 Deutz et al, Clin Nutr, 2016 7

Conclusions Sarcopenia: loss of muscle mass and function with aging Important role for reduced physical activity and reduced food intake (primarily protein). Downward spiral of reduced activity leading to loss of muscle mass and increased disability, leading to furhter inactivity, etc. Also strong link with other age-related disease and multi-morbidity. Physical activity and protein intake stimulate muscle build-up / maintenance. Resistance training effectively increases muscle mass, strength, and function up to very high age Sufficien protein intake is essential to optimize benefits of training Specific protein supplementation can have additional benefits. Conclusions Muscle tissue remains responsive to anabolic effects of protein and exercise throughout life, but tailored approach is likely needed: Protein dose requirements for maintaining and increasing muscle mass and function are increased in elderly - Ingesting 1.2 1.5 g/kg body mass per day - Ingesting 25 30 g with each main meal - Ingesting high quality protein (EAA / leucine) - Ingesting protein close to physical activity and / or before sleep Protein supplementation can have isolated benefits for muscle mass and/or function Combining protein with exercise provides strongest stimulus for maintenance and even improvement of muscle mass and function. Daily practice??? Daily practice??? NMES in hospitalized patients? Daily practice??? Daily practice??? 8

Daily practice??? Belang van bewegen: USE IT OR LOSE IT Serra-Rexach, JAGS 2011; Clemson, BMJ 2012 Acknowledgements Sponsors and collaborators M3 research group Dr. Lex B. Verdijk Lex.verdijk@maastrichtuniversity.nl www.m3-research.nl 9