Influence of adiposity in the blunted whole-body protein anabolic response to insulin with aging

Background. Although insulin resistance of glucose is often reported with aging. that of protein metabolism is still debated. We tested if the insulin sensitivity of protein metabolism parallels that of glucose and is altered with aging. Methods. Whole-body C-13-leucine and H-3-glucose kinetics were measured in the postabsorptive state and during an hyperinsulinemic, euglycemic, isoaminoacidemic clamp in 12 young men (age: 27 +/- 1 years; body mass index [BMI]: 23 +/- 1 kg/m(2)). 11 young women (age: 25 +/- 1 years; BMI: 21 +/- 1 kg/m(2)), 9 elderly men (age: 70 +/- 1 years; BMI: 26 +/- 1 kg/m(2)), and 10 elderly women (age: 69 +/- 2 years; BMI: 23 +/- 1 kg/m(2)). Results. Postabsorptive leucine flux rates adjusted for fat-free mass (FFM) were not different between elderly and young participants. During the clamp, leucine flux and protein synthesis rates increased less in the elderly participants, and protein breakdown decreased equally. Thus, the net anabolic (protein balance) response to hyperinsulinemia was lower in elderly versus young participants (p=.007) and was highly correlated with the clamp glucose rate of disposal (r=0.671, p <.001), indicating insulin resistance of protein concurrent with that of glucose. From regression analysis, FFM explained 73% of the variance in the anabolic response. Age explained an additional 3%, but was accounted for by markers of adiposity. FFM and percent body fat collectively explained 79% of the variance. Conclusion. Both reduction in absolute FFM and increased adiposity, intrinsic to the aging process. are associated with an altered anabolic action of insulin in stimulating protein synthesis. This alteration may contribute to the progressive muscle loss with aging.