Age-dependent changes in the rate of myofibrillar protein degradation in humans as assessed by 3-methylhistidine and creatinine excretion.

1. Urinary excretion of 3-methylhistidine and creatinine have been measured in normal male and female humans ranging in age from pre-term neonates to 68 years to assess changes in the rate of muscle protein degradation and in muscle mass. 2. The 3-methylhistidine excretion by six adult men was measured before and after subjects were transferred to meat-free diets. It was established that a meat-free diet should be eaten for a minimum of 3 days before urine collection to eliminate exogenous sources of 3-methylhistidine. 3. The 3-methylhistidine/creatinine excretion ratio declined about twofold between normal full-term birth and maturity. The ratio in pre-term neonates was higher than for full-term neonates. 4. The variability of 3-methylhistidine/creatinine ratios between individual untime urine samples within a subject is similar to the variability between different subjects with total daily collections. 5. The 3-methylhistidine content of human muscle averaged 3.63 +/- 0.06 micromol/g for subjects aged between 4 and 65 years with protein accounting for 20.4 +/- 0.8% of muscle weight. These values are used to relate 3-methylhistidine excretion to muscle protein degradation. 6. It is concluded that control groups must be matched by age and sex to the group being examined. Where creatinine excretion is not perturbed it can be used as a reference base for comparisons of 3-methylhistidine excretion to indicate the average fractional degradation rates of muscle protein.