A vs. B s i l e d e s i l

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1 BODY COMPOSITION OVER THE LIFE CYCLE SARCOPENIA: NORMAL vs. PATHOLOGIC Steven B. Heymsfield Pennington Biomedical Research Center Baton Rouge, LA 1 / GE Healthcare Christel Verboven April 2007

2 N umber of US People > age 65 years 2

3 Aging and Skeletal Muscle 1 yr 12 yrs 35 yrs 71 yrs

4 Age-Related Skeletal Muscle Loss Sarcopenia Type Primary II fibers are selectively lost Motor units are reorganized P -Sarcopenia Sarcopenia Severe Sarcopenia Secondary Inactivity Cachexia 4

5 Adipose Tissue Mass Function Height Skeletal Muscle Mass Age Race Outcome 5 / GE Healthcare Christel Verboven April 2007

6 Weight (kg) Mass y = x R 2 = Height (cm) 1.94 BW eight h 2 Skeletal Muscle Mass (kg) SM Mass y = x R 2 = Height (cm) 2.16 SM eight h 2 6 / GE Healthcare Christel Verboven April 2007

7 7 / Verboven GE Healthcare Christel 2007 April RACE AGE SM mass (kg) RACE AGE SM mass (kg) Lifespan the Mass Across Muscle Skeletal LV. hompson, T y Therap hysical P ) ( :71 Contraction Maximal of Percent Old Years 30 at Age (years) Muscle strength Women Men

8 Age-Related Hormonal Changes 8

9 Mismatch between muscle mass and muscle The HABC study strength m ass (%/y) s trength (%/y) Men 0.47 > 75 y Women 0.37 > 75 y Muscle Mass Muscle Strength Adapted from Goodpaster et al

10 Aging & Energy Balance Regulation Roberts, S. B. et al. Physiol Rev 2006

11 % of US People Engaged in Regular Time Physical Activity Leisure RLTPA: engaging in light- m oderate activity > 30 min > 5 days/wk 11

12 2- week Immobilization immobilization single leg soft cast followed by 4- week retraining (strength training) Incomplete recovery neural deficit + Suetta C. et al. JAP

13 The Pathophysiology of Sarcopenia Triggering Event Inflammation ( eg, TNF -α, I L - 6 ) Hormonal changes (eg, decrease in GH, DHEA, e strogen, testosterone, IGF - I ) Metabolic disorders/oxidative stress Decreased physical activity Nutritional deficit (Reduced intake/uptake) Increased protein catabolism Decreased protein synthesis Loss of motor neurons Shift in muscle fiber population Mitochondrial damage Loss of muscle mass s Loss of muscle strength Loss of muscle function n Loss of mobility Aggravating Conditions Respiratory Disease COPD, asthma, lung disease limits physical activit y Metabolic Disorders Reduced glucose sensitivity in sarcopenic skeletal muscle exacerbates glucose intolerance Reduced muscle mass reduces ability for metabolic adaptation Cachexia Sarcopenia is one component of cachexia, a condition of severe muscle and fat loss associated with COPD, cancer, diabetes, cardiovascular disease, and renal disease Osteoporosis Fractures in osteoporotic women can result in forced immobilization and a resulting sarcopenic state. Furthermore, the gait and balance impairment seen in sarcopenia can increase the risk of fractures in osteoporosis Neuropsychiatric Disorders Untreated depression and dementia lead to reduced physical activity, increased resting metabolic rate Involuntary Immobilization Postsurgical immobilization reduces physical activity and results in acute loss of muscle RA/OA Loss of mobility can exacerbate sarcopeni a Underlying inflammatory process in RA may also contribute to the pathophysiology of sarcopenia LOSS OF INDEPENDENCE E 13 Protocol: [Compound]

14 Sarcopenia and Frailty Fried et al., 2001, 2005

15 Adipose Tissue-Skeletal Muscle Relations Women Men 2 SM/Ht SM/Ht AT/Ht 2 AT/Ht 1 kg AT 0.10 kg (W) & 0.24 kg (M) SM 15

16 Adipose Tissue Volume Across the Lifespan Visceral Subcutaneous Weight FFM Skeletal Muscle Total Leg Arm Bone Fat Gallagher AJP / GE Healthcare Christel Verboven April 2007

17 M orbidity Sarcopenia Obesity Body Mass Index 17

18 Other hormonal disturbances Zamboni et al., Nutr Metab CVD 2008;18:388 18

19 Survival Curve for Time to Drop in IADL Non Sarcopenic-Non Obese Non Sarcopenic-Obese Sarcopenic Non-Obese Sarcopenic-Obese Baumgartner et al., Obesity Research 2004;12:

20 Conclusions Growing aging population accompanied by increasing presentation of sarcopenia syndromes and related frailty. Combined sarcopenia and obesity is a silent- disease characterized by increased fat mass that masks reduced SM mass and function; associated with poor outcomes. Mechanism(s) uncertain but likely multifactorial including dysregulation of energy balance, hormonal, inflammatory mediators, neurotrophic effects, reduced activity, and underlying disease; these factors may act synergistically. Important future research opportunity. 20