The mechanism(s) governing the gain of upper-body fat and its relationship to the decrease in bone mass with age is still unclear. Therefore, four groups of subjects matched for weight, height, and body mass index (n = 119; 60 women, 59 men), but differing in age (above and below 50 y) and sex were investigated using dual energy x-ray absorptiometry (DXA) to assess body composition (bone, lean, and fat mass as well as its distribution) and indirect calorimetry to determine resting fuel metabolism. Fat mass of trunk and arms (P < 0.01), but not legs, increased with advancing age in males, resulting in a continuous increase in the ratio of upper- to lower-body fat (r = 0.45, P < 0.001). In contrast, total fat mass remained stable in women, irrespective of menopause, but a redistribution of fat occurred with advancing age (r = 0.43, P < 0.001), resulting in a higher upper- to lower-body fat ratio (P < 0.05) in older than in younger women. Total lean soft-tissue mass of all segments of the body was greater in men than in women irrespective of age (P < 0.001), and lower in the older groups than in the younger ones irrespective of sex. In males, but not females, lean soft-tissue mass in arms and legs decreased (r = 0.57, P < 0.001), whereas the ratio of total fat to lean soft-tissue mass increased (r = 0.53, P < 0.001) with age. Bone mineral content correlated with total body fat in both groups of women and in young males (r > 0.5, P < 0.001), but not in older males. With advancing age, the proportion of lean soft-tissue mass occupied by total skeleton declined in women (n = 59, P < 0.001), but remained stable in males. Resting energy expenditure decreased with age in both sexes. Protein and carbohydrate oxidation were similar in all four groups of subjects. Total fat oxidation and fat oxidation per kilogram of lean soft-tissue mass decreased with age (r > 0.36, P < 0.01) in males, but not in females, whereas it increased with increasing fat mass in females (r > 0.32, P < 0.03), but not in males. In contrast, fat oxidation per kilogram of fat mass decreased with fat mass in males (r = 0.61, P < 0.001), but not in females. Our results suggest that aging affects body composition and fuel metabolism differently in each gender, leading to reduced fat oxidation and accumulation of upper-body fat with loss of striated muscle in men, and to an increased ratio of upper- to lower-body fat and bone loss in women, the latter depending on fat mass.