ビタミンCの不足が老化に及ぼす影響

抄録

Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases androgen-independently with aging. To examine the physiological function of SMP30, we established SMP30 knockout mice and found that they were viable and fertile although lower in body weight and shorter in life span than the wild type when fed autoclaved mouse chow. The mean survival time of these SMP30 knockout mice was approximately 6 months. On the other hand, wild type mice was approximately 24 months. Although phenotypical analysis during the survival interval of SMP30 knockout mice uncovered no obvious abnormalities, immediate postmortem examination revealed atrophy in almost all their abdominal organs. Recently, we identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of animal species. GNL was a key enzyme which involve in vitamin C biosynthesis, and the essential role of SMP30 in this synthetic process was verified by a nutritional study. These knockout mice fed a vitamin C-deficient diet did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary, then died by 136 days after the start of receiving the deficient diet. Thus SMP30 knockout mice developed symptoms of scurvy when fed a vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C biosynthesis. As mentioned above, these mice were shorter in life span than the wild type when fed autoclaved mouse chow contained 〜55mg/kg of vitamin C, which we now know contains too little vitamin C to maintain normal levels of vitamin C in tissues. However, never before did we observe scurvy symptoms in the knockout mice when fed autoclaved mouse chow. Collectively, these results demonstrate that vitamin C deficiency accelerates aging.