The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and ␤-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50 -76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50 -76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the crosssectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the ␤-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the ␤-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.Klotho; aerobic exercise; arterial stiffness AN INCREASE IN ARTERIAL STIFFNESS is an independent risk factor for cardiovascular morbidity and mortality (22, 51). Arterial stiffness is known to increase with aging (39). Moreover, menopause augments the age-related increase in arterial stiffness (56), and older women have higher arterial stiffness than do men (52). Furthermore, habitual aerobic exercise decreases arterial stiffness in middle-aged and elderly individuals and postmenopausal women (45,47). Several reports have suggested that the mechanisms by which aerobic exercise training decreases the arterial stiffness could be partly mediated by the enhancement of endothelial function, suppression of oxidative stress, and inflammation (24,27,46). However, the precise mechanism underlying the aerobic exercise-induced modulation of arterial stiffness remains unclear.

Using an automated method for detecting mammographic mass, the authors evaluated the relation between quantitatively measured density and the risk of breast cancer in a case -control study among Japanese women. The case subjects were 146 women newly diagnosed and histologically confirmed with breast cancer at a general hospital. A total of 659 control women were selected from those who attended a breast cancer mass screening at this hospital. Significantly increased odds ratios (ORs) of breast cancer were observed for breast densities of 25 -49 and 50 -74%, but not for densities of 75 -100% as compared with 0% in premenopausal women after controlling for covariates (ORs ¼ 4.0, 4.3, and 1.4, respectively). In postmenopausal women, ORs were significantly increased for breast densities of 25 -50% (OR ¼ 3.0) and 50 -100% (OR ¼ 4.2). Total breast area was significantly associated with the risk of breast cancer independent of density percent or dense area in postmenopausal women. These data suggested that mammographic density was associated with the risk of breast cancer in Japanese women as is the case in Caucasian women. However, the associations of the risk of breast cancer with breast size and a high breast density greater than 75%, needs to be confirmed in future studies.

Alzheimer’s disease is a neurodegenerative disorder that affects the central nervous system. In this study, we characterized and examined the early metabolic changes in the triple transgenic mouse AD model (3xtg-AD), and their relationship with the hypothalamus, a key regulator of metabolism in the central nervous system. We observed that the 3xtg-AD model exhibited significantly higher oxygen consumption as well as food intake before reported amyloid plaque formation, indicating that metabolic abnormalities occurred at early onset in the 3xtg-AD model compared with their counterparts. Analysis of gene expression in the hypothalamus indicated increased mRNA expression of inflammation- and apoptosis-related genes, as well as decreased gene expression of Agouti-related protein (AgRP) and Melanocortin 4 receptor (MC4R) at 12 weeks of age. Immunofluorescence analysis revealed that pro-opiomelanocortin (POMC) and NPY-expressing neurons decreased at 24 weeks in the 3xtg-AD model. Four weeks of voluntary exercise were sufficient to reverse the gene expression of inflammation and apoptotic markers in the hypothalamus, six weeks of exercise improved glucose metabolism, moreover, 8 weeks of voluntary exercise training attenuated apoptosis and augmented POMC and NPY-expressing neuronal populations in the hypothalamus compared to the control group. Our results indicated that early onset of metabolic abnormalities may contribute to the pathology of AD, which is associated with increased inflammation as well as decreased neuronal population and key neuropeptides in the hypothalamus. Furthermore, early intervention by voluntary exercise normalized hypothalamic inflammation and neurodegeneration as well as glucose metabolism in the 3xtg-AD model. The data, taken as a whole, suggests a hypothalamic-mediated mechanism where exercise prevents the progression of dementia and of Alzheimer’s disease.

Background: A high percentage of mammographic dense area has been strongly associated with a risk of beast cancer. The present cross-sectional study evaluated the relations of percent density with dietary factors, such as fats, protein, dietary fiber, and soy isoflavones. Methods: Study subjects were 601 (348 premenopausal and 253 postmenopausal) Japanese women who were recruited from a mammographic screening center. The size of the total breast area and the dense area were measured quantitatively using an automated mammographic mass detection method. Intakes of nutrients were estimated with a validated semiquantitative food-frequency questionnaire. Results: The crude means of the percent density were 39.2% and 18.9% in premenopausal and postmenopausal women, respectively. There were no significant associations of any dietary factors with the percent density in premen-