Frailty amplifies the effects of aging on protein metabolism: role of protein intake.

BACKGROUND We previously showed that muscle contributes less to whole-body protein breakdown with healthy aging. OBJECTIVE We hypothesized that frailty further compromises protein metabolism and that short-term protein supplementation improves protein status. DESIGN Protein metabolism was studied with the oral, 60-h [(15)N]glycine and N(tau)-methylhistidine methods in 8 frail and 13 healthy elderly women during a 9-d isoenergetic, isonitrogenous formula diet and then after increased protein intakes in the frail women, to match the intakes of healthy subjects, for 12 d. RESULTS Compared with healthy women, frail women had higher rates of whole-body protein synthesis and breakdown per kg fat-free mass and lower rates of muscle protein breakdown when expressed as total amounts per day but higher rates when expressed per kg muscle. Because muscle mass was lower in frail women, the contribution of muscle to whole-body protein breakdown was lower and that of nonmuscle lean tissues was higher. The protein-enriched diet had no effect on these variables but resulted in an increase in net endogenous protein balance and a positive nitrogen balance at the end of the diet period. CONCLUSIONS Frailty exacerbates age-related changes in protein metabolism by inducing an increase in muscle protein catabolism and a decrease in muscle mass. At low protein intakes, the increase in muscle catabolism may be a form of protection for both nonmuscle lean tissue mass and function at the expense of muscle mass. Frail women maintained the capacity to retain nitrogen after increased protein intakes, which could convey health benefits if sustained over a long enough period to result in lean tissue accretion.