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  • br Experimental Procedures br Acknowledgments We

    2023-02-01


    Experimental Procedures
    Acknowledgments We thank the members of the Qing laboratory for helpful suggestions and Biotree Biotech Co., Ltd. (Shanghai, China) for metabolomics analysis and data interpretation. This study was supported by the National Key Research and Development Program of China (Grant 2016YFC1302300 to G.Q.), the National Science Fund for Distinguished Young Scholars (Grant 81725013 to G.Q.), the National Natural Science Foundation of China (Grant 81572736 to G.Q. and 81470332 to H.L.), and the National Science Foundation of China (Grant 31521091 to G.Q.).
    Introduction In Japan, aging can bring with it major problems in both middle and old age. In middle-aged women, various changes occur, including a reduction in fertility and the start of the menopausal syndrome. In old age, it is well known that the average life span is much longer than the number of healthy life years. “Healthy life years” refers to the number of years that people can live actively without severe health problems (e.g. without becoming bedridden or suffering from dementia). According to the Japanese Ministry of Health, in 2013 the difference between the average number of healthy life years and the average life span of women was 12.40 (86.61–74.21) years. This difference in women was greater than the difference found for men, for whom it was 9.02 (80.21–71.19) years. Recent evidence suggests that aging in certain regions of the TMC125 australia occurs earlier in females than in males (Yuan et al., 2012). Moreover, sympathetic neural mechanisms, which influence blood pressure, dramatically changed with aging in females (Narkiewicz et al., 2005). Alzheimer’s disease pathology is more likely to be shown as dementia in women than in men because it may relate to the lack of sex hormones after menopause (Barnes et al., 2005). One of the negative factors that affects aging problems is stress. Stress can affect the aging of the brain and other organs of the body and can exacerbate processes involving the generation of excess free radicals (McEwen, 2002). Six hours of immobilization stress caused oxidative stress in mice (Kumar et al., 2014). Oxidative stress induced by reactive oxygen species (ROS) is the major factor of the aging process (Serrano and Klann, 2004). In addition, social advancement has caused later childbearing in women. The pool of follicles diminishes remarkably with aging, along with the quality of the follicles (Faddy et al., 1992, Tatone et al., 2008). These changes also relate to ROS, which can damage mitochondrial DNA (mtDNA) and contribute to mtDNA mutations (Keefe et al., 1995, Tarin, 1996). As a result, fecundity gradually decreases with aging. In the menopause, disruption of the hormone balance commonly occurs and causes changes in physical condition. Moreover, in middle-aged women there are increased possibilities of being subjected to stress through social responsibilities and domestic problems. Therefore, it is important to improve the quality of life (QOL) in middle age before further aging takes place. It is suggested that one of methods for improving people’s QOL is to improve their nutritional condition. In general, the body weight of elderly people decreases, leading to the loss of lean muscle tissue, which results in sarcopenia, and which is caused by protein-energy malnutrition (Soenen and Chapman, 2013). Concerning this phenomenon, the importance of taking protein in middle-aged and elderly women is emphasized. Recently, the amount of protein consumption in elderly people was given much attention, but still no consideration was given to the specific amino acid balance. This was probably due to a lack of information on amino acid metabolism in middle-aged and elderly people. It is known that some amino acids reduce stress and that some affect sleep. Glycine and ornithine, for example, have been shown to be effective in promoting sleep (Inagawa et al., 2006, Omori et al., 2012). However, it is not known whether amino acid metabolisms could be influenced by aging. Amino acids in the brain have roles in the regulation of mood-related behavior. In the reproductive organs, amino acids are related to protein metabolism that is important for the maintenance of their functions. Accordingly, the aim of the present study was to clarify the influence of aging and stress on both d- and l-amino acid metabolisms in the brain and reproductive organs of middle-aged female mice, as well as on their emotional behavior. This study used middle-aged mice because it is important to clarify the metabolic changes that occur in middle age as an early stage of aging to enable nourishment to be improved in the future.