European Journal Clinical Nutrition (2001) 55, 663±672 ß 2001 Nature Publishing Group All rights reserved 0954±3007/01 $15.00 www.nature.com/ejcn ]> Original Communication Age-related differences in fat-free mass, skeletal muscle, body cell mass and fat mass between 18 and 94 years UG Kyle1, L Genton1, D Hans2, L Karsegard1, DO Slosman2 and C Pichard1* 1 Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland; and 2Nuclear Medicine, Geneva University Hospital, Geneva, Switzerland Objective: To determine (1) lean and fat body compartments, re¯ected by fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), body cell mass (BCM), total body potassium (TBK), fat mass and percentage fat mass, and their differences between age groups in healthy, physically active subjects from 18 to 94 y of age; and (2) if the rate of decrease in any one of the parameters by age might be accelerated compared to others. Methods: A total of 433 healthy ambulatory Caucasians (253 men and 180 women) aged 18 ± 94 y were measured by dual-energy X-ray absorptiometry (DXA) and whole body scintillation counter (TBK counter) using a large sodium iodide crystal (203 mm diameter). Results: The ASMM change (716.4 and 712.3% in men and women, respectively) in > 75 y-old compared to 18 to 34-y-old subjects was greater than the FFM change (711.8 and 79.7% in men and women, respectively) and this suggests that skeletal muscle mass decrease in older subjects was proportionally greater than non-skeletal muscle mass. BCM (725.1 and 723.2% in men and women, respectively) and TBK differences were greater than the differences in FFM or ASMM suggesting altered composition of FFM in older subjects. Women had lower peak FFM, ASMM, BCM and TBK than men. Conclusions: The decline in FFM, ASMM, BCM and TBK is accelerated in men and women after 60 y of age and FFM, ASMM, BCM and TBK are signi®cantly lower than in younger subjects. Fat mass continued to increase until around 75 y. Sponsorship: Foundation Nutrition 2000Plus, Geneva, Switzerland. Descriptors: dual energy X-ray absorptiometry (DXA); total body potassium (TBK); fat-free mass; appendicular skeletal muscle mass (ASMM); body cell mass (BCM); fat mass. European Journal of Clinical Nutrition (2001) 55, 663 ± 672 Introduction Signi®cant changes in body composition are known to occur with aging and are believed to be a consequence *Correspondence: C Pichard, Clinical Nutrition and Diet Therapy, Geneva University Hospital, 1211 Geneva, Switzerland. E-mail: [email protected] Contributors: UGK was mainly responsible for the original idea, and provided the ®nal data collection, executed the mathematical and statistical analysis, participated in designing the study and in the writing of the paper. LG and LK organized and coordinated the data collection of the research project, contributed to interpreting the data and the writing of the paper. DH and DOS participated in designing the study, analyzing the data and writing the paper. CP participated in developing the original idea, designing the study, analyzing the data and writing the paper. He also directed protocol execution, adherence and funding. Received 10 October 2000; revised 17 January 2001; accepted 18 January 2001 of imbalances between energy intake and energy needs associated with increasing sedentary lifestyle. In addition to progressive increases in fat mass with age, progressive reduction in fat-free mass (FFM) is also noted. Large absolute differences are known to exist between young and old subjects of similar body size in the individual compartments that compose the FFM (Mazariegos et al, 1994). Because weight and body mass index (BMI) alone are not adequate guides of underlying changes in FFM and fat mass during menopause (Heyms®eld et al, 1994) and aging in general (Guo et al, 1999), body composition should be measured in clinical management programs and epidemiological and clinical studies of aging (Guo et al, 1999). Body composition changes with aging are of interest because the age-related loss of muscle mass or `sarcopenia' is prevalent in the elderly and is strongly associated with impaired mobility, increased morbidity and mortality, and lower quality of life (Baumgartner et al, 1998; Kehayias et al, 1997; Roubenoff, 2000). Visser et al (1998) also found that Age-related differences in FFM UG Kyle et al 664 high body fat mass was an independent predictor of mobility-related disability in older men and women. High BMI, increased waist circumference and therefore high fat mass have also been associated with increased risk for cardiovascular disease and mortality (Allison et al, 1997; Heitmann et al, 2000). Recent advances in body composition measurements now allow the simultaneous measuring of fat and lean components and their regional distribution. Dual-energy X-ray absorptiometry (DXA) is being used to explore changes in regional fat and muscle mass. Recent studies (Heyms®eld et al, 1990; Jebb et al, 1993; Wang et al, 1996) support the validity of DXA-determined estimates of appendicular skeletal muscle mass (ASMM). In addition, whole body counting of potassium permits the evaluation of the quantitative relationship between body cell mass (BCM), and FFM and their changes during aging. Total body potassium (TBK) and BCM, the TBK-derived metabolically active portion of the FFM, are known to decrease with age. Low TBK values and TBK=FFM ratio indicate low BCM. However, BCM and FFM do not maintain a constant relationship to each other across heterogeneous populations (Gallagher et al, 1996). Thus de®cient BCM or TBK in older compared to younger subjects would also indicate de®cient muscle mass. A number of studies (Bartlett et al, 1991; Deurenberg et al, 1991; Gallagher et al, 1995, 1996; Guo et al, 1999) have evaluated associations between body composition parameters and age in healthy subjects. Nevertheless this is the ®rst study to evaluate lean body parameters (FFM, ASMM, BCM, TBK) and fat mass, derived from two independent methods, in 433 healthy subjects between 18 and 94 y and compared their differences between age groups and between genders. The purpose of this study was to (1) determine lean and fat body compartments re¯ected by FFM, ASMM, BCM, TBK, fat mass and percentage fat mass, and their differences between age groups in healthy, physically active subjects from 18 to 94 y of age; and (2) determine if the rate of change in any one the parameters might be greater than the change in other parameters. Table 1 Subjects and methods Subjects Four-hundred and thirty-three healthy ambulatory Caucasians (253 men and 180 women) aged 18 ± 94 y (Table 1) were included in this study. Subjects were non-randomly recruited through advertisement in local newspapers and invitations to participate in the study sent to members of elderly leisure clubs. Exclusion criteria were acute medical treatment or hospitalization within 3 months of measurement or physical handicap that might interfere with body composition measurement (amputation, paralysis, etc). Each subject was ®rst measured by DXA, then by TBK. All subjects signed an informed consent statement. The study protocol was approved by the Geneva University Hospital Ethics Committee. Body composition measurements Body height was measured to the nearest 0.5 cm and body weight was measured to the nearest 0.1 kg on a balance beam scale. Height and weight of both men and women were normally distributed. Fat-free mass and appendicular skeletal muscle mass. FFM was measured using whole-body DXA (Hologic QDR-45001 instrument, Enhanced Whole Body 8.26a software version; Hologic Inc. Waltham, MA, USA). The precision of the measurements is 1.0 and 2.0% for the FFM and FM, respectively (Mazess et al, 1990; Slosman et al, 1992). The effective total body radiation dose is 5.2 mSv (Blake et al, 1996; Lewis et al, 1994). Percentage of body fat was measured using the manufacturer's default de®nition. Trunk fat mass was determined by DXA as the total trunk region fat mass, excluding limb and head fat mass. ASMM was measured as the sum of the lean soft tissue masses for the arms and legs as described by Heyms®eld et al (1990). ASMM index, adjusted for differences in body Anthropometric characteristics of a healthy Caucasian population Age 18 ± 94 y Range 18 ± 34 y 35 ± 59 y 60 ± 74 y Men n Height (cm) Weight (kg) BMI (kg=m2) IBW (%) 253 175.3 7.7 77 9.8 25.1 2.8 109.4 12.1 (155 ± 199) (51.3 ± 106) (18.8 ± 32.3) (82 ± 140.9) 68 177.7 6.4 76.0 9.9 24.0 2.6 106.1 11.4 90 178.2 6.7 80.5 9.2* 25.4 2.8* 111.8 12.2* 47 171.6 6.4** 75.8 10.2* 25.8 3.2 111.3 13.7 48 170 8.4 72.9 8.3 25.2 2.5 107.7 9.9 Women n Height (cm) Weight (kg) BMI (kg=m2) IBW (%) 180 162.0 6.0 63.0 9.7 24.0 3.5 106.0 15.1 (147 ± 176) (41.8 ± 92.5) (17.5 ± 33.9) (76 ± 151) 40 166.2 4.9 61.4 6.4 22.2 2.1 99.5 9.2 35 163.8 5.2* 62.5 9 23.3 2.8 103.4 12.8 55 161.5 5.5* 66.2 11.4 25.3 4.0* 111.6 17.5* 50 158.0 5.2* 61.2 9.6* 24.5 3.5 106.8 15.5 BMI body mass index; IBW ideal body weight (Metropolitan Life Insurance, 1983). ANOVA comparison between adjacent age groups, *P < 0.05; **P < 0.001. European Journal of Clinical Nutrition > 75 y Age-related differences in FFM UG Kyle et al mass and skeletal size, was derived in the same fashion as BMI: ASMM index (kg=m2 ASMM (kg) divided by height (m) squared. Visser et al (1999) validated the Hologic QDR-4500 instrument in elderly subjects and found FFM was positively associated with FFM by four-compartment model (r2 0.98, s.e. of estimate 1.6 kg) and with computed tomography at all four leg regions (r2 0.86 ± 0.96). Total body potassium and body cell mass. The potassium40 body content was measured by using a whole body scintillation counter. Subjects were reclined in a tilting chair and were placed in the ®eld of view of a large sodium iodide crystal (203 mm diameter). The natural K-40 isotope exists at a known and constant natural abundance of 0.0012%. It was measured by counting the total pulses recorded in the channels of the photo peak of this isotope for 30 min. This technique in humans, at our institution, has an accuracy of 5% and a precision of 2% (Wenger & Soucas, 1964). Others reported a variability of potassium-40 counting in an anthropometric phantom is > 5% and in humans around 5% (Lukaski et al, 1981). BCM was calculated from TBK using the equation, BCM (kg) 0.00833 TBK (mmol) (Moore & Boyden, 1963). Physical activity In subjects > 60 y, physical activity was determined using a frequency questionnaire (Bernstein et al, 1999). The time spent on total physical activity was calculated by multiplying the frequency and duration of each activity in the previous week, summing the values across activities, and dividing by 7. Intensity scores, previously reported (Voorrips et al, 1991), were used to make the differences in energy expenditure of the various activities and sports activities comparable. The intensity scores are based on net energy cost of activities in mega joules per hour (Bink et al, 1966). Statistics Descriptive statistics were calculated for height, weight, percentage ideal body weight, BMI, FFM, ASMM, BCM, TBK, TBK=FFM ratio, fat mass and percentage fat mass, and are expressed as mean standard deviation (x s.d.) ANOVA was used to test for differences between age groups. Differences for body composition parameters for each age group compared to healthy young subjects (age 18 ± 34 y) were calculated as: percentage difference x 7 y=y 100, where x is FFM, BCM etc of each individual and y is the mean value for FFM, BCM etc of the 18 to 34-y-old men or women. Height-normalized FFM, ASMM, BCM, TBK, TBK=FFM ratio, fat mass and percentage fat mass were plotted against age to compare decreases in < 60 y com- pared to > 60-y-old subjects and determine if decreases with age in some parameters might be greater than decreases in others. The height was normalized to the median height of all men or women: 175 cm for men and 161.2 cm for women, respectively. Differences between two or more population regression coef®cients were tested as previously described (Zar et al, 1999). Statistical signi®cance was set at P 0.05 for all tests. 665 Results Table 1 shows the anthropometric characteristics of the healthy subjects between 18 and 94 y of age. Height was signi®cantly lower in 60 to 74-y-old than 35 to 59-y-old men and weight was highest in 35 to 59-y-old men. Height was signi®cantly lower in 60 to 74-y-old than 35 to 59-yold women and 35 to 59-y-old than 18 to 34-y-old women. Weight was highest in 60 to 74-y-old women and was signi®cantly lower in older age groups. Peak BMI and percentage ideal body weight were noted in 60 to 74-y-old for both genders and were lower in younger and older age groups. Fat-free mass and appendicular skeletal muscle mass FFM, ASMM and ASMM index peaked in men (Table 2, height adjusted Table 4) in 35 ± 59 y and were signi®cantly lower in older age groups. In women, FFM, ASMM and ASMM index (Table 3, height-adjusted, Table 4) were highest in the 18 to 34-y-olds and became gradually lower and were signi®cantly lower after 60 y of age compared to younger subjects. The FFM and ASMM changes as a percentage by which the parameters were lower than values in healthy men and women aged 18 ± 34 y are shown in Tables 2 and 3, respectively. The percentage change in ASMM was greater than the percentage change in FFM and this suggests that skeletal muscle was proportionally smaller than nonskeletal muscle mass in older men and women. The FFM (calculated from linear regressions in Figure 1) was 1.5 kg=decade lower in men and 0.8 kg=decade in women when reported as overall change and 1.7 kg=decade in men and 1.1 kg=decade noted in > 60 y women compared a 0.4 kg=decade in men and 0.3 kg=decade higher FFM in women < 60-y-old subjects. Similarly, the changes were much greater in > 60-y-old (71.0 kg=decade in men and 70.4 kg=decade in women) compared with stable ASMM in < 60-y-olds. Total body potassium and body cell mass BCM, TBK and TBK=FFM ratio were highest in the 18 to 34-y-olds, became gradually lower and were signi®cantly lower in > 60-y-old compared with younger men (Table 2, height adjusted Table 4) and women (Table 3, height European Journal of Clinical Nutrition Age-related differences in FFM UG Kyle et al 666 Table 2 Body composition changes with age in healthy men Age n Fat-free mass (kg) Da (%) ASMM (kg) Da (%) ASMM index (kg=m2) Da (%) Body cell mass (kg) Da (%) BCM=FFM (kg=kg) Total body potassium (g) Da (%) TBK=FFM (g=kg) Da (%) Fat mass (kg) Da (%) Fat mass (%) Da (%) 18 ± 94 y 18 ± 34 y 35 ± 59 y 60 ± 74 y < 75 y 253 60.4 6.6 68 62.3 6.1 25.8 3.6 27.2 3.0 8.38 0.85 8.59 0.76 31.5 5.2 34.8 3.8 0.52 0.05 147.8 24.2 0.56 0.04 163.4 17.9 2.44 0.25 2.63 0.20 16.7 5.4 14.0 4.8 21.4 5.3 18.1 4.9 90 63.3 5.6 70.7 8.8 27.5 3.0 0.5 10.9 8.66 0.82 0.7 9.5 34.0 3.5 71.1 10.3 0.54 0.04{ 159.7 16.6 71.1 10.3 2.53 0.16{ 72.1 6.3 17.3 5.3{ 11.7 34.2{ 21.2 4.9{ 8.5 24.8{ 47 57.3 5.5{ 78.3 9.0{ 23.8 2.7{ 12.1 10.6{ 8.10 0.82{ 75.8 9.6* 28.0 2.7{ 717.5 8.9{ 0.49 0.04{ 131.6 12.5{ 717.5 8.6{ 2.30 0.18{ 710.7 6.8{ 18.6 5.5 19.1 35.9 24.0 4.6{ 21.7 23.9* 48 55.1 6.0 712.4 9.5* 22.7 2.9 17.2 10.5* 7.84 0.75 78.8 8.7{ 25.4 3.6{ 726.3 10.5{ 0.46 0.04{ 119.2 17.0{ 726.3 10.5{ 2.16 0.18{ 716.2 7.0{ 17.6 4.7 13.7 30.2 24.0 4.9 22.9 25 ASMM appendicular skeletal muscle mass; TBK total body potassium; FFM fat-free mass. Percentage difference compared to 18 to 34-y-old group. ANOVA comparison between adjacent age groups (adjusted for height and weight), *P < 0.05; {P < 0.001. a adjusted Table 4), and were also signi®cantly lower in 35 to 59-y-old compared with 18 to 34-y-old woman. The TBK change was greater in men (78.7 g=decade) than in women (75.4 g=decade) and greater in > 60-y-old than < 60-yold men and women (Figure 2). The percentage change in TBK and BCM (Tables 2 and 3) was approximately twice the change in FFM and ASMM. The BCM=FFM ratio was also signi®cantly lower in older men and women. Thus it appears that the BCM and TBK changes are greater than changes in either FFM or ASMM. Women had lower peak FFM, ASMM, BCM and TBK than men. Table 3 Changes in body composition in > 60-y-old compared to < 60-y-old subjects Linear regressions for changes in height-adjusted body composition parameters for men and women, separated into < 60 and > 60 y, are shown in Figures 1 ± 3. The slopes of the regressions for FFM and ASMM (Figure 1) were non-signi®cantly positive in < 60-y-old men and women and signi®cantly negative in men > 60-y-old (FFM P 0.015; ASMM P 0.007) and non-signi®cantly negative in women. The change in FFM in > 60-y-old was greater in men than in women. Body composition changes with age in healthy women Age n Fat-free mass (kg) Da (%) ASMM (kg) Da (%) ASMM index (kg=m2) Da (%) Body cell mass (kg) Da (%) BCM=FFM (kg=kg) Total body potassium (g) Da (%) TBK=FFM (g=kg) Da (%) Fat mass (kg) Da (%) Fat mass (%) Da (%) 18 ± 94 y 18 ± 34 y 35 ± 59 y 60 ± 74 y > 75 y 180 42.8 4.6 40 45.0 3.6 17.2 2.3 18.5 1.9 6.55 0.68 6.71 0.58 20.8 3.5 24.1 2.5 0.49 0.06 97.7 16.4 0.54 0.04 113.3 11.6 2.28 0.26 2.52 0.21 20.7 7.2 17.3 5.8 31.6 6.6 26.9 4.6 35 44.4 4.2 70.4 9.3 18.0 2.2 71.8 11.9 6.69 0.65 70.1 9.6 22.6 2.6* 74.4 11.2* 0.51 0.04* 106.0 12.3* 74.5 11.1{ 2.39 0.19* 74.1 7.4* 18.6 5.6 8.2 32.5 29.0 5.2 6.8 19.3 55 42.5 4.6* 74.6 10.3* 16.9 2.2* 77.6 12.2* 6.47 0.69 73.4 10.3 19.9 2.7{ 715.5 11.4{ 0.47 0.05{ 93.4 12.7{ 15.9 11.4{ 2.19 0.21{ 712.1 8.4{ 24.1 8.4{ 40.3 48.9{ 34.9 6.6{ 28.6 24.5{ 50 40.2 4.2* 710.0 9.5* 16.0 2.1* 712.7 11.4* 6.40 0.74 74.4 11.0* 17.9 2.5{ 724.0 10.6{ 0.45 0.04* 84.2 11.7{ 24.2 10.5{ 2.10 0.20* 715.8 8.l{ 21.1 6.4* 22.8 37.1* 33.8 5.9 24.5 21.7 ASMM appendicular skeletal muscle mass; TBK total body potassium; FFM fat-free mass. Percentage difference compared to 18 to 34-y-old group. ANOVA comparison between adjacent age groups (adjusted for height and weight); *P < 0.05; {P < 0.001. a European Journal of Clinical Nutrition Age-related differences in FFM UG Kyle et al 667 Figure 1 Fat-free mass (FFM) (top) and appendicular skeletal muscle mass (ASMM) (bottom), normalized for height (men 175 cm, women 161.2 cm) vs age in 18 to 59-y-old (left) and 60 to 94-y-old (right) men and women. Table 4 Height-adjusteda body composition changes with age in healthy men and women Age 18 ± 94 y 18 ± 34 y 35 ± 59 y 60 ± 74 y > 75 y Men n Fat-free mass (kg) ASMM (kg) Body cell mass (kg) Total body potassium (g) TBK=FFM (g=kg) Fat mass (kg) 253 60.2 5.1 25.7 2.9 31.4 4.4 147.2 20.8 2.44 0.24 16.7 5.4 68 61.3 4.9 26.7 2.5 34.3 3.4 160.8 15.8 2.59 0.23 13.7 4.6 90 62.1 4.4 27.0 2.6 33.4 3.1 156.8 14.3 2.48 0.20{ 17.0 5.3{ 47 58.4 4.8{ 24.5 2.4{ 28.6 2.5{ 134.2 11.6{ 2.35 0.20{ 18.9 5.5* 48 56.6 4.4 23.3 2.3 26.1 3.l{ 122.5 14.5{ 2.23 0.21* 18.2 4.9 Women n Fat-free mass (kg) ASMM (kg) Body cell mass (kg) Total body potassium (g) TBK=FFM (g=kg) Fat mass (kg) 180 42.5 3.6 17.1 2.0 20.7 3.0 97.0 14.2 2.26 0.25 20.6 7.2 40 43.7 2.9 18.0 1.6 23.4 2.3 109.9 10.9 2.45 0.23 16.8 5.7 35 43.7 3.2 17.7 1.8 22.2 2.2* 104.2 10.5* 2.35 0.20 18.2 5.3 55 42.4 3.9 16.9 2.0* 19.9 2.4{ 93.0 11.1{ 2.18 0.21{ 24.0 8.3{ 50 40.9 3.6* 16.3 1.9 18.3 2.3{ 85.8 10.8{ 2.14 0.22 21.5 6.4 ASMM appendicular skeletal muscle mass; TBK total body potassium; FFM fat-free mass. Parameters normalized for median height in all subjects (175 cm for men, 161.2 cm for women). ANOVA comparison between adjacent age groups, *P < 0.05; {P < 0.001. a European Journal of Clinical Nutrition Age-related differences in FFM UG Kyle et al 668 Figure 2 Body cell mass (BCM) (top), and total body potassium (TBK) (middle), TBK=FFM ratio (bottom), normalized for height (men 175 cm, women 161.2 cm) vs age in 18 to 59-y-old (left) and 60 to 94-y-old (right) men and women. The BCM and TBK (Figure 2) were non-signi®cantly lower in men < 60 y, but signi®cantly (P 0.006) in women < 60 y and men and women > 60 y (P 0.001). TBK=FFM European Journal of Clinical Nutrition was signi®cantly lower in men and women < 60 y and > 60 y (P 0.010). The BCM, TBK and BCM=FFM ratio (not shown) decreases were greater in women than in men Age-related differences in FFM UG Kyle et al < 60 y and in men than in women > 60 y. The slopes of the regression for TBK=FFM ratio in younger and older subjects and BCM=FFM ratio in older subjects (data not shown) were similar in men and women. Signi®cant differences (P 0.001) existed between regression coef®cients between men and women and < 60 y and > 60-y-old for each parameter in Figures 1 ± 3, except for TBK=FFM ratio between men and women > 60 y and men and women < 60 y. Fat mass and percentage fat mass Both absolute and percentage fat mass were highest in 60 to 74-y-old men (Table 2, height adjusted Table 4) and women (Table 3, height adjusted Table 4) and remained stable thereafter, except for fat mass which was signi®cantly lower in > 75-y-old women. The percentage fat mass change was greatest in 60 to 74-y-old men and women and was greater in women than in men. Trunk fat mass was higher (P 0.0001) in 60 to 74-yold (9.8 3.5 kg) than in 18 to 34-y-old men (6.5 2.7 kg) and in 60 to 74 y (10.9 4.37 kg) than in 18 to 34-y-old (6.2 2.0 kg) women, and was lower thereafter (70.6 kg in men and 71.2 kg in women). The trunk fat mass, as a percentage of total fat mass, changed from 45.6 to 52.21% in youngest vs oldest men and from 36.7 to 45.2% in women. Appendicular (leg and arm) fat mass was also higher (7.7 2.3 kg) in 60 to 74-y-old compared to youngest (6.5 2.2 kg) men (P 0.016) and in women (12.0 4.0 kg compared to 9.6 2.4 kg respectively, P 0.005) and decreased thereafter (70.2 kg in men and 71.3 kg in women). Appendicular fat mass as a percentage of total fat mass was lower (P 0.0001) in older (42.2%) compared to youngest men (46.9%) and older (50.8%) compared to youngest (57.3%) women and remained stable after 75 y. Fat mass and percentage fat mass (Figure 3) became signi®cantly higher (P 0.02) in men and women < 60 y and remained stable > 60 y in men and women. Discussion The loss of FFM and muscle mass and increased fat mass with aging has been documented in a number of studies using a variety of methods and it appears to occur even in relatively healthy elderly persons (Baumgartner et al, 1995; Gallagher et al, 1995). This is the ®rst study to evaluate lean body parameters (FFM, ASMM, BCM, TBK) and fat mass, derived from two independent methods, in 433 healthy subjects between 18 and 94 y and compare their differences between age groups and between genders. The results show that the parameters re¯ecting lean body mass changed at a faster rate after 60 y of age in both men and women and were signi®cantly lower in older men and women. Fat-free mass and appendicular skeletal muscle mass 669 Our study shows that the height-adjusted FFM and ASMM remained stable until 60 y of age but that there was an accelerated change in FFM and ASMM after 60 y. Our results agree with Kehayias et al (1997), who reported a decrease in TBK between 20 and 90 y and an accelerated loss in older subjects. The relatively stable FFM seen until 60 y in this study has been reported by others (Chumlea et al, 1999; Pichard et al, 2000). In a comparison between a small number of younger (n 19, 29.9 4.4 y) and older women (74.2 6.7 y), Mazariegos et al (1994) found lower FFM, ASMM and BCM in weight-matched older women. The FFM and ASMM change in our study was greater in men than in women, con®rming results by others (Gallagher et al, 1995). Gallagher reported linear decreases in ASMM between 20 and 90 y and suggested that a nonlinear decrease was not found in their subjects due to limited inclusion of very old subjects. However, the accelerated changes noted in FFM and ASMM after 60 y has not been previously reported, primarily because few studies (Gallagher et al, 1995; Starling et al, 1999) have investigated ASMM across the age span of 20 ± 94 y. The greater percentage decrease in ASMM than in FFM would suggest that the loss of skeletal muscle mass is greater than loss of non-skeletal muscle mass, and this is con®rmed by the ASMM index which indicates loss of muscle mass after controlling for body mass. These results agree with Cohn et al (1985) who reported a greater decrease with age in muscle than non-muscle lean (organ) mass and TBK. Total body potassium and body cell mass BCM and TBK (Table 2 and Figure 2) changes were found to be greater than the changes in FFM and ASMM and greater in > 60 y than < 60 y men and women. TBK and BCM were approximately 25% lower in oldest than youngest men and women. The results of this study also indicate that BCM and FFM do not maintain a constant relationship to each other with aging. This is con®rmed by the signi®cantly lower BCM=FFM ratio and lower TBK=FFM ratio with age. These ®ndings agree with those from other studies (Cohn et al, 1985) reporting a greater change with age in TBK than FFM. Mazariegos et al (1994) postulated that the lower FFMto-protein ratio found in their older women was possibly due to a relative increase in connective tissue=structural protein with age, which would explain the lower decrease in ASMM than BCM. They found inconsistent differences between three markers of skeletal muscle: TBK, ASMM and cross-sectional limb muscle area by anthropometrics. As in our study, they found ASMM to be 11% and TBKdetermined BCM 17% lower in older women. Our study European Journal of Clinical Nutrition Age-related differences in FFM UG Kyle et al 670 Figure 3 Fat mass (top) and percentage fat mass (bottom), normalized for height (men 175 cm, women 161.2 cm) vs age in 18 to 59-y-old (left) and 60 to 94-y-old (right) men and women. also found similarly lower ASMM and BCM in men. They suggested that skeletal muscles atrophy with increasing age and that the atrophied muscle is characterized by loss of myo®brils and associated loss of potassium and increased extracellular ¯uids, connective tissue and fat (Lowry & Hastings, 1942). The replacement of cell mass by collagen and the relative expansion of extracellular ¯uid in elderly subjects would explain the lower changes in ASMM than in BCM. Baumgartner et al (1995) suggested that the active cell mass may be replaced to a greater extent in women than in men, but had no explanation for this apparent sex difference. Lexell et al (1983) found 18% smaller muscle size and 25% fewer number of muscle cells at autopsy in elderly men (70 ± 73 y) than in young men (19 ± 37 y), which is close to the 16% lower ASMM and 25% lower BCM noted in this study. Thus sarcopenia in elderly subjects may be due to muscle atrophy due to a gradual and selective loss of European Journal of Clinical Nutrition cell mass, and a decrease in number and size of muscle ®bres (Lexell et al, 1995). The results of this study show that ASMM and BCM appear to parallel the gradual loss of cell mass and muscle ®bre loss noted with increasing age. Fat-free mass and physical activity Results from a physical activity questionnaire completed by all > 69-y-old subjects in our study, results reported elsewhere (Kyle et al, 2001) revealed no physical limitations or restrictions in mobility in the older subjects in this study. The lower FFM, ASMM and ASMM index noted in our older subjects did not appear to cause physical disability or loss of functioning, since all of the subjects were fully independent, without limitations in mobility and reported relative high physical activity levels (men 202 108 min=day, women 222 98 min=day, and < 20.9% of men and < 15% of women reported < 120 min=day of Age-related differences in FFM UG Kyle et al physical activity). Thus FFM, ASMM and BCM appear to decrease as part of normal aging and in spite of considerable activity reported by the older adults in this study. Activities reported were predominantly walking, general household and gardening activities which are not generally considered `body building or strength activities' and thus would not necessarily have prevented muscle wasting, but would have contributed to maintenance of body weight. Visser et al (1998) did not ®nd that low skeletal mass was associated with self-reported disability. However, they could not rule out that persons with low skeletal muscle mass dropped out earlier in the study. Further research should be directed at determining the threshold of FFM and ASMM necessary for normal physical functioning. Fat mass Our results show that fat mass accumulates with age in men and women until 74 y and decreases slightly thereafter in women. These ®ndings agree with Bartlett et al (1991), Pichard et al (2000) and Kyle et al (2001) who found that fat mass increased beyond middle age, but contradicts ®ndings by a previous report (Chumlea et al, 1998) that there is little or no further gain in fat mass during old age. In addition, our data con®rms previous reports (Baumgartner et al, 1995) that fat mass, in terms of percentage fat mass, may be relatively stable in elderly men but may decrease with age in elderly women. Fat mass gain was lower in our subjects < 60 y (0.21 kg=y in men and 0.14 kg=y in women) compared to 0.37 kg=y and 0.41 kg=y reported by Guo et al (1999) in men and women, respectively, and may be explained by lower rates of weight gain with age in our subjects, Percentage fat mass was lower in our subjects than in subjects with higher weights reported by Cohn et al, (1985). We found trunk and appendicular fat mass became progressively higher until 60 ± 74 y, where peak fat mass was noted in men and women and was lower thereafter. Our results contradict Baumgartner et al (1995) who suggested that the accumulation of abdominal and visceral fat that has been observed in both men and women with age occurs primarily during middle age and there may be little or no further increase during old age. Longitudinal studies need to con®rm this observation. Visser et al (1998) found high levels of disability in subjects with high fat mass (> 32.0% and 43.7% in men and women, respectively). Less than 2.8% of our subjects exceeded these levels of fat mass. This study neither con®rms nor contradicts ®ndings that high fat mass leads to increased disability. Waist circumference strongly predicted death from cardiovascular disease in older men (Allison et al, 1997; Heitmann et al, 2000). We are unable to determine whether the age-related increase in trunk fat mass affects cardiovascular risk. The greater fat mass observed in the elderly subjects in spite of only slightly higher BMIs suggests that the proportion of mass at a given BMI is different in young and old. These ®ndings give further evidence of the limitation of using BMI as an indicator of fatness or leanness. Individual body composition compartments, ie FFM and fat mass, should, therefore, be measured to evaluate changes in body composition with aging. This is especially important in subjects in whom an increased fat mass might mask decreases in FFM that might not be observed when assessment is limited to determining BMI only. 671 Limitations of study The subjects in this study were not randomly selected. However, the BMI in our study was similar to a randomly sampled Swiss population (Euralim Study, a European public health study of eating habits and cardiovascular disease and cancer risk factors; Morabia et al, 1997). The subjects in this study were volunteers in good health, and may not be representative of the general population, especially in the > 60 y groups. The absence of mobility problems and the relative high prevalence of regular physical activity appears to have aided in maintaining functional functioning and may have limited the loss of FFM and ASMM. The accuracy and precision of DXA is known to depend in part on the thickness of the X-ray absorber. The extent to which beam hardening or insuf®cient X-ray attenuation may affect the accuracy of whole body and body segment estimates of the lean tissue is not well established. DXAmeasured ASMM includes non-muscle fat-free components, such as skin, connective tissue and non-lipid portions of adipose tissue, but their amounts are likely to be small relative to ASMM (Gallagher et al, 1995). This study did not measure total body water compartment and their in¯uence on FFM composition with age, but this should be further explored. Conclusion This is the ®rst study to evaluate lean body parameters (FFM, ASMM, BCM, TBK) and fat mass, derived from two independent methods, in 433 healthy subjects between 18 and 94 y. The decline in FFM, ASMM, BCM and TBK is accelerated in men and women after 60 y of age and FFM, ASMM, BCM and TBK are signi®cantly lower than in younger subjects. Fat mass continued to increase until around 75 y. 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