Muscle mass and strength

1. Muscle mass and strength • Muscle mass is the primary determinant of strength • Obese individuals have higher lean mass therefore are stronger than thinner people • Men have proportionally more lean than women thus are stronger at the same weight • Sarcopenia, the loss of muscle mass is the major determinant of the loss of strength with age.

2. Muscle strength across the lifespan

3. Strength declines across age groups 70-79 Health ABC Torque (Nm) Age

4. Changes in muscle with age • Loss of muscle fibers • Loss of motor neurons at the spinal cord level • Reduction in type II fibers from 60% to 30% • Increased infiltration of muscle with fat

5. Changes in muscle metabolism with age • Increase in mitochondrial DNA mutation • Decline in muscle mitochondrial protein synthesis (40%) • Decreased oxidative phosphorylation and ATP generation • Results in fatigability • Decline in myosin heavy chain synthesis • Major protein involved in ATP and conversion of chemical to mechanical energy

6. Sarcopenia: What is driving the process? • Chronic inflammation? • Acute inflammation: anorexic - catabolic state • Relationship to cancer and cardiac cachexia? • Decline in anabolic hormones? • GH/IGF-1 • Decline in sex steroid hormones • Free testosterone • DHEA • Fading effectiveness of insulin • Loss of innervation?

7. Muscle Quality – Loss of strength greater than loss in muscle mass (Health ABC) Nm of torqueper cm2 muscle area Age

8. Muscle quality Strength Function Lean mass/muscle + ? _ Fat mass

9. Skeletal Muscle fat Less More Most

10. Histochemical Staining of Neutral Fat Content within Skeletal Muscle Fibers

11. Muscle area and attenuation are both inversely associated with age: The Health ABC Study 50 Men 180 Women 160 45 140 40 Mid-thigh attenuation (HU) Mid-thigh CSA (cm2) 120 35 100 30 80 60 25 <71 71-72 73-74 75-76 77-78 79-80 <71 71-72 73-74 75-76 77-78 79-80 Age (y) Age (y) Goodpaster, BH. J Appl Physiol 2001;90:2157-2165.

12. Men Women What About the Quality of Muscle? 1.3 1.2 1.1 Specific force (Nm•cm-2) 1.0 0.9 0.8 0.7 < 30.9 31.0-35.5 35.6-40. > 40.4 Muscle Attenuation (HU)

13. “Metabolic Obesity”Intermuscular fat and Visceral fat:Associations with Fasting Insulin by BMI strata Women Men Standardizedbeta BMI BMI

14. Lower extremity function is worse with higher fat and lower muscle area – Health ABC * * * *P<0.01 * * Lower-extremity performance * Tertiles of total body fat Tertiles of mid-thigh muscle area Visser M, et al, JAGS, in press

15. What is the prevalence of sarcopenia? • No standardized definition to define an individual as sarcopenic • Several proposed methods • Lean mass • Lean mass relative to healthy young adult • Lean mass adjusted for height or height squared • Lean/fat ratio • Lean for fat mass and height

16. Prevalence of sarcopenia and sarcopenic obesity in Health ABC - lean mass adjusted for height and fat mass

17. Risk factors for Sarcopenia • Likely multifactorial and complex • Both behavioral and biological factors probably important • Few identified • New Mexico Elder Health Survey: • Age, income, low activity, smoking, lung disease (Baumgartner, 1998) • Higher SHBG ( Baumgartner, 2001) • Health ABC: • Age, physical activity, smoking; in men, cancer and number of chronic conditions

18. Prevention approaches • Maintain or increase lean mass • Avoid weight loss • Anabolic hormones (GH - IGF-1, Testosterone, DHEA’s) • Block cytokines (TNF alpha, Il-6?) • Nutritional approaches - ranging from creatine to caloric restriction • Maintain or increase muscle quality • Improve metabolic capacity of muscle • Decrease loss of type 2 fibers • Strength training

19. Clinical trials to prevent sarcopenia • Testosterone, DHEA • Both result in very small increases in lean mass and strength with side effects limiting use • GH, GH secretagogues • Slight increase in mass without increase in strength • Exercise • Minimal increase in mass, but large increase in strength

20. pre Extension post Flexion The role of exercise in the prevention of sarcopenia 50 150 45 40 140 35 30 130 Knee Strength (kg) 25 Area (cm2) 20 120 15 10 110 5 0 100 Right Left 0 12 Weeksof Resistance Training Frontera et al. J. Appl. Physiol., 1988

21. Lessons from observations of regarding sarcopenia and muscle quality • Preserving lean mass is likely the major key to preserving strength • The quality of the muscle is also important - fat infiltration impairs muscle quality • Both quantity and quality are important targets for the preservation of function in older age

22. Conclusions • Methodologic advances in the ability to quantify muscle mass and fat distribution have been key to progress • More work is now needed to determine risk factors • Preventive interventions will be depend in part on these findings • Current strategies • Avoid weight loss • Exercise

23. End • Anne B. Newman, MD, MPH • Sarcopenia in Older Adults • August 19th • University of Pittsburgh School of Medicine • Pittsburgh, PA, 15213 • 412-624-4012 • anewman@pitt.edu