Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis.

Creatine monohydrate (CrM) supplementation during resistance exercise training results in a greater increase in strength and fat-free mass than placebo. Whether this is solely due to an increase in intracellular water or whether there may be alterations in protein turnover is not clear at this point. We examined the effects of CrM supplementation on indexes of protein metabolism in young healthy men (n = 13) and women (n = 14). Subjects were randomly allocated to CrM (20 g/day for 5 days followed by 5 g/day for 3-4 days) or placebo (glucose polymers) and tested before and after the supplementation period under rigorous dietary and exercise controls. Muscle phosphocreatine, creatine, and total creatine were measured before and after supplementation. A primed-continuous intravenous infusion of L-[1-(13)C]leucine and mass spectrometry were used to measure mixed-muscle protein fractional synthetic rate and indexes of whole body leucine metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine rate of appearance. CrM supplementation increased muscle total creatine (+13.1%, P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09). CrM supplementation did not increase muscle fractional synthetic rate but reduced leucine oxidation (-19.6%) and plasma leucine rate of appearance (-7.5%, P < 0.05) in men, but not in women. CrM did not increase total body mass or fat-free mass. We conclude that short-term CrM supplementation may have anticatabolic actions in some proteins (in men), but CrM does not increase whole body or mixed-muscle protein synthesis.     

Size at birth, fat-free mass and resting metabolic rate in adult life.

Resting metabolic rate is an important predictor of obesity and is closely related to fat-free mass. There is evidence that fat-free mass may be partly determined during critical periods of growth before and after birth. The objective of this study was to examine the relationship between size at birth, childhood growth and fat-free mass and resting metabolic rate in adult life. 318 men and women with detailed records of body size at birth and growth during school years participated in the study. Fat-free mass correlated positively with birth weight among both sexes (r = 0.264, p < 0.001). Those having a higher birth weight had a higher fat-free mass at any adult BMI. Fat-free mass among men increased by 2.2 kg (95 % Cl 0.5 to 3.9; p = 0.01) for every kg increase in birth weight and by 1.5 kg (95 % Cl 1.3 to 1.7, p < 0.0001) for every kg/m(2) BMI in adult life. In women, fat-free mass increased by 2.7 kg (95 % Cl 1.6 - 3.9; p < 0.001) for every kg increase in birth weight and by 0.8 kg (95 % CI 0.7 to 1.0, p < 0.001) for every kg/m(2) of BMI in adult life. Height, weight and body mass index at each age from 7 to 15 years were also strongly, positively associated with fat-free mass. A negative correlation between birth weight and resting metabolic rate expressed per unit of fat-free mass (r = - 0.158; p < 0.001) was found. Fat-free mass may be determined during critical periods of muscle growth in utero and during childhood. The muscle tissue of people who had a lower birth weight is more metabolically active than those with a higher birth weight. This may protect them from the increased risk of obesity associated with low fat-free mass.     

Ovarian suppression with gonadotropin-releasing hormone agonist reduces whole body protein turnover in women

The age-related decline in fat-free mass is accelerated in women after menopause. The role of ovarian hormone deficiency in the regulation of fat-free mass, however, has not been clearly defined. To address this question, we examined the effect of ovarian hormone suppression on whole body protein metabolism. Whole body protein breakdown, oxidation, and synthesis were measured using [(13)C]leucine in young, healthy women with regular menstrual patterns before and after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n = 6) or placebo (n = 7). Protein metabolism was measured under postabsorptive and euglycemic-hyperinsulinemic-hyperaminoacidemic conditions. Ovarian suppression did not alter whole body or regional fat-free mass or adiposity. In the postabsorptive state, GnRHa administration was associated with reductions in protein breakdown and synthesis (P < 0.05), whereas no change in protein oxidation was noted. Under euglycemic-hyperinsulinemic-hyperaminoacidemic conditions, a similar reduction (P < 0.05) in protein synthesis and breakdown was noted, whereas, protein oxidation increased (P < 0.05) in the placebo group. Testosterone, steroid hormone precursors, insulin-like growth factor I, and their respective binding proteins were not altered by GnRHa administration, and changes in these hormones over time were not associated with GnRHa-induced alterations in protein metabolism, suggesting that changes in protein turnover are not due to an effect of ovarian suppression on other endocrine systems. Our findings provide evidence that endogenous ovarian hormones participate in the regulation of protein turnover in women.     

Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [(13)C]leucine in healthy premenopausal (n = 15, 49 +/- 1 yr) and postmenopausal (n = 18, 53 +/- 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [(13)C]leucine and [(2)H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo (n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.     

One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women.

Changing body composition has been suggested as a pathway to explain age-related functional decline. No data are available on the expected changes in body composition as measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of older persons. Body composition data at baseline, 1-yr follow-up, and 2-yr follow-up was measured by DXA in 2,040 well-functioning black and white men and women aged 70-79 yr, participants of the Health, Aging, and Body Composition Study. After 2 yr, a small decline in total body mass was observed (men: -0.3%, women: -0.4%). Among men, fat-free mass and appendicular lean soft tissue mass (ALST) decreased by -1.1 and -0.8%, respectively, which was masked by a simultaneous increase in total fat mass (+2.0%). Among women, a decline in fat-free mass was observed after 2 yr only (-0.6%) with no change in ALST and body fat mass. After 2 yr, the decline in ALST was greater in blacks than whites. Change in total body mass was associated with change in ALST (r = +0.58 to +0.70; P < 0.0001). Among participants who lost total body mass, men lost relatively more ALST than women, and blacks lost relatively more ALST than whites. In conclusion, the mean change in body composition after a 1- to 2-yr follow-up was 1-2% with a high interindividual variability. Loss of ALST was greater in men compared with women, and greater in blacks compared with whites, suggesting that men and blacks may be more prone to muscle loss.     

Role of muscle loss in the age-associated reduction in VO2 max

A progressive decline in maximal O2 consumption (VO2max) expressed traditionally as per kilogram body weight generally occurs with advancing age. To investigate the extent to which this decline could be attributable to the age-associated loss of metabolically active tissue, i.e., muscle, we measured 24-h urinary creatinine excretion, an index of muscle mass, in 184 healthy nonobese volunteers, ages 22-87 yr, from the Baltimore Longitudinal Study of Aging who had achieved a true VO2max during graded treadmill exercise. A positive correlation was found between VO2max and creatinine excretion in both men (r = 0.64, P less than 0.001) and women (r = 0.47, P less than 0.001). As anticipated, VO2max showed a strong negative linear relationship with age in both men and women. Creatinine excretion also declined with age in men and women. When VO2max was normalized for creatinine excretion, the variance in the VO2max decline attributable to age declined from 60 to 14% in men and from 50 to 8% in women. Thus comparing the standard age regression of VO2max per kilogram body weight with that in which VO2max is normalized per milligram creatinine excretion, the decline in VO2max between a hypothetical 30 yr old and a 70 yr old was reduced from 39 to 18% in men and from 30 to 14% in women. We conclude that in both sexes, a large portion of the age-associated decline in VO2max in non-endurance-trained individuals is explicable by the loss of muscle mass, which is observed with advancing age.     

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.     

Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.

We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.     

Reducing plasma HIV RNA improves muscle amino acid metabolism

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577-E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (> or =1 log) increased muscle protein synthesis rate and reduced R(a) Gln and muscle proteasome activity in 10 men and 1 woman (22-57 yr, 60-108 kg, 17-33 kg muscle) with advanced HIV (CD4 = 0-311 cells/microl; HIV RNA = 10-375 x 10(3) copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/microl, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 +/- 0.005 vs. 0.078 +/- 0.006%/h, P = 0.01), Ra Gln decreased (387 +/- 33 vs. 323 +/- 15 micromol.kg fat-free mass(-1).h(-1), P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% (P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, approximately 3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.     

Exercise and nutritional needs of elderly people: effects on muscle and bone

Advancing age is associated with a remarkable number of changes in body composition. Reductions in lean body mass have been well characterized. This decreased lean body mass occurs primarily as a result of losses in skeletal muscle mass^{1, 2}. This age-related loss in muscle mass has been termed sarcopenial³. Loss in muscle mass accounts for the age-associated decreases in basal metabolic rate, muscle strength, and activity levels, which, in turn is the cause of the decreased energy requirements of the elderly. In sedentary individuals, the main determinant of energy expenditure is fat-free mass, which declines by about 15% between the third and eighth decade of life. It also appears that declining caloric needs are not matched by an appropriate decline in caloric intake, with the ultimate result an increased body fat content with advancing age. Increased body fatness along with increased abdominal obesity are thought to be directly linked to the greatly increased incidence of Type II diabetes among the elderly. This review will discuss the extent to which regularly performed exercise can effect nutritional needs and functional capacity in the elderly. In addition, some basic guidelines for beginning an exercise program for older men and women, and establishing community-based programs are provided.     

Effects of dietary protein content on IGF-I, testosterone, and body composition during 8 days of severe energy deficit and arduous physical activity.

Energy restriction coupled with high energy expenditure from arduous work is associated with an altered insulin-like growth factor-I (IGF-I) system and androgens that are coincident with losses of fat-free mass. The aim of this study was to determine the effects of two levels of dietary protein content and its effects on IGF-I, androgens, and losses of fat-free mass accompanying energy deficit. We hypothesized that higher dietary protein content would attenuate the decline of anabolic hormones and, thus, prevent losses of fat-free mass. Thirty-four men [24 (SD 0.3) yr, 180.1 (SD 1.1) cm, and 83.0 (SD 1.4) kg] participated in an 8-day military exercise characterized by high energy expenditure (16.5 MJ/day), low energy intake (6.5 MJ/day), and sleep deprivation (4 h/24 h) and were randomly divided into two dietary groups: 0.9 and 0.5 g/kg dietary protein intake. IGF-I system analytes, androgens, and body composition were assessed before and on days 4 and 8 of the intervention. Total, free, and nonternary IGF-I and testosterone declined 50%, 64%, 55%, and 45%, respectively, with similar reductions in both groups. There was, however, a diet x time interaction on day 8 for total IGF-I and sex hormone-binding globulin. Decreases in body mass (3.2 kg), fat-free mass (1.2 kg), fat mass (2.0 kg), and percent body fat (1.5%) were similar in both groups (P = 0.01). Dietary protein content of 0.5 and 0.9 g/kg minimally attenuated the decline of IGF-I, the androgenic system, and fat-free mass during 8 days of negative energy balance associated with high energy expenditure and low energy intake.     

Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting.

Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 x 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass (r = -0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area (P = 0.02). Testosterone (P = 0.03) and training (P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness.     

Age and regional specificity of peak limb vascular conductance in men.

Because of methodological variation in previous studies, age-associated changes in peak limb vascular conductance (VC(peak); a functional index of arterial structure) and its determinants remain poorly defined. The objectives of this study were to describe and compare age-associated changes in peak forearm and calf conductance across a broad age range and to identify physiological characteristics that are predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/brachial mean arterial pressure) of the forearm (forearm VC(peak)) and calf (calf VC(peak)) after 10 min of arterial occlusion was measured twice in 68 healthy, normally active men aged 20-79 yr. Aerobic capacity (cycle peak oxygen consumption), arterial health (ankle-brachial index, pulse wave velocity), and limb-specific measures of muscle mass (dual-energy X-ray absorptiometry) and isometric strength (grip, plantar flexion) were also assessed. The relative decline in forearm VC(peak) with age (-6.6% per decade; P < 0.001) was greater than the decline in calf VC(peak) (-3.4% per decade; P = 0.004). Limb VC(peak) per kilogram of muscle declined with age in the forearm (-3.8% per decade; P = 0.004) but not in the calf (P = 0.35). Age, Vo(2 peak), and regional muscle mass were significant predictors of peak conductance in both limbs; however, these predictors explained considerably less variance in the calf than in the forearm. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in men, but the magnitude of this effect is reduced in the calf relative to the forearm. This could reflect regional differences in habitual muscle use with aging in normally active men.     

Changes in maximal aerobic capacity with age in endurance-trained women: 7-yr follow-up.

On the basis of cross-sectional data, we previously reported that the absolute, but not the relative (%), rate of decline in maximal oxygen consumption (VO(2 max)) with age is greater in endurance-trained compared with healthy sedentary women. We tested this hypothesis by using a longitudinal approach. Eight sedentary (63 +/- 2 yr at follow-up) and 16 endurance-trained (57 +/- 2) women were reevaluated after a mean follow-up period of 7 yr. At baseline, VO(2 max) was ~70% higher in endurance-trained women (48.1 +/- 1.7 vs. 28.1 +/- 0.8 ml. kg(-1). min(-1). yr(-1)). At follow-up, body mass, fat-free mass, maximal respiratory exchange ratio, and maximal rating of perceived exertion were not different from baseline in either group. The absolute rate of decline in VO(2 max) was twice as great (P < 0.01) in the endurance-trained (-0.84 +/- 0.15 ml. kg(-1). min(-1). yr(-1)) vs. sedentary (-0.40 +/- 0.12 ml. kg(-1). min(-1). yr(-1)) group, but the relative rates of decline were not different (-1.8 +/- 0.3 vs. -1.5 +/- 0.4% per year). Differences in rates of decline in VO(2 max) were not related to changes in body mass or maximal heart rate. However, among endurance-trained women, the relative rate of decline in VO(2 max) was positively related to reductions in training volume (r = 0.63). Consistent with this, the age-related reduction in VO(2 max) in a subgroup of endurance-trained women who maintained or increased training volume was not different from that of sedentary women. These longitudinal data indicate that the greater decrease in maximal aerobic capacity with advancing age observed in middle-aged and older endurance-trained women in general compared with their sedentary peers is due to declines in habitual exercise in some endurance-trained women. Endurance-trained women who maintain or increase training volume demonstrated age-associated declines in maximal aerobic capacity not different from healthy sedentary women.     

Resistance training increases basal limb blood flow and vascular conductance in aging humans.

Age-related reductions in basal limb blood flow and vascular conductance are associated with the metabolic syndrome, functional impairments, and osteoporosis. We tested the hypothesis that a strength training program would increase basal femoral blood flow in aging adults. Twenty-six sedentary but healthy middle-aged and older subjects were randomly assigned to either a whole body strength training intervention group (52 +/- 2 yr, 3 men, 10 women) who underwent three supervised resistance training sessions per week for 13 wk or a control group (53 +/- 2 yr, 4 men, 9 women) who participated in a supervised stretching program. At baseline, there were no significant differences in blood pressure, cardiac output, basal femoral blood flow (via Doppler ultrasound), vascular conductance, and vascular resistance between the two groups. The strength training group increased maximal strength in all the major muscle groups tested (P < 0.05). Whole body lean body mass increased (P < 0.05) with strength training, but leg fat-free mass did not. Basal femoral blood flow and vascular conductance increased by 55-60% after strength training (both P < 0.05). No such changes were observed in the control group. In both groups, there were no significant changes in brachial blood pressure, plasma endothelin-1 and angiotensin II concentrations, femoral artery wall thickness, cardiac output, and systemic vascular resistance. Our results indicate that short-term strength training increases basal femoral blood flow and vascular conductance in healthy middle-aged and older adults.     

Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat.

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 +/- 1 yr, body mass index = 33.2 +/- 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 +/- 0.8 vs. 24.3 +/- 1.0 ml.kg(-1).min(-1), P < 0.0001), decreased body weight (P < 0.0001) and fat mass (P < 0.001), while fat-free mass was not altered (P > 0.05). VF (176 +/- 20 vs. 136 +/- 17 cm2, P < 0.0001), subcutaneous fat (351 +/- 34 vs. 305 +/- 28 cm2, P < 0.03), and total abdominal fat (525 +/- 40 vs. 443 +/- 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower (P < 0.003) after training, but total adiponectin and tumor necrosis factor-alpha remained unchanged. Insulin resistance was reversed by exercise (40.1 +/- 7.7 vs. 27.6 +/- 5.6 units, P < 0.01) and correlated with changes in VF (r = 0.66, P < 0.01) and maximal oxygen consumption (r = -0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.     

Weight stability masks sarcopenia in elderly men and women

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 nonsignificantly 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.     

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults.

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.