Canavanine-induced longevity in mice may require diets with greater than 15.7% protein

In order to determine if this effect also obtains at more moderate dietary protein concentrations, 30 female BALB/c mice were fed a basal diet with 14% protein (15.7% dry matter basis) and another 30 were fed the same diet plus 1% canavanine.Neither mean (Control 873.2 d, Canavanine 870.0 d; SEM = 34.2 d; P = 0.949 from ANOVA) nor median (Control 902 d, Canavanine 884.5 d; P = 0.9058 from Mann-Whitney) lifespans differed between groups.Although mean antinuclear antibody (ANA) titers did not differ between control and canavanine-treated mice at 833 days of age (19.84 vs 20.39 respectively; SEM = 2.64; P = 0.889 from ANOVA), one canavanine-treated mouse displayed an outlying ANA value of 50 (next lower value = 30) denoting possible early sign of incipient autoimmune disease in that individual.There may be an interaction between dietary protein level and canavanine with respect to lifespan in mice.L-canavanine is a common non-protein amino acid found naturally in alfalfa sprouts, broad beans, jack beans, and a number of other legume foods and animal feed ingredients [1] at up to 2.4% of food dry matter. This analog of arginine (Figure 1.) can also block NO synthesis [2-5], interfere with normal ammonia disposal [6,7], charge tRNAarg, cause the synthesis of canavanyl proteins [8], as well as prevent normal reproduction in arthropods [9] and rodents [10].Canavanine has also been reported to induce a condition that mimics systemic lupus erythematosus (SLE) in primates [11,12], to increase antibodies to nuclear components and promote SLE-like lesions in auto immune-susceptible (e.g., (NZB X NZW)F1) mice [13].In our previous study [14], eighteen female BALB/c mice were fed a 23.4% protein diet containing 1.56% L-canavanine sulfate (equivalent to 1% L-canavanine base) and eighteen control mice received control diet (23.4% protein) from 84–477 days of age. More canavanine-fed mice (16 of 18) survived to age 477 days than those fed the basal diet (9 of 18) (X 2 with Yates corr