The Effect of Protein and Caloric Restriction and Age on the Rate of Liver Protein Synthesis of Male Rats

The liver protein synthesis rate and protein content were studied in male Wistar rats fed low-, medium-, and high-protein diets at 2 calorie levels for 1 (12 animals per dietary group) or 2 (36 animals per dietary group) years. Ad libitum-fed (A) groups were offered semisynthetic diets containing 12, 20, or 28% casein. Restricted-fed (R) rats fed diets containing 18, 30, or 42% casein were provided two-thirds of the mean quantity of diet consumed by A groups and thus consumed the same amount of protein but one-third fewer calories than their ad libitum-fed controls. The fractional rate of liver protein synthesis was determined by the method of continuous dietary infusion of [¹⁴C]tyrosine. The rate of rise in the specific activity of free tyrosine (rate constant) was approximated for each rat using the rate of rise of ¹⁴C radioactivity in the expired CO₂. The rate constant and the specific radioactivity of the free and protein-bound liver tyrosine were utilized to calculate the fractional rate of protein synthesis.

Restricted-fed rats had growth curves similar in shape but at a lower level than those for ad libitum-fed rats. Mean daily feed intake of A groups showed little variation after 2 months of age (R groups were fed two-thirds of the amount consumed by their ad libitum-fed controls).

Percent survival was increased (p < 0. 003) by caloric restriction. Although caloric restriction resulted in a greater effect on lifespan, an effect of dietary protein intake was also demonstrated. Low dietary protein intake was associated with a low percent survival in both caloric groups

With age, there was a reduction (p < 0.05) in liver protein content. Protein restriction produced a linear decrease (p < 0.03) in liver protein content in 1-year animals only. Caloric restriction was associated with a dramatic increase (p < 0.0001) in liver protein content in both young (1-year) and old (2-year) animals.

The liver protein synthetic rate increased (14%) with age (p = 0.02). In old animals, dietary protein restriction produced a linear increase (p < 0.01) in the rate of liver protein synthesis of both ad libitum- and restricted-fed groups. Young restricted- groups exhibited a similar tendency. A dramatic reduction (p < 0.0001) in the liver protein synthetic rate as a result of caloric restriction was observed in 2-year animals and the same trend was noted in young restricted-fed groups. Rates of protein synthesis exhibited an interaction (p < 0.02) between protein intake and caloric level, that is, R groups showed a linear increase in liver protein synthesis with protein restriction while A groups showed little change.

Caloric restriction delayed the age-associated increase in liver protein synthesis and increased percent survival, while protein restriction was associated with an increase in the liver protein synthetic rate and a reduction in percent survival. These findings support the hypothesis that the mechanism by which caloric restriction increases longevity is through decreased use of the genetic code for protein synthesis that reduces genetic imperfections that may occur during aging.