Age-related loss of muscle protein may involve a decreased response to anabolic factors of muscle protein synthesis through dysregulation of translation factors. To verify this hypothesis, we simultaneously investigated muscle protein synthesis and expression of some factors implicated in insulin signal transduction during hyperinsulinemia and hyperaminoacidemia in 6 young (25+/-1 year; mean+/-sem) and 8 elderly subjects (72+/-2 year). Incorporation of L-[1-13C] leucine in muscle proteins (fractional synthesis rate, FSR) was measured in vastus lateralis, before and during a euglycemic hyperinsulinemic hyperaminoacidemic clamp, together with Western blot analysis of protein kinase B (PKB), mTOR, 4E-BP1, and S6K1 phosphorylation. In basal state, muscle protein FSR was reduced in elderly in comparison with young subjects (0.061+/-0.004% per hour) vs 0.082+/-0.010% per hour, elderly vs. young, P<0.05). During clamp, muscle protein FSR was stimulated in young (0.119+/-0.006% per hour; P<0.05), but this response was significantly lower in elderly subjects (0.084+/-0.005% per hour, P<0.05 vs young subjects). Phosphorylation of PKB, mTOR, and 4E-BP1 were similarly increased by insulin and amino acid in both groups, except for S6K1 phosphorylation, which was not stimulated in elderly subjects. In conclusion, 1) response of muscle protein synthesis to insulin and amino acid is impaired in elderly humans; 2) a defect in S6K1 pathway activation may be responsible for this alteration. This modification is a mechanistic basis of sarcopenia development during aging.

The present study was designed to assess the effects of dietary leucine supplementation on muscle protein synthesis and whole body protein kinetics in elderly individuals. Twenty healthy male subjects (70 ± 1 years) were studied before and after continuous ingestion of a complete balanced diet supplemented or not with leucine. A primed (3.6 μmol kg −1 ) constant infusion (0.06 μmol kgphenylalanine was used to determine whole body phenylalanine kinetics as well as fractional synthesis rate (FSR) in the myofibrillar fraction of muscle proteins from vastus lateralis biopsies. Whole body protein kinetics were not affected by leucine supplementation. In contrast, muscle FSR, measured over the 5-h period of feeding, was significantly greater in the volunteers given the leucine-supplemented meals compared with the control group (0.083 ± 0.008 versus 0.053 ± 0.009% h −1 , respectively, P < 0.05). This effect was due only to increased leucine availability because only plasma free leucine concentration significantly differed between the control and leucine-supplemented groups. We conclude that leucine supplementation during feeding improves muscle protein synthesis in the elderly independently of an overall increase of other amino acids. Whether increasing leucine intake in old people may limit muscle protein loss during ageing remains to be determined.

Chronic bilateral subthalamic stimulation leads to a spectacular clinical improvement in patients with motor complications. However, the post-operative body weight gain involved may limit the benefits of surgery and induce critical metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined 1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC) with rigorous control of food intakes and activities [sleep metabolic rate, resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13 km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation (M + 3). Before surgery, EE was compared between the Parkinsonian patients and healthy subjects matched for height and body composition (metabolic rate during sleep, daily EE) or matched to predicted values (basal metabolic rate). Before surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2 +/- 2.3%, respectively, P < 0.05) and (2) basal metabolic rate (L-dopa 'on') was higher than predicted basal metabolic rate (+11.5 +/- 4.0%, P < 0.05) but was further increased without L-dopa (+8.4 +/- 3.2% vs L-dopa 'on', P < 0.05). EE during daily activities was higher during 'off' periods compared to 'on' periods for both men (+19.3 +/- 3.3%, P < 0.0001) and women (+16.1 +/- 4.7%, P < 0.01). After surgery, there was a 3.4 +/- 0.6 kg (P < 0.0001) body weight increase together with fat mass (P < 0.0001) and fat-free mass (P < 0.05) in Parkinsonian men and a 2.6 +/- 0.8 kg (P < 0.05) body weight increase together with fat mass (P < 0.05) in Parkinsonian women. Sleep metabolic rate increased in men (+7.5 +/- 2.0%, P < 0.01) to reach control values but remained unchanged in women. Daily EE decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%, respectively, P < 0.01) but there was no correlation between daily EE changes and body weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.