Yoshitaka Kondo, Ph.D. Researcher (Molecular Regulation of Aging)
Akihito Ishigami, Ph.D. Team Leader (Molecular Regulation of Aging)
Vitamin C (ascorbic acid) is a water-soluble electron donor that can act as a cofactor in metal ion-dependent enzyme reactions. For example, vitamin C is essential for the synthesis of collagen that is abundant in bone, cartilage, and blood vessels. Primates, including humans, cannot synthesize vitamin C because they have lost the vitamin C-synthesizing enzyme. However, many vertebrates, including mice, retained the ability to synthesize vitamin C. To reveal the physiological role of vitamin C, we developed a mouse that does not produce the vitamin C-synthesizing enzyme. Vitamin C-depleted mice showed symptoms of human scurvy, including decreased collagen content in skin, decreased appetite, femoral fractures, bleeding from blood vessels between the costa and costal cartilage, and eventual death. Thus, these mice are useful models for studying the role of vitamin C in the body.
In human cells, reactive oxygen species (ROS) are generated from oxygen as byproducts of energy production. ROS is thought to worsen age-associated diseases such as diabetes mellitus, non-alcoholic fatty liver disease, atherosclerosis, and cataracts. Vitamin C is a potent ROS scavenger as evidenced by the increased ROS levels in the tissues of vitamin C-depleted mice.
To clarify the relationship between aging and vitamin C, we analyzed our vitamin C-depleted mice. The mean lifespan of the vitamin C-insufficient mice was 6 months, as compared to the 24 month average lifespan of vitamin C-sufficient mice. At the time of death, the vitamin C-insufficient mice showed no tumors or inflammation, but did exhibit aging-related symptoms similar to those seen in humans, including emaciation and tissue atrophy. Furthermore, vitamin C-insufficient mice are prone to age-related hearing loss, cataracts, diabetes mellitus, and chronic obstructive pulmonary disease (COPD). These findings suggest that vitamin C insufficiency accelerates the aging process.
In Japan, the recommended amount of vitamin C is 100 mg per day. The results for vitamin C-insufficient mouse survival suggest that maintaining an adequate intake of vitamin C may mitigate age-related diseases and extend the lifespan of humans.
1. Kondo Y, Inai Y, Sato Y, Handa S, Kubo S, Shimokado K, Goto S, Nishikimi M, Maruyama N, Ishigami A: Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy. Proc Nat Acad Sci USA 103, 5723-5728 (2006)
2. Kondo Y, Sakuma R, Ichisawa M, Ishihara K, Kubo M, Handa S, Mugita H, Maruyama N, Koga H, Ishigami A: Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues. J Agric Food Chem 62 (38), 9286-9295 (2014)
3. Ishigami A, Kondo Y, Nanba R, Ohsawa T, Handa S, Kubo S, Akita M, Maruyama N: SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span. Biochem Biophys Res Commun 315, 575-580 (2004)