Robin M. Daly PhD, FASMF

Robin M. Daly PhD, FASMF Professor Chair of Exercise and Ageing Centre for Physical Activity and Nutrition Research (C-PAN) Deakin University, Burwood, Melbourne Email: rmdaly@deakin.edu.au

The average adult loses 250 g of muscle every year between the ages of 30 and 60 years. Muscle Mass Muscle Strength Men kg Nm Age Lose 25-40% from the age of 20 to 60 to 90 yrs Women Age Lose 45-60% from the age of 20 to 70-90 years Janssen et al. J Appl Physiol 2000 Lindle et al. J Appl Physiol 1997

Three-year changes in 1880 adults aged 70-79 years in the Health ABC Study Rates of loss in leg muscle strength about 3-fold greater than leg lean mass Muscle strength Lean mass Goodpaster BH et al. J Gerontol A Biol Sci Med Sci 2006

Low Muscle Strength RR = 2.20 (95% CI: 1.5-3.1) Risk of Poor Physical Performance or Disability in Adults with Low Muscle Strength or Muscle Mass Relative risk (RR) of poor physical performance, functional limitation or physical disability Low Muscle Mass RR = 1.37 (95% CI: 0.9-2.0) 2.2-fold for low muscle strength 1.4-fold for low muscle mass Manini TM and Clark DC. J Gerontol A Biol Sci Med Sci 2011

Change (% per year) 10-Year Prospective Population Based Study Males 0.5 Grip Strength Females Males 1 Balance Females Males 2 Gait Velocity Females -0.5 0 1-1.5-2.5-1 -2 0-1 -2-3.5-4.5-3 -4 p<0.001 p<0.001-3 -4 p<0.01 - <0.001 Age change categories (years) Mean changes (95% CI) All analyses were performed adjusting for: height, rural/urban living, change in self reported disability, change in disease/medication use, change in habitual physical activity, menopause status, smoking history, and baseline values for the respective measurements Daly R et al. unpublished

2010 European Consensus on Definition and Diagnosis European Consensus Definition Sarcopenia is a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death. Diagnosis based on documentation of criterion 1 plus (criterion 2 or 3): Low muscle mass + Low muscle strength OR + Low physical performance Cruz-Jentoft et al. Age Ageing 39;412-23, 2010

Relative Skeletal Muscle Index (RSMI) RSMI (or SMM) = Appendicular skeletal muscle mass (ASM) / height (m) 2 [sum the muscle mass (lean mass) of the four limbs] Less than 2 SD below the sex-specific mean of a healthy young person (reference 18-40 years of age) Female: < 5.45 kg/m 2 Males: < 7.26 kg/m 2 Baumgartner et al., Am J Epidemiol 1998;147:755-763

Slide Adapted from Cruz-Jentoft AJ. American Geriatric Society Annual Meeting, 2011 Cruz-Jentoft et al. Age Ageing 39;412-23, 2010

<0.8 m/s >0.8 m/s Slide from Cruz-Jentoft AJ. American Geriatric Society Annual Meeting, 2011

Muscle Power (Force x Velocity) = Ability to Produce Force Rapidly Muscle Power Chair-rising Power Type II Type I Lose up to 70-75% from the age of 20 to 70+ years. Preferential loss and atrophy of type II fast twitch muscle fibres. Runge et al. Clin Physiol Funct Imaging 24(6): 335 340.

Categories of Sarcopenia by Cause Cruz-Jentoft et al. Age Ageing 2010; 39:412-23; Cruz-Jentoft A. American Geriatric Society Annual Meeting, 2011 Fielding R et al. J Am Med Dir Assoc 2011; 12:249-56.

2007 Recommendations for Adults >65 years with chronic conditions Aerobic Exercise 30 minutes of moderate intensity on 5 days/week * OR 20 minutes of vigorous intensity on 3 days/week. and Resistance Exercise 8-10 exercises @ 10-15 repetitions performed on 2 nonconsecutive days; progressive; moderate (5-6) to vigorous (7-8) on the Borg Scale of 0 to 10. and if at risk of falling Balance Exercise Progressively challenging exercises to help maintain balance and prevent falls; no current recommendations on the dose. * You can bank aerobic activity throughout the day. However, activities must last for at least 10 min without stopping to count toward your daily total (eg. 3 x 10 min bouts = 30 minutes). Nelson M et al. Med Sci Sports Exer 39: 1435-45, 2007

Meta-analysis of RCTs and non RCTs in Adults Aged 50 years Changes in Lean Body Mass (LBM) Mean 1.1 kg Lean body mass increased by an average 1.1 kg [95% CI 0.9 to 1.2 kg, P<0.001] Strong linear association between the volume of training and the magnitude of the change in LBM. Muscle strength increases ranged from 9.8 to 31.6 kg, and percentage changes were 24% to 33% for legs, chest press and back. Peterson et al. Med Sci Sports Exer 2011; Peterson et al Ageing Res Rev 2010

Review of RCTs of PRT with any balance outcome in adults aged >50 years (mean 60 years) 29 eligible studies reviewed 68 balance tests 15 of 68 tests (22%) showed significantly improved balance performance following PRT. Orr et al. Sports Med 38(4):317-43, 2008

Effects on Muscle Function / Performance Twenty-nine trials with a total of 1313 subjects (mean age 65-81) Power Training vs. Traditional PRT Steib et al. Med Sci Sports Exer 2010 May;42(5):902-14.

Exercise Reduced Falls by 17% - What is Optimal? = 2 x week for 25 weeks Sherrington et al. J Am Geriatr Soc 2008; 56:2234-43.

The results based on 13 RCTs indicated that Tai Chi was effective in improving balance of older adults but may not necessarily be superior to other interventions (Leung et al. Altern Ther Health Med. 2011;17(1):40-8). The effects of Tai Chi on falls is equivocal (Harmer PA, Li F. Med Sport Sci. 2008;52:124-34) Tai chi is effective at improving balance confidence (Rand et al Age Ageing 2011) Rand et al. Age Ageing 2011; 40: 297 306139-46

Systemic review: WBV improve muscle strength, power and balance in older people compared with a control group, but was not more effective than conventional exercise (Sitjà-Rabert et al. Disability & Rehabilitation 2012). Vertical-oscillating Platform Side-alternating Platform Can produce forces ranging from 0.1 to 10 G

Best Practice Recommendations To prevent sarcopenia: prescribe moderate to high intensity progressive resistance training. Mixed results on the effect of PRT on measures of muscle function To optimise muscle function: prescribe high challenging balance and power training (high velocity PRT). Focus on muscle force and movement speed. For falls prevention: moderate to high challenging balance activities (> 50 hours of training) + lower extremity strengthening exercise (add dual task activities).

Marked Heterogeneity in the Anabolic Responses to Resistance Training 67 years 79 years Muscle CSA -2% 59% Muscle Strength 0% 250% Hubal et al. Med Sci Sports Ex 2005 Peterson et al. Med Sci Sports Exer 2011; Peterson et al Ageing Res Rev 2010

High = two of more inflammatory markers in the highest tertile at baseline, Mid = one marker in the highest tertile at baseline, Low = no marker in the highest tertile at baseline. Peake et al. Eur J Appl Physiol 2011

Categories of Sarcopenia by Cause Nutrition Information Protein Protein requirements Quantity of protein Quality / type of protein Vitamin D Optimal serum 25(OH)D? Muscle, function & falls Optimal dose? Exercise + Nutrition Interaction Energy-protein + resistance training Vitamin D-calcium + resistance training Cruz-Jentoft et al. Age Ageing 2010; 39:412-23; Cruz-Jentoft A. American Geriatric Society Annual Meeting, 2011

Blunted Response to Exercise / Protein Ingestion Difference in MPS between elderly and young MPB MPB MPB MPB Breen and Phillips. Nutrition and Metabolism 2011:8:68

Inadequate dietary protein and a blunted anabolic response to protein have been linked to sarcopenia; coined anabolic resistance. RDI s for older adults of ideal weight: Women: 0.75 to 0.94 g/kg (46 to 57 g/d) Men: 0.84 to 1.07 g/kg (64 to 81 g/d) Some suggest that older adults (esp. active adults) may require 1.0 to 1.5 g/kg to prevent muscle loss. For a 65 kg women = about 65 to 95 g/d

Exercise-induced gain in muscle mass (kg) Protein Sources: Milk Whey Casein Soy? Rankin et al. J Am Coll Nutr 2004 Hartman et al. Am J Clin Nutr 2007 Crib et al. Int J Sports Nutr Ex Metab 2006 Crib et al. Med Sci Sports Ex 2007 Candow et al. Int J Sports Nutr Ex Metab 2006 Adapted from Tang and Phillips Curr Opin Clin Nutr Metab Care 2009; 12:66-71

Effect of Timing of Protein Intake Quadriceps Muscle CSA Early provision of protein immediately post-exercise appears to be most effective to augment protein synthesis and enhance lean mass gains in response to resistance training. Protein immediately post exercise Protein 2-hours post exercise These findings are not universal; some evidence in young adults that muscles remain sensitive to protein ingestion at 24 h post exercise (Burd et al. J Nutr 2011;141:568-73) Esmarck et al. J Appl Physiol 2001

Effect of Dose of Protein Intake The elderly are less responsive to EAA and so require a higher dose to elicit the same stimulatory response. Maximal stimulation of muscle protein synthesis is achieved with 10-15 g of EAA [equivalent to 20-30 g of high quality protein = 120 g of lean red meat]. Ingestion of a large single dose (90 g of protein) does not elicit a greater anabolic response than a serve 1/3 the size; 30 g per serve appears optimal. Symons et al. J Am Diet Assoc 2009;109:1582-86. Muscle Protein Synthesis Elderly Young Breen and Phillips. Nutrition and Metabolism 2011:8:68 Young Elderly

A major source of high-quality protein, providing all the essential amino acids. Just 100 g of raw red meat contains around 20 to 25 g of protein. The protein in beef and lamb is highly digestible Around 94% compared with the digestibility of 78% in beans and 86% in whole wheat. Trimmed of fat, lean red meat contains low levels of saturated fat, cholesterol and sodium and is high in potassium. Essential amino acids Isoleucine Leucine Valine Lysine Methionine Phenylalanine Threonine Tryptophan

Exercise Program Progressive resistance training (twice a week); 3 sets of 8-12 reps; 15-16 (hard-very hard) on RPE scale; DBs, ankle weights, Swiss balls etc. Small group sessions (6-8 women per group); 45 to 60 minutes per session. 1. High Protein - Lean Red Meat Supplied with 220 g (raw weight) of lean red meat (beef, lamb, veal) (160 g of cooked meat) per day for 6 days per week (protein intake 1.3 g/kg/d) 2. Carbohydrate (Control) Group Instructed to consume a diet containing a protein intake of 0.75 g/kg/d.

Change relative to baseline (%) 2.5 2.0 1.5 1.0 0.5 Total Body Lean Mass p<0.05 *** Total body Lean Mass Lean red meat +0.6 kg Carbohydrate +0.1 kg 0.0-0.5-1.0 RT+CHO RT+Meat *** p<0.001 vs baseline Change relative to baseline (%) 7.0 6.0 5.0 4.0 3.0 Distal Femur Muscle CSA *** *** Both groups experienced a similar significant increase in leg muscle cross-sectional area after 4 months training 2.0 Muscle 1.0 0.0 RT+CHO RT+Meat *** p<0.001 vs baseline *** p<0.001 vs baseline Daly R et al. unpublished

% Change Baseline % Change Baseline 60 50 40 30 20 Leg Muscle Strength ** P<0.05 *** Leg extension strength Lean red meat 40% Carbohydrate 19% 10 0 RT+CHO RT+Meat ** p<0.01, *** p<0.001 vs baseline 100 80 60 40 Leg Muscle Power Leg Muscle Power ** *** Both groups experienced a similar and significant increase in leg muscle power 20 0 RT+CHO RT+Meat ** p<0.01, *** p<0.001 vs baseline Daly R et al. unpublished

50 40 *** 30 s Sit-to-Stand Test Change relative to baseline (%) 30 20 *** Change relative to baseline (%) 10 0 12 9 6 3 *** *** *** p<0.001 vs baseline Timed-up-and go Test 0 *** p<0.001 vs baseline 20 15 ** ** Four-square test Change relative to baseline (%) 10 5 0 RT+CHO RT+Meat ** p<0.01 vs baseline Daly R et al. unpublished

Percent of population Lower serum 25(OH)D levels are associated with greater losses in muscle strength, muscle mass and function in older persons. 35 30 25 3-year Follow-up P=0.001 <25 nmol/l 25-50 nmol/l 50+ nmol/l NHANES III 4100 ambulatory adults aged 60+ years 20 15 P=0.09 10 5 0 Loss of Grip Strength (>40%) Loss of Appendicular Skeletal MM (>3%) Visser et al. J Clin Endocrinol Metab 88:5766-72, 2003 Bischoff-Ferrari et al. Am J Clin Nutr 2004; Dawson-Hughes et al. Osteo Int 2005

Proximal muscle weakness is a prominent feature of the clinical syndrome of vitamin D deficiency. (Glerup et al. Calcif Tissue Int 2000) Specific receptors for vitamin D (VDR) are expressed in human muscle tissue, and their number decline with age. (Bischoff-Ferrari et al. J Bone Miner Res 2004) Bischoff-Ferrari et al. J Bone Miner Res 2004 In a 2-year RCT, treatment with ergocalciferol (1000 IU per day) increased the diameter and relative number of type II muscle fibers in the functional limbs of 48 severely vitamin D deficient, elderly stroke patients. Sato Y et al. Cerbrovasc Dis 20:187-92, 2005.

Vitamin D status assess via serum 25-hydroxyvitamin D Severe deficiency: <12.5 nmol/l 5 ng/ml Moderate deficiency: 12.5 to <25 nmol/l 10 ng/ml Mild insufficiency: 25 to <50 nmol/l 20 ng/ml Sufficiency Insufficiency: 50 50 to nmol/l <75 nmol/l? >20 <30 ng/ml New sufficiency 75 nmol/l? 30 ng/ml The half-life of circulating 25(OH)D is reported to be about 3 weeks. 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate

Prevalence (%) Prevalence of Suboptimal Vitamin D by Age and Gender 100 90 80 70 60 50 40 30 20 10 0 Males 41.0 34.5 29.2 27.6 31.7 43.5 47.5 44.0 46.3 42.4 16.6 21.5 23.3 28.9 22.0 26.3 46.1 27.6 100 90 80 70 60 50 40 30 20 10 0 35.3 38.6 26.1 24.3 39.7 36.0 Females 18.8 14.5 11.8 9.4 34.0 37.7 41.8 42.2 43.5 43.7 46.0 56.6 25-34 y 35-44 y 45-54 y 55-64 y 65-74 y 75+ y 25-34 y 35-44 y 45-54 y 55-64 y 65-74 y 75+ y Age Categories Age Categories <50 nmol/l 50 to <75 nmol/l 75 nmol/l Serum 25-hydroxyvitamin D Daly R et al. Clin Endocrinol 2012

Effect of Vitamin D Dose and Serum 25(OH)D Levels on the Relative Risk of Falling Falls Prevention by Dose of Vitamin D Vitamin D 700-1000 IU Pooled RR 0.81 (95% CI 0.71-0.92) Falls Prevention by Serum 25(OH)D Level Serum 25OHD 60 nmol/l Pooled RR 0.77 (95% CI 0.65-0.90) Circles represent relative risks ( 95% CI) Bischoff-Ferrari et al. BMJ 2009;339;b3692

High intensity PRT (60-80% 1 RM) plus impact exercise, 3/week 2 x 200 ml tetra packs per day (Each tetra pack: 500 mg calcium; 400 IU vitamin D3; 418 kj energy, 6.6 g protein, 2.2 g fat, Kukuljan et al. J Apple Physiol 107:1864-73, 2009 Change from baseline (%) Change from baseline (%) 50 40 30 20 10 0-10 -20 3.0 2.0 1.0 0.0-1.0-2.0-3.0 Mid Femur Muscle CSA Cont (n=44) Muscle Strength Milk (n=45) Ex (n=46) Ex+Milk (n=45) Data represents mean changes (SE)

24 week Randomised Controlled Trial Postmenopausal Women 5000 Muscle CSA Quadriceps Strength Area (mm 2 ) 4800 4600 4400 4.3% * * 6.0% 14% 8% 4200 4000 Baseline 12 wk Baseline 12 wk Control (n=13) Nutrient (n=16) Nutrient Supplement: 730 kj, 10g protein (whey), 31g CHO, 400 IU vitamin D and 250mg calcium (supplement ingested immediately after each training session). Exercise Program: Resistance training program (2-3 times per week lower extremities) Holm L et al. J Apple Physiol 105: 274-81, 2008.

Best Practice Recommendations Additional protein can enhance the effects of resistance training on muscle mass and strength in older adults. Recommended dose: 1.3 g/kg/d? To maximise muscle protein synthesis and promote exerciseinduced gains in lean tissue mass, a meal that contains 20-30 g of high quality protein (10-15 g EAA) appears optimal. Leucine-enriched protein appears to be most effective for increasing muscle protein synthesis. Vitamin D in a dose of 700-1000 IU/d and achieving a serum 25(OH)D level of at least 60 to 75 nmol/l appears best to enhance lower extremity muscle function and prevent falls. Higher doses are required for those with severe vitamin D deficiency.