Weight stability masks sarcopenia in elderly men and women

Dympna Gallagher, Else Ruts, Marjolein Visser, Stanley Heshka, Richard N. Baumgartner, Jack Wang, Richard N. Pierson, F. Xavier Pi-Sunyer and Steven B. Heymsfield
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American Journal of Physiology - Endocrinology and Metabolism publishes results of original studies about endocrine and metabolic systems on any level of organization. It is published 12 times a year (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright 2000 the American Physiological Society. ISSN: 0193-1849, ESSN: 1522-1555. Visit our website at http://www.the-aps.org/.

Am J Physiol Endocrinol Metab 279: E366E375, 2000.

Weight stability masks sarcopenia in elderly men and women

DYMPNA GALLAGHER,1 ELSE RUTS,1 MARJOLEIN VISSER,2 STANLEY HESHKA,1 RICHARD N. BAUMGARTNER,3 JACK WANG,1 RICHARD N. PIERSON,1 F. XAVIER PI-SUNYER,1 AND STEVEN B. HEYMSFIELD1 1 Department of Medicine, Obesity Research Center, St. Lukes-Roosevelt Hospital, Columbia University, New York, New York 10025; 2Faculty of Medicine, Institute for Research in Extramural Medicine, 1081 BT Amsterdam, The Netherlands; and 3Clinical Nutrition Program, Center for Population Health, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131
Received 7 September 1999; accepted in nal form 8 March 2000

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Gallagher, Dympna, Else Ruts, Marjolein Visser, Stanley Heshka, Richard N. Baumgartner, Jack Wang, Richard N. Pierson, F. Xavier Pi-Sunyer, and Steven B. Heymseld. Weight stability masks sarcopenia in elderly men and women. Am J Physiol Endocrinol Metab 279: E366E375, 2000.Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional studies but has not been shown in elderly subjects using appropriate measurement techniques combined with a longitudinal study design. Longitudinal skeletal muscle mass changes after age 60 yr were investigated in independently living, healthy men (n 24) and women (n 54; mean age 73 yr) with a mean SD follow-up time of 4.7 2.3 yr. Measurements included regional skeletal muscle mass, four additional lean components (fat-free body mass, body cell mass, total body water, and bone mineral), and total body fat. Total appendicular skeletal muscle (TSM) mass decreased in men ( 0.8 1.2 kg, P 0.002), consisting of leg skeletal muscle (LSM) loss ( 0.7 0.8 kg, P 0.001) and a trend toward loss of arm skeletal muscle (ASM; 0.2 0.4 kg, P 0.06). In women, TSM mass decreased ( 0.4 1.2 kg, P 0.006) and consisted of LSM loss ( 0.3 0.8 kg, P 0.005) and a tendency for a loss of ASM ( 0.1 0.6 kg, P 0.20). Multiple regression modeling indicates greater rates of LSM loss in men. Body weight in men at follow-up did not change significantly ( 0.5 3.0 kg, P 0.44) and fat mass increased ( 1.2 2.4 kg, P 0.03). Body weight and fat mass in women were nonsignicantly reduced ( 0.8 3.9 kg, P 0.15 and 0.8 3.5 kg, P 0.12). These observations suggest that sarcopenia is a progressive process, particularly in elderly men, and occurs even in healthy independently living older adults who may not manifest weight loss. aging; body composition; skeletal muscle mass; longitudinal study

and humans is associated with body composition changes and related functional decline (9). Cross-sectional population studies in humans suggest that body weight (1, 21, 22) and fatness increase (4) up to the sixth decade with a gradual decline thereafter in body weight (35), skeletal muscle
SENESCENCE IN BOTH ANIMALS

mass (10, 35, 36), and bone mineral (29, 30). Frailty and sarcopenia may represent the advanced stages of progressive age-related body composition changes (6, 32). Weakness, falls, functional limitations, immobility, and osteoporotic fractures may be linked to declines in musculoskeletal mass (6, 32). Although substantial information exists on the nature of skeletal muscle mass and related skeletal changes in old age, available information represents analyses based largely on cross-sectional studies (2, 12) that often relied on measurement methods of questionable validity and accuracy (e.g., urinary creatinine and anthropometry) or with small sample sizes (3). These reports frequently failed to exclude elderly subjects with chronic wasting diseases (37) and those who had recently dieted for weight loss. A fundamental and as yet unanswered question concerns the magnitude of longitudinal age-related skeletal muscle mass loss in the absence of clinically evident disease in weightstable elderly subjects. A recent cross-sectional study of healthy adults examined the interrelationships among appendicular skeletal muscle mass, age, and gender (12). Although both older women and men had less absolute amounts of skeletal muscle compared with their younger counterparts, after adjustment for height and weight, relative reductions were larger in men. A compilation by Forbes (9) of cross-sectional body composition studies from infancy to old age arrived at a similar conclusion. These observations imply that, in men, the absolute rate of decline in skeletal muscle mass with senescence exceeds that in women, but whether or not these ndings apply to a longitudinally evaluated healthy and mobile elderly population remains uncertain. The present study was designed to evaluate skeletal muscle mass loss over time in healthy communitydwelling and independently living elderly adults. Specically, the hypothesis was that, after excluding per-

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sons with underlying disease and voluntary weight loss, there is an ongoing reduction of skeletal muscle mass. A secondary aim of the study was to explore previously reported (9, 12) gender differences in the rate of age-related skeletal muscle decline.
METHODS

Subject Recruitment Clinical status and body composition were longitudinally monitored in a cohort of healthy men and women. The primary subject recruitment pool consisted of 1,449 healthy adults who were tested between 1986 and 1994 (Fig. 1) as part of an ongoing study at the Body Composition Unit of the New York Obesity Research Center (12, 13, 38). Changes in body composition instrumentation with the replacement of dual photon absorptiometry by dual-energy X-ray absorptiometry (DEXA) occurred in May 1989. Between May 1989 and December 1994, 261 subjects over the age of 60 yr at the time of initial study had been evaluated. This group was targeted to participate in the follow-up study. The study cohort was developed by attempting to contact these 261 subjects. Contact was made with 170 (65%) of the 261 elderly subjects. Of the 170 subjects contacted, 100 (59%) agreed to return for evaluation during the years 1995 to 1997, a follow-up time ranging from 1 to 9 yr in men and 1 to 10 yr in women. The remaining 70 subjects (41%) were not willing to participate or were excluded due to health reasons (e.g., self-reported cancer, cerebrovascular disease, nonambulatory physical disability, or serious chronic illness). Subjects with high blood pressure adequately controlled with medications and with nonclinically signicant conditions such as mild osteoarthritis were not excluded. During follow-up, each subject completed a medical examination that included screening blood tests after an overnight fast. Blood samples were sent to a commercial laboratory (Corning Clinical Laboratories and Quest Diagnostics, Teterboro, NJ) for analysis. Of the 100 medically evaluated subjects, of whom 71 were women and 29 were men, 22 were excluded for the following reasons: one male was an outlier with regard to age (baseline age of 107 yr, far beyond the age range of remaining subjects); intentional diet-related weight loss ( 10 kg; n 6); relapse from previous diet with weight gain between baseline and follow-up evaluations ( 5 kg; n 5); diabetes mellitus based on self report of physician-diagnosed disease (n 5); double hip replacement (n 1); endurance exerciser (bicycler, runner, mountain climber 10 yr; n 1); or cancer (n 3). A total of 78 healthy, weight stable subjects, 54 women and 24 men, were included in the statistical analyses. The study was approved by the Institutional Review Board of St. Lukes-Roosevelt Hospital, and subjects gave written consent before participation. Body Composition Subjects reported in a fasted state to the Body Composition Core Laboratory in the morning. They then donned hospital gowns and foam slippers. Body weight and height were measured to the nearest 0.1 kg (Weight Tronix, New York, NY) and 0.5 cm (Holtain Stadiometer, Crosswell, Wales), respectively. Skeletal muscle and four related lean components (i.e., fat-free body mass, body cell mass, total body water, and bone mineral mass) along with total body fat were monitored over

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Fig. 1. Flow chart of enrollment in the study. IWL, intentional weight loss; WR, weight regain; DHR, double hip replacement; EE, endurance exerciser.

time. Skeletal muscle compartments of the arms and legs were quantied using regional DEXA-measured lean soft tissue. Total appendicular skeletal muscle was calculated as the sum of arm and leg lean soft tissue (14). Fat was measured by DEXA, and fat-free body mass was then calculated as the difference between body weight and total body fat. Total body bone mineral mass was also evaluated using DEXA. Total body water, which usually represents 7075% of fat-free body mass (39), was measured using tritiated water (3H2O). Body cell mass was derived from total body potassium as measured with a 4-pi 40K whole body counter (23). DEXA Body composition was measured with whole body DEXA (Lunar Radiation, Madison, WI) operated in slow scan mode. Software version 3.6 was used to analyze all of the DEXA scans. The system software provided estimates of the following three compartments: fat, lean soft tissue, and bone mineral for the whole body and specic regions. Fat-free body mass was calculated as the sum of lean soft tissue and bone mineral. Regional measurements were made separately for the legs and arms (14). With the use of anatomic landmarks, the legs (i.e., soft tissue extending from a computer-generated line drawn through and perpendicular to the axis of the femoral neck and angled with the pelvic brim to the phalange tips) and arms (i.e., soft tissue extending from the center of the arm socket to phalange tips) were rst isolated on the skeletal DEXA anterior view planogram. System software then provided estimates of leg and arm fat, lean soft tissue, and bone mineral mass. The fat and bone mineral-free portion of the arms and legs was assumed to represent leg and arm appendicular skeletal muscle mass along with a small and relatively constant amount of skin and underlying connective

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tissue (14). Repeated daily measurements over 5 days in four subjects showed a coefcient of variation (CV) of 1.7% for leg, 2.0% for arm, and 2.6% for total appendicular skeletal muscle. Body composition estimates were all acquired on the same DEXA system, and software version 3.6 was used for data analysis at baseline and follow-up. An anthropomorphic spine phantom made up of calcium hydroxyapatite embedded in a 17.5 15 17.5-cm block was scanned for quality control each morning before subject evaluation. The phantom was also scanned immediately before and after all DEXA system manufacturer maintenance visits. The measured phantom bone mineral density was stable throughout the study period at 1.1661.196 g/cm2. Ethanol and water bottles (8-liter volume), simulating fat and fat-free soft tissues, respectively, were scanned as soft tissue quality control markers monthly. The range in measured R values over the study period was 1.2551.258 (CV 0.127%) and 1.3671.371 (CV 0.103%) for ethanol and water, respectively. Whole Body Counting The St. Lukes 4-pi whole body counter was used to measure 40K (23). The 40K raw counts accumulated over 9 min were adjusted for self-absorption of the 1.46 meV -ray emission by a 42K calibration equation based on body size (26). The within-subject CV in our laboratory for 40K counting is 4% (25). Total body potassium, in millimoles, was calculated as 40K/0.0118. Body cell mass was calculated from total body potassium as body cell mass (kg) 0.00833 TBK (mmol). This equation is based on two assumptions, that the average intracellular potassium content is 3 mmol/g of nitrogen and that the nitrogen content is 0.04 g/g wet tissue (19). There is good support for these assumptions in weight-stable healthy women and men across a wide age spectrum (5, 18). Counting efciency was measured continuously throughout the study by evaluating calibration standards in the form of 10-lb ( 4 kg) plastic bottles containing potassium chloride (5,000 dpm of 40K) in distilled water. At the beginning of each study day, bottles approximating the body size and weight of each subject were counted. The between-day CV for 40K counting of calibration standards over the study period was 2.4%. Radiolabeled Water Dilution A blood sample was taken before and 3 h after subjects received 200 Ci (7.4 mBq) of 3H2O (24). Total body water volume was estimated as the 3H2O dilution space multiplied by 0.96, to correct for nonaqueous hydrogen exchange (28). Total body water in kilograms was calculated as the product of total body water volume and density at 37C (i.e., 0.994 g/cm3). The within-subject CV for repeated 3H2O dilution volume estimates is 1.5% (28). An 8-liter plastic bottle containing an accurately measured 6-liter quantity of tap water was used as a daily quality control phantom, with tracer dosage proportional to individual study subject body weight. The CV for repeated phantom measurements was 1.3% over the study interval. Statistical Methods Power calculation. The power to test the main hypothesis was based on the change in total appendicular skeletal muscle of 0.4 kg/decade and 0.8 kg/decade for women and men respectively, in the cross-sectional cohort reported by Gallagher et al. (12), using the same methodology. Repeated

DEXA measures scanned over 5 days on four subjects indicated a between-day SD for total appendicular skeletal muscle of 0.53 kg. With the use of these estimates of change and variability, the power to detect a change from baseline of 0.2 kg in women was 0.83, with a sample size of 50. The power to detect a change from baseline of 0.4 kg in men was 0.97, with a sample size of 25. Data analysis. The hypothesis was tested that, after excluding persons with underlying disease and voluntary weight loss, there is an ongoing erosion of appendicular skeletal muscle mass in aging men and women. The statistical signicance of longitudinal changes in total appendicular skeletal muscle mass was tested within each gender using paired t-tests. Pearson correlation coefcients were used to quantify bivariate relationships between change in appendicular skeletal muscle and corresponding changes in other lean components, fat-free body mass, total body water, body cell mass, and bone mineral. The relationships between changes over time in appendicular skeletal muscle and baseline appendicular skeletal muscle, age, gender, and follow-up interval were investigated using multiple regression analysis. The observed change in appendicular skeletal muscle was set as the dependent variable, and baseline appendicular skeletal muscle, age, gender, and follow-up interval were added to the regression model as independent variables. In the analyses, two -tailed levels of 0.05 were considered statistically signicant. Longitudinal changes in other measured body compartments and baseline gender, demographic, and body composition differences were tested for statistical signicance using paired and unpaired t-tests. These descriptive analyses were considered borderline or statistically signicant with P 0.10 and P 0.05, respectively. Several subjects were, on occasion, unable to complete all of the evaluations due to technical and personal reasons, and the reduction in sample size is identied in RESULTS. Three of the 54 women were currently receiving estrogen replacement therapy. Analysis of the data with and without the subjects on estrogen replacement gave similar results, and these subjects have therefore been retained in the analyses. Data were analyzed using SAS statistical software version 6.12 (SAS Institute, Cary, NC), and group results are presented as means SD in text and as means SE in Figs. 14.
RESULTS

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Subject Characteristics The baseline and follow-up subject descriptive characteristics are summarized in Table 1. Men and women were similar in age at baseline (72.9 5.5 and 70.2 7.8 yr, range 6090 yr) and follow-up (77.8 6.5 and 74.8 7.8 yr, range 6296 yr). Men were heavier (P 0.001) and taller (P 0.001) than women, and there were no signicant gender differences in body mass index or in the percentage of subjects who were currently smoking. The mean follow-up interval for the study population was 4.7 2.3 yr and was similar (P 0.64) for men (4.9 2.4 yr) and women (4.6 2.3 yr). Longitudinal Body Composition Changes The changes observed in body composition compartments from baseline to follow-up evaluation, expressed as absolute values and as annualized rates, are reported in Table 2 for men and in Table 3 for women.

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Table 1. Subject characteristics at time of baseline and follow-up evaluations

Men (n Baseline 24) Follow-up Baseline Women (n 54) Follow-up

Age, yr Body weight, kg Height, m Body mass index, kg/m2 Values are means

72.9 5.8 (6690) 71.9 12.6 (55.8103.4) 1.71 0.07 (153.5185.5) 24.6 3.5 (19.936.0)

77.8 6.5 (6996) 71.5 12.7 (54.0105.1) 1.70 0.07 (153.3183.3) 24.7 3.7 (20.136.9)

70.2 7.8 (6087) 61.8 11.5* (36.8885.1) 1.57 0.07* (1.441.70) 24.9 4.3 (16.934.0)

74.8 7.8 (6290) 61.0 12.0 (36.886.8) 1.57 0.07 (1.431.69) 24.8 4.5 (16.135.2)

SE with ranges in parentheses; n, no. of subjects. * P

0.05 for between-gender comparisons at baseline.

Men. Total appendicular skeletal muscle mass decreased signicantly in the men both as an absolute change ( 0.8 1.2 kg, P 0.002) and as a percentage of baseline skeletal muscle mass ( 3.3 4.5%, P 0.001). The reduction in men of total appendicular skeletal muscle mass consisted of a signicant lowering of leg ( 0.7 0.8 kg, P 0.001) and a borderline signicant lowering of arm ( 0.2 0.4 kg, P 0.06) skeletal muscle mass. The annual rate of total appendicular skeletal muscle mass change in the men was 0.2 0.5 kg/yr. The absolute change in leg skeletal muscle mass as a function of age is presented in Fig. 2 for each male subject. From the total sample of 24 men, 21 (87.5%) showed a decrease or no change ( 0. 5 kg) in leg appendicular skeletal muscle from baseline to followup. The remaining 3 men (15%) showed an increase ( 0. 5 kg) in leg appendicular skeletal muscle. There was also a signicant reduction in men of fat-free body mass ( 1.4 1.9 kg, P 0.002) and one of its main components, total body water ( 1.4 2.9 kg, P 0.04). Other fat-free body mass components such as body cell mass and bone mineral mass also decreased over time in men, although the changes were

either borderline or not statistically signicant ( 0.8 2.0 kg, P 0.08 and 0.023 0.122 kg, P 0.38). The relative loss of bone mineral in men, 0.7 4.2%, was substantially less than that observed for skeletal muscle ( 3.3%). Accordingly, there was a signicant decrease from baseline in the ratio of appendicular skeletal muscle mass to bone mineral (16.1 3.2 to 15.6 4.1 kg/kg, P 0.011). In contrast to signicant lean losses, there was no signicant change in body weight ( 0.5 3.0 kg, P 0.44), and fat mass increased signicantly ( 1.2 2.4 kg, P 0.03). The changes in body weight and body composition components in men are summarized in Fig. 3. The observed 0.5-kg decrease in body weight was mainly reective of a combined decrease in fat-free body mass ( 1.4 kg) and an increase in fat mass ( 1.2 kg). Of the observed decrease in fat-free body mass, 15% was arm ( 0.2 kg) and 54% was leg ( 0.7 kg) skeletal muscle. Therefore, arm and leg skeletal muscle combined accounted for 69% of fat-free mass loss. The observed change in bone mineral mass accounted for 1% ( 0.023 kg) of fat-free mass loss.

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Table 2. Results of longitudinal body composition studies in men

Baseline, kg Follow-up, kg Change, kg Change, kg/yr P* Change P Gender

Body weight Fat Fat-free body mass Arm muscle Leg muscle Total appendicular muscle Body cell mass Total body water Bone mineral

71.9 12.6 (55.8103.4) 15.4 6.7 (6.637.2) 56.2 8.0 (44.973.0) 6.1 1.3 (4.48.8) 18.8 3.1 (15.025.1) 24.9 4.3 (19.633.9) 25.4 3.5 (17.931.0) 39.5 7.0 (25.054.0) 2.896 0.566 (2.0844.50)

71.5 12.7 (54.0105.1) 16.6 7.5 (7.641.9) 54.9 7.5 (42.768.5) 5.9 1.2 (4.18.3) 18.1 3.0 (13.923.2) 24.1 4.1 (18.731.1) 24.6 3.8 (19.534.6) 37.7 6.2 (29.050.0) 2.874 0.563 (2.0224.50)

0.5 3.0 ( 5.56.6) 1.2 2.4 ( 4.56.3) 1.4 1.9 ( 4.62.7) 0.2 0.4 ( 1.00.6) 0.7 0.8 ( 2.01.3) 0.8 1.2 ( 2.91.5) 0.8 2.0 ( 4.93.7) 1.4 2.9 ( 8.06.0) 0.023 0.122 ( 0.3780.179)

0.1 0.3 0.3 0.1 0.2 0.2 0.2 0.4 0.002

0.9 0.5 0.8 0.1 0.3 0.5 0.5 0.9 0.03

0.44 0.03 0.002 0.06 0.001 0.002 0.08 0.04 0.38

0.76 0.003 0.002 0.27 0.05 0.08 0.16 0.42 0.61

Values are means SD with ranges in parentheses; n 24 subjects except for body cell mass, where n water, where n 21. * For baseline vs. follow-up comparison. For absolute change in men vs. women.

22 subjects, and total body

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Table 3. Results of longitudinal body composition studies in women

Baseline, kg Follow-up, kg Change, kg Change, kg/yr P* Change

Body weight Fat Fat-free body mass Arm muscle Leg muscle Total appendicular muscle Body cell mass Total body water Bone mineral

61.8 11.5 (36.885.1) 21.9 8.6 (6.939.0) 39.3 4.5 (28.747.1) 3.8 0.7 (2.15.6) 12.6 1.7 (8.016.0) 16.4 2.8 (10.321.5) 17.1 1.8 (12.420.8) 29.7 4.0 (22.039.0) 1.984 0.391 (1.3073.052)

61.0 12.0 (36.886.8) 21.1 9.2 (4.637.8) 39.3 4.3 (28.847.0) 3.7 0.8 (2.45.1) 12.3 1.6 (8.516.0) 15.9 2.2 (10.821.1) 16.8 2.0 (12.021.5) 28.8 4.3 (20.036.0) 1.948 0.372 (1.3412.962)

0.8 3.9 ( 8.19.9) 0.8 3.5 ( 9.77.5) 0.02 1.4 ( 3.32.3) 0.1 0.6 ( 0.010.6) 0.3 0.8 ( 0.021.9) 0.4 1.2 ( 2.92.4) 0.3 1.3 ( 3.72.8) 0.9 2.1 ( 8.03.6) 0.036 0.106 (0.30.208)

0.2 1.1 0.2 1.3 0.0 0.5 0.03 0.3 0.1 0.3 0.1 0.4 0.04 0.3 0.01 2.0 0.008 0.04

0.15 0.12 0.93 0.20 0.005 0.006 0.11 0.005 0.02

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Values are means SE with ranges in parentheses; n 54 subjects except for body cell mass, where n 50 subjects. * For baseline vs. follow-up comparison.

47, and total body water, where

Women. The absolute and relative changes in total appendicular skeletal muscle mass in women were 0.4 1.2 kg (P 0.006) and 2.2 7.1% (P 0.001), respectively. The reduction in women of total appendicular skeletal muscle mass consisted of a signicant lowering of leg skeletal muscle mass ( 0.3 0.8 kg, P 0.005) and a nonsignicant reduction in arm skeletal muscle mass ( 0.1 0.6 kg, P 0.20). The annual rate of total appendicular skeletal muscle mass change in women was 0.1 0.4 kg/yr. From the total sample of 54 women, 46 (85%) showed a decrease ( 0.5 kg) or no change in leg appendicular skeletal muscle from baseline to follow-up. The remaining 8 women (17%) showed an increase ( 0. 5 kg) in leg appendicular skeletal muscle. There was a negligible change in fat-free body mass ( 0.02 1.4 kg, P 0.93) and a signicant reduction

in total body water ( 0.9 2.1 kg, P 0.005). Body cell mass and bone mineral mass also decreased ( 0.30 1.3 kg, P 0.11; and 0.036 0.106 kg, P 0.02) over the study period in the women. The loss of bone mineral in women, 1.6 5.1%, was similar to that observed for skeletal muscle ( 2.2 7.1%). There was no signicant change from baseline in the ratio of appendicular skeletal muscle to bone mineral (16.9 4.9 to 16.8 5.3 kg/kg, P 0.61). Body weight and fat mass in women also decreased over the study interval, although nonsignicantly by 0.8 3.9 kg (P 0.15) and 0.8 3.5 kg (P 0.12), respectively. Figure 4 shows the observed longitudinal changes in body weight and body composition components in women. The observed 0.8-kg decrease in body weight was reective of a loss in fat mass ( 0.8 kg) with no

Fig. 2. Leg skeletal muscle (kg) at baseline and follow-up in individual male subjects vs. age.

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Fig. 3. Changes ( SE) over study period in body weight and body composition components in men. FFM, fat-free mass; TSM, total skeletal muscle; LSM, leg skeletal muscle; ASM, arm skeletal muscle; BM, bone mineral.

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change in measured fat-free mass ( 0.02 kg). However, within the fat-free mass compartment, there was a 0.1-kg loss of arm and a 0.3-kg loss of leg skeletal muscle, and a small increase in lean soft tissue of the trunk accounted for the difference between unchanged fat-free mass and appendicular skeletal muscle loss. The observed change in bone mineral was 0.036 kg. Bivariate correlations. The bivariate correlations between changes in total and leg appendicular skeletal muscle mass and changes in other lean components are summarized in Table 4. The pattern for both total and leg skeletal muscle was similar, with signicant or borderline signicant associations observed with parallel changes in all other lean compartments, including fat-free body mass, total body water, and body cell mass.

Gender Differences Neither women nor men had statistically signicant reductions in body weight. However, fat mass increased signicantly in men (P 0.03) and decreased nonsignicantly (P 0.12) in women. The gender difference in longitudinal changes in fat mass was statistically signicant (P 0.003). The absolute change in total appendicular skeletal muscle was larger in men than in women (P 0.08) and consisted of a nonsignicant difference in arm (P 0.27) and a signicant difference in leg skeletal muscle change (P 0.05; Tables 2 and 3). A similar gender difference was observed in absolute fat-free mass change (P 0.002). Multiple regression analysis of the pooled data with change in leg skeletal muscle as the

Fig. 4. Changes ( SE) over study period in body weight and body composition components in women.

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dependent variable indicated two signicant independent variables, baseline leg skeletal muscle mass (P 0.002) and follow-up interval (P 0.01). Gender entered the regression model as borderline signicant (P 0.09), and baseline age did not enter as a significant independent variable in the regression model (Table 5). Of the 78 evaluated subjects, there were 31 (11 men and 20 women) whose follow-up interval was 6 yr. The mean follow-up time for both men and women in this cohort was identical at 7.1 1.2 yr. The absolute changes in total appendicular skeletal muscle were 1.1 1.1 kg in the men (P 0.005) and 0.6 1.0 kg in the women (P 0.012). Multiple regression analysis of the pooled data for this sample with change in leg skeletal muscle as the dependent variable indicated two signicant independent variables, baseline leg skeletal muscle mass (P 0.02) and gender (P 0.005; total model R2 0.27, SE of the estimate 0.6 kg). Gender, follow-up interval, and baseline age were not statistically signicant independent variables when multiple regression models were developed with changes in body weight, fat mass, fat-free mass, and bone mineral as the dependent variables. Baseline fat-free mass entered the fat-free mass change model as a signicant covariate; thus larger baseline values were associated with greater loss over time.
DISCUSSION

Table 5. Multiple-regression analysis for leg skeletal muscle

Leg Skeletal Muscle, kg Mean SE P

Gender (0 women, 1 man) Follow-up interval, yr Age at baseline, yr Baseline leg skeletal muscle, kg Intercept R2 SEE

0.55 0.32 0.10 0.04 0.02 0.01 0.13 0.04 3.17 1.11 0.22 0.77

0.09 0.01 0.13 0.002 0.006

R2, explained variance of total model; SEE, standard error of estimate.

This study supports the hypothesis that loss of skeletal muscle mass occurs with advancing age in elderly men and women, even in independently living healthy subjects. An additional observation, in support of earlier cross-sectional studies, is that men lost signicantly more leg skeletal muscle mass than did women over the study interval. Skeletal muscle mass loss in men was masked by weight stability resulting from a corresponding increase in total body fat mass. Progression of sarcopenia, particularly in men, may therefore be clinically silent and comparable to loss of bone mineral in osteoporosis. Aging and Skeletal Muscle Loss Evidence ranging from tissue biochemical (27, 31) to gross anatomic (17) changes in cross-sectional samples provides strong but indirect evidence of age-related Table 4. Bivariate correlations between changes in appendicular skeletal muscle mass and changes in other body compartments
All Subjects

Total skeletal muscle Fat-free body mass Body cell mass Total body water Leg skeletal muscle Fat-free body mass Body cell mass Total body water , Change. * P 0.05 and P 0.1.

0.74* 0.28* 0.22 0.68* 0.29* 0.22

skeletal muscle loss or sarcopenia. Interpretation of skeletal muscle changes in cross-sectional samples is, however, limited due to potential cohort effects and secular trends. Additionally, the body composition changes observed in most of the earlier studies lacked adequate adjustment for confounding factors such as subject weight, stature, and health status. Moreover, the applied body composition methods, such as urinary creatinine and anthropometry (22), were often limited in accuracy and had inadequate power to measure small changes in the skeletal muscle compartment. The present investigation was designed to overcome the limitations of these earlier studies by specically evaluating appendicular skeletal muscle and four closely related whole body components (fat-free body mass, body cell mass, total body water, and total body bone mineral mass). Our ndings show, unequivocally, that independently living healthy elderly adults experience an ongoing decline in skeletal muscle mass and related lean components. A large proportion ( 7580%) of skeletal muscle is water (33), and over one-half of the total body potassium pool is within the cellular matrix of skeletal muscle bers. Moreover, skeletal muscle accounts for more than one-half ( 55%) of total fat-free body mass (33). The observation of concurrent signicant or borderline signicant reductions in fat-free body mass, appendicular skeletal muscle, body cell mass, and total body water strengthens our study results and conrms earlier longitudinal observations. Steen et al. (35) observed a signicant loss of total body water after a 5-yr follow-up of 28 Swedish 70-yr-old men ( 3.0 kg or 2%; P 0.05) and 37 women ( 2.0 kg or 2%; P 0.05). Body weight and body cell mass in the Swedish subjects also decreased signicantly in both sexes from ages 70 to 75 yr (men, body weight and cell mass, 2.9 and 1.0 kg; women, body weight and cell mass, 1.7 and 0.6 kg; all P 0.05), whereas body fat increased signicantly in men only ( 0.8 kg, P 0.05; women, 0.6 kg, P not signicant). Flynn et al. (8) observed an age-related signicant decline in total body potassium (i.e., body cell mass) in 564 longitudinally monitored men (14%) and 61 women (13%) who were followed over an 18-yr study interval. Signicant declines in body mass index ( 0.7%, P 0.05) and the creatinine-to-height ratio (i.e., an index of skeletal muscle

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mass; 4.6%, P 0.05) were observed in 445 men ( 60 yr) who were monitored in the Baltimore Longitudinal Study of Aging (20) over a 2.6-yr mean follow-up interval. Our observations, combined with these earlier reports, indicate a dynamic remodeling of body composition as independently living healthy older adults advance in age. Fat mass remains unchanged or may even increase, whereas there are consistent losses of lean tissues, including the large fat-free body mass component and its constituent skeletal muscle mass, body cell mass, total body water, and bone mineral mass. As suggested by results from earlier cross-sectional studies (12), men and women between the ages of 20 and 60 yr have reductions in total appendicular skeletal muscle mass of 3.2 kg (11%) and 1.6 kg (8%), respectively. From these studies, estimates of skeletal muscle loss, expressed per decade, are 0.8 kg for men and 0.4 kg for women. A recent cross-sectional study of older men (ages 4985 yr) suggested a 1.2 kg/decade loss of appendicular skeletal muscle (34). The longitudinal observations in our elderly cohort with a mean age 70 yr indicate per decade rates of appendicular skeletal muscle loss of 1.6 kg and 0.6 kg in men and women, respectively. The possibility exists that crosssectional studies have underestimated actual rates of skeletal muscle loss and that losses of skeletal muscle with aging are nonlinear and may accelerate in older age groups. An important question is what mechanisms were responsible for skeletal muscle mass loss in our subjects. Disuse is a well-recognized cause of skeletal muscle atrophy, although none of our subjects reported physical disabilities. Catabolic conditions, such as rheumatoid arthritis and certain malignancies, are associated with negative protein balance and skeletal muscle atrophy. Weight loss when voluntarily carried out by subjects controlling their body weight also produces loss of lean tissue, including skeletal muscle. We excluded subjects in the present study who were nonambulatory, had physical disabilities, serious chronic illnesses, or who had experienced recent voluntary weight loss. Hence, such mediating factors are likely not the basis for the skeletal muscle atrophy observed in the present study. Our ndings do suggest that future mechanistic studies need not exclude from analysis healthy, ambulatory, and weight-stable elderly subjects. Gender Differences An important observation in the present study was that the relative rate of skeletal muscle loss in men substantially exceeded the relative rate of bone mineral loss. In women, the relative losses of skeletal muscle and bone proceeded at similar rates. Aging men and women would therefore be anticipated to develop very different musculoskeletal relationships in old age. Falls, weakness, frailty, and ultimately fractures can potentially arise from changes in bone composition and quality, a loss of supporting and protective skeletal

muscle, or a combination of the two. Our observations suggest that in elderly men there is a predominant skeletal muscle loss, whereas in women proportional reductions occur in both skeletal muscle and bone. These ndings point toward a possible gender difference in the pathophysiology of osteoporotic fractures and also suggest potentially different prevention strategies in men and women. The absolute loss of leg skeletal muscle mass was greater in men than in women (P 0.05) over the study period, conrming the earlier cross-sectional ndings of Gallagher et al. (12) that were also based on DEXA measurements. Forbes and Reina (10) reviewed available literature on urinary creatinine excretion, a measure of fat-free and skeletal muscle mass, in subjects ranging in age from 1 to 80 yr. Creatinine excretion was lower in older subjects, particularly men, compared with young adults. This observation was supported by a similar analysis of available literature on total body potassium (9). In the 18-yr longitudinal study by Flynn et al. (8), there was a greater total body potassium loss in men (9%) compared with women (2%) between the ages 41 and 60 yr. After age 60 yr, the investigators observed a similar rate of total body potassium loss in men (7%) and women (9%). Although these observations suggest that the magnitude of skeletal muscle loss over time is greater in men than in women, this difference is partially accounted for by the larger initial muscle mass in men as shown in our regression analysis. The remaining gender effect was only borderline signicant in the whole cohort (follow-up range 110 yr) but became statistically significant in those subjects followed for 6 yr. Implications The current study demonstrates that weight stability in older individuals does not imply body composition stability. The nding of signicant muscle loss in what likely presents as a healthier than normal group of elderly adults, while maintaining weight stability, exposes sarcopenia as a silent, progressive phenomenon, similar perhaps to osteoporosis. Although the current study cannot directly attest to the consequences of observed skeletal muscle changes, the loss of leg skeletal muscle mass and reductions in muscle strength may have implications for overall mobility and physical function. Hip fracture risk in older subjects (15, 16) is higher for persons who lose more weight starting at age 50 in men and 65 in women. Conversely, a weight increase of 10% or more reduces the risk (15). An argument could therefore be made that, even in older weight-stable men and women where known leg muscle atrophy is occurring, the risk of hip fracture is likely to be elevated. It is well established that loss of muscle mass and strength can be reversed with resistance training exercises, even into the seventh decade in older men (11) and frail elderly women (7). Moreover, evidence is available that demonstrates the hypertrophic effects of exercise on muscle, including at older ages (7, 11). It

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SARCOPENIA AND BODY WEIGHT 2. Baumgartner RN, Stauber PM, McHugh D, Koehler KM, and Garry PJ. Cross-sectional age differences in body composition in persons 60 years of age. J Gerontol A Biol Sci Med Sci 50: M307M316, 1995. 3. Borkan GA, Hults DE, Gerzof DE, Robbins AH, and Silbert CK. Age changes in body composition revealed by computed tomography. J Gerontol A Biol Sci Med Sci 38: 673677, 1983. 4. Chien S, Peng MT, Chen KP, Huang TF, Chang C, and Fang HS. Longitudinal studies on adipose tissue and its distribution in human subjects. J Appl Physiol 39: 825830, 1975. 5. Cohn SH, Vaswani AN, Yasumura S, Yeen K, and Ellis KJ. Assessment of cellular mass and lean body mass by noninvasive nuclear techniques. J Lab Clin Med 105: 305311, 1985. 6. Dutta C and Hadley EC. The signicance of sarcopenia in old age. J Gerontol 50A: 14, 1995. 7. Fiatarone MA, Marks EC, Ryan ND, Meredith CN, Lipsitz LA, and Evans WJ. High intensity strength training in nonagenarians. JAMA 263: 30293034, 1990. 8. Flynn MA, Nolph GB, Baker AS, Martin WM, and Krause G. Total body potassium in aging humans: a longitudinal study. Am J Clin Nutr 50: 713717, 1989. 9. Forbes GB. Human Body Composition. New York, NY: Springer Verlag, 1987 10. Forbes GB and Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 19: 653663, 1970. 11. Frontera WR, Meredith CN, OReilly KP, Knuttgen HG, and Evans WJ. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol 64: 10381044, 1988. 12. Gallagher D, Visser M, DeMeersman RE, Sepulveda D, Baumgartner RN, Pierson RN, Harris TB, and Heymseld SB. Appendicular skeletal muscle mass: effects of age, gender, and ethnicity. J Appl Physiol 83: 229239, 1997. 13. Gallagher D, Visser M, Sepulveda D, Pierson RN, Harris T, and Heymseld SB. How useful is body mass index for comparison of body fatness across age, gender, and ethnic groups? Am J Epidemiol 143: 228239, 1996. 14. Heymseld SB, Wang Z, Baumgartner RN, and Ross R. Human body composition: advances in models and methods. Annu Rev Nutr 17: 527558, 1997. 15. Langlois JA, Harris TB, Looker AC, and Madans J. Weight change between age 50 years and old age is associated with hip fracture in white women aged 67 years and older. Arch Intern Med 156: 989994, 1996. 16. Langlois JA, Visser M, Davidovic LS, Maggi S, Li G, and Harris TB. Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age. Arch Intern Med 158: 990996, 1998. 17. Lexell J. Human skeletal muscle undergoes major structural and functional changes with advancing age. J Nutr 127: 1011S 1013S, 1997. 18. Mller P, Alvestrand A, Bergstrm J, Furst P, and Hellstrm K. Electrolytes and free amino acids in leg skeletal muscle of young and elderly women. Gerontology 29: 18, 1983. 19. Moore FD, Olesen KH, McMurrey JD, Parker HV, Ball MR, and Boyden CM. The Body Cell Mass and Its Supporting Environment. Philadelphia, PA: Sanders, 1963. 20. Muller DC, Elahi D, Sorkin JD, and Andres R. Muscle mass: its measurement and inuence on aging. The Baltimore longitudinal study of aging. In: Nutritional Assessment of Elderly Populations. Measure and Function, edited by Rosenberg IH. New York, NY: Raven, 1995, p. 5062. 21. Najjar MF and Rowland M. Anthropometric reference data and prevalence of overweight, United States, 197680. In: Vital and Health Statistics. Washington, DC: US Govt. Printing Ofce, 1980, series II, no. 238. (DHHS publication 871688) 22. Noppa H, Andersson M, Bengtsson C, Bruce A, and Isaksson B. Longitudinal studies of anthropometric data and body composition. The population study of women in Goteborg, Sweden. Am J Clin Nutr 33: 155162, 1980. 23. Pierson RN, Lin DHY, and Phillips RA. Total body potassium in health: effects of age, sex, height, and fat. Am J Physiol 226: 206212, 1974.

may be necessary to advise elderly subjects to increase specic activities, focusing on resistance training for the maintenance of muscle mass and function. Study Limitations The current study population is limited in size and does not represent a random sample of older individuals but rather a convenience sample of healthy survivors. Moreover, we excluded subjects with large weight uctuations secondary to identiable mechanisms. As such, our ndings cannot be considered representative of the aging population in general. However, the unequivocal nding of an appendicular skeletal muscle mass loss over time in a healthy cohort suggests that the extent of muscle loss in a randomly selected sample would be greater than that observed in our study. It is possible that older adults who slightly decrease physical activity with age show small decreases in skeletal muscle mass and increases in body fat. A limitation of our study was the lack of information on daily physical activity at both measurement points, thereby preventing us from investigating if a portion of the individual variation in skeletal muscle loss was accounted for by variations in activity. Although the applied body composition methods were state of the art, our ability to accurately detect small compartmental changes over time was limited. Some of the observed changes in secondary variables (e.g., body cell mass) were only modestly greater than method measurement errors. Although our combined methods in a relatively large sample provide a clear and consistent pattern of group change in appendicular skeletal muscle and associated water and potassium over time (Table 4), results for individuals and sometimes specic methods were variable (e.g., fat-free mass was unchanged in women even though there was a signicant decrease in total body water). Improving body composition assessment method accuracy and reproducibility, particularly in light of the potential clinical applicability of these methods, is an important future goal. Based on our analysis of body composition changes in an elderly cohort living in New York City, using technologically advanced and multiple independent body composition methodologies, we present strong evidence of progressive skeletal muscle loss over a 5-yr observation period. These ndings extend earlier cross-sectional and limited longitudinal studies and lend support to the hypothesis that dynamic remodeling of soft tissues occurs even in healthy, ambulatory, weightstable elderly subjects.
This work was supported in part by National Institutes of Health Grants F32-AG-05679, R29-AG-14715, RO1-AG-13021, and P01-DK42618. REFERENCES 1. Abraham S, Johnson CL, and Najjar MF. Weight and height of adults 1874 years of age, United States, 19711974. In: Vital and Health Statistics. Washington, DC: US Govt. Printing Ofce, 1974, series II, no. 211. (DHEW publication 791659)

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