1. The Challenge of Understanding Sarcopenia, Muscle Strength and Disability Jack M. Guralnik, M.D., Ph.D. Department of Epidemiology and Public Health University of Maryland School of Medicine

2. Domains of Functioning Physical Cognitive Psychological Sensory Social

3. Disability Expression of a physical or mental limitation in a social context The gap between a person’s capabilities and the demands of the environment IOM, 1991

4. Disability Domains Self-care: ADLs Independence living in the community: IADLs Mobility (ambulation) at home and in the community: Mobility disability

5. Activities of Daily Living: ADLs Basic Self-Care Tasks Eating Dressing Bathing Transferring from bed to chair Using the toilet

6. Instrumental Activities of Daily Living: IADLS Preparing meals Shopping Housekeeping Managing money Taking medications Using the telephone

7. Prevalence of Difficulty Walking ¼ Mile, NHIS, 1998 Percent Men Women 29.4 37.5 45.0 57.0 70.2 80.1 0 20 40 60 80 65-7475-8485+65-7475-8485+ Ability to move through one’s environment without assistance Efficient and reliable locomotion is a fundamental feature of human functioning, and indeed functioning across virtually all animal species Mobility

11. Proportion of Persons with Catastrophic and Progressive Disability Among Those Who Developed Severe Disability Catastrophic disability Progressive disability Proportion of the severely disabled 100 80 60 40 20 0 Source: Ferrucci et al. J Gerontol Med Sci 1996;51A:M123-M130. Age (years) 69-74 75-7980-8485+ M M M M W W W W

12. Disability Demographics Behavioral risk factors Disease

13. Disability Functional Limitations Restrictions in basic physical and mental actions (ambulate, reach, grasp, climb stairs, speak, see standard print) Impairments Dysfunction and structural abnormalities in specific body systems (musculoskeletal, cardiovascular, etc.) Demographics Behavioral risk factors Disease Theoretical Model of the Pathway from Disease to Disability: Nagi

14. Mean Grip Strength in Nonsurvivors and Survivors at Baseline and Survivors at Follow-up 27 Years Later Honolulu Heart Program and Honolulu Asia Aging Study Source: Rantanen et al. J Appl Physiol 1998;85:2047

15. Mortality Rates in Groups Based on BMI and Hand Grip Strength Honolulu-Asia Aging Study Source: Rantanen et al. J Gerontol Med Sci 2000;55:M168-73.

16. Proportion of Subjects with Functional Limitations in 1991-93 According to Grip Strength Tertiles 25 Years Earlier Highest Middle Lowest Grip Strength Tertiles Percent Unable to Rise from a Chair Walking Speed  0.4 m/s Functional Limitations (3,218 Initially Healthy 45- to 68-year-old Men, HAAS) Source: Rantanen et al. JAMA 1999;281:558-560. 051015202530

17. Proportion of Subjects with Disability in 1991-93 According to Grip Strength Tertiles 25 Years Earlier Highest Middle Lowest Grip Strength Tertiles Doing Heavy Household Work Self-reported Difficulty Percent (3,218 Initially Healthy 45- to 68-year-old Men, Honolulu) Source: Rantanen et al., JAMA 1999;281:558-560. Toileting Dressing Walking Up 10 Step Walking 1/2 mile 051015202530

18. Sarcopenia The age-related loss in skeletal muscle Sarx = flesh, penia = poverty – IR Rosenberg. Am J Clin Nutr 1989;50(suppl):1231-3 – WJ Evans & WW Campbell. J Nutr 1993;123:465-8

19. The Sarcopenia Hypothesis Muscle mass is lost progressively after mid-adulthood Muscle mass correlates with strength Low strength is a hallmark of disability Many disabling conditions are associated with accelerated loss of lean mass

20. Age-related changes in body composition Age 63 Age 79 John Turner – Weight Lifter

21. Mid-Femur CT Images from the BLSA (all women with BMI 30-32) Age=80 Years Age=55 Years Age=33 Years

22. Dual Energy X-ray Absorptiometry (DEXA)

23. Skeletal muscle mass and distribution in 468 men and women aged 18–88 yr IAN JANSSEN, STEVEN B. HEYMSFIELD, ZIMIAN WANG, and ROBERT ROSS J Appl Physiol 89:81-88, 2000 Men Women

24. The Effect of Bed Rest on Muscle Over 2 pounds of muscle in the legs (6.3% decline) More than 15% of lower extremity strength After 10 days of bed rest, healthy older adults lost… Kortebein et al. JAMA 2007;297:1772-4.

25. Longitudinal Percent Change in Muscle Strength by Decade 25-98 yrs. The Baltimore Longitudinal Study of Aging

26. Annualized declines in leg lean mass (hatched bar) and muscle strength (black bar) in the Health ABC Study. Goodpaster BH et al. The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study. J Gerontol A Biol Sci Med Sci. 2006;61:M1059-M1064.

27. Hazard Ratios for Incident Mobility Limitations by Quartiles of Three Muscle Parameters: Health ABC - WOMEN Adjusted for: age, race, site, height, total fat mass, education, alcohol, smoking status physical activity, prevalent disease, self-rated health, depression, cognition and other parameters. Visser et al, J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):324-33

28. Muscle Mass and Muscle Strength are Not Equivalent Interventions that increase lean mass don’t necessarily increase strength (e.g. GH). Strength increases seen with resistance training precede and are far in excess of measurable changes in muscle mass. Voluntary weight loss leads to losses in skeletal mass but not changes in strength. Therefore, muscle mass alone is not adequate for characterizing or diagnosing sarcopenia.

29. European Working Group on Sarcopenia in Older People 1 Low Muscle Mass and Low Muscle Strength or Low Physical Performance 1.Cruz-Jentoft AJ et al. Age and Ageing 2010;39:412-423 2.Muscaritoli M et al Clinical Nutrition 2010;29:154-159 ESPEN’s Cachexia-Anorexia & Nutrition in Geriatrics SIGs 2 % muscle mass ≥ 2 sd below young adults matched on sex and ethnicity, and Low gait speed (e.g. < 0.8 m/s over 4 meters) New Composite Definitions

30. “See, the problem with doing things to prolong your life is that all the extra years come at the end, when you’re old.”