Almost all elderly people show brain atrophy and cognitive dysfunction, even if they are saved from illness, such as cardiac disease, malignancy and diabetes. Prevention or delay of brain senescence would therefore enhance the quality of life for older persons. Because oxidative stress has been implicated in brain senescence, we investigated the effects of green tea catechin (GT-catechin), a potential antioxidant, in senescence-accelerated (SAMP10) mice. The mouse is a model of brain senescence with short life span, cerebral atrophy and cognitive dysfunction. Mice were fed water containing 0.02% GT-catechin from 1- to 15-month-old. The mean dose was about 35 mg/kg/day. We found that daily consumption of GT-catechin prevented memory regression and DNA oxidative damage in these mice. GT-catechin did not prolong the lifetime of SAMP10 mice, but it did delay brain senescence. These findings suggest that continued intake of GT-catechin might promote healthy ageing of the brain in older persons.

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To evaluate the psychosocial effect on lifespan and cognitive function, this study investigated the effect of confrontational housing on mice because conflict among male mice is a psychosocial stress. In addition, it investigated the anti-stress effect of theanine (γ-glutamylethylamide), an amino acid in tea. Mice were housed under confrontation. That is, two male mice were separately housed in the same cage with a partition for establishing the territorial imperative in each mouse. Then, the partition was removed and mice were co-housed confrontationally (confront-housing) using a model mouse of accelerated-senescence (SAMP10) that exhibited cerebral atrophy and cognitive dysfunction with ageing. It was found that mice began to die earlier under confront-housing than group-housed control mice. Additionally, it was found that cerebral atrophy, learning impairment and behavioural depression were higher in mice under the stressed condition of confront-housing than age-matched mice under group-housing. Furthermore, the level of oxidative damage in cerebral DNA was higher in mice housed confrontationally than group-housed control mice. On the other hand, the consumption of purified theanine (20 μg/ml, 5-6 mg/kg) suppressed the shortened lifespan, cerebral atrophy, learning impairment, behavioural depression and oxidative damage in cerebral DNA. These results suggest that psychosocial stress accelerates age-related alterations such as oxidative damage, lifespan, cognitive dysfunction and behavioural depression. The intake of theanine might be a potential candidate for suppression of disadvantage under psychosocial stress.

Colon cancer is one of the major causes of cancer-related deaths worldwide. Oxidative stress, particularly oxidative damage to DNA, is recognized to play a role in the process of carcinogenesis.1) When cellular defense systems are overwhelmed, oxidative stress results in damage to cellular constituents including the formation of DNA adducts, peroxidation of lipids, degradation of proteins and sugars, and so on.2-4) 8-Oxo-7,8-dihydroguanine (8-oxoG) is a major oxidative DNA adduct 5) that has attracted particular attention since it is correlated with mutagenic and/or carcinogenic processes. [6][7][8] The presence of 8-oxoG residues in DNA strands leads to misreading during DNA replication, 6,9) so that the presence of 8-oxoG increases the possibility of mutagenesis. The contents of 8-oxoG or 8-oxo-2Ј-deoxyguanosine (8-oxodG), its nucleoside, have been found to be increased in target organs of animals treated with a variety of oxidative carcinogens, [10][11][12] and thiobarbituric acid reactive substances (TBARS) are widely used as a marker of in vitro lipid peroxidation. 13)Epidemiological and experimental studies suggest the strong influence of diet on colon cancer. A number of studies demonstrate the importance of natural products as chemopreventive agents.14,15) Coumarins comprise a group of natural compounds widely distributed in plants 16) that have recently attracted much attention because of their broad biological activities. Esculetin (6,7-dihydroxycoumarin) is known to be a 5-and 12-lipoxygenase inhibitor and to inhibit the production of leukotrienes and 5-hydroxyeicosatertaenoic acid through the lipoxygenase pathway.17) Esculetin also scavenges hydroxyl radicals 18) and inhibits lipid peroxidation in rat liver. 19) We have previously observed that esculetin and its glycoside, esculin, suppress the formation of 8-oxodG in the DNA of cultured human diploid fibroblasts treated with linoleic acid hydroperoxide and ferric ion, 20) and that esculin is converted to esculetin in the cells. 21) Furthermore, it has been reported that esculetin inhibits mammary carcinogenesis. 22,23) 1,2-Dimethylhydrazine (DMH) is an alkylating carcinogen that causes neoplastic changes in colonic mucosa at a level proportional to the quantity of methylated DNA adducts induced in colonic crypt cells.24) DMH-induced colon tumors are currently the most popular models in which to study the morphology, pathogenesis, prevention, and treatment of colorectal cancer.25) Aberrant crypt foci (ACF), first observed in the colonic mucosa of carcinogen-treated rodents, 26) are considered to be preneoplastic lesions, 27) since they are observed at high frequency in the colonic mucosa of patients with colon cancer 28) and rodents treated with colon carcinogens. 29)ACF can be readily identified topographically in methylene blue-stained whole colons of rodents administered carcinogenic agents, and ACF and their growth are thought to be useful indices of the effects of carcinogens and agents preventing carcinogenesis in the colon. 30) In this study, ...

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