I here reviewed the genetic and environmental factors that determine the lifespan of animals. Caloric restriction extends the lifespan of animals in various species. A monkey experiment with 70% caloric restriction showed delayed onset of age-related diseases such as atherosclerosis, osteoporosis, and cognitive decline. The sirtuin gene family is a major category of longevity genes that regulate the aging processes of cells. Sir-2 is one of the first genes found in yeast, which encodes NAD-dependent histone deacetylase. Professor Guarente at MIT discovered that caloric restriction increases NAD in cells, which then activates the Sir-2 gene that controls aging processes and cellular metabolism. I also reviewed an epidemiological report that showed the preventive effects of a Mediterranean diet on Alzheimer's disease. Another study showed that fruit and vegetable juices play an important role in delaying the onset of Alzheimer's disease, particularly among those who are at high risk for the disease. Altogether, lifestyle improvements with specific dietary habits play an important role in the prevention of age-related diseases such as Alzheimer's disease and osteoporosis.

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While anti-aging medicine is the discipline aimed at achieving health and longevity, gynecological anti-aging is not limited to that. Menopausal disorders are mainly caused by the deficiency of estrogen. Estrogen deficiency produces various disorders including hot flash or sweating and increases the risk of hyperlipidemia, arteriosclerosis, and osteoporosis. To treat them, hormone replacement therapy is provided and its safety is being reaffirmed. In Japan, where there is a growing tendency for delayed marriage and childbirth, pre-pregnancy anti-aging is also important as a countermeasure to the falling birth rate. Ovarian anti-aging to prevent the decline in ovarian function requires a systemic and holistic approach. Anti-aging starting from the fetal period is based on the theory of DOHaD (developmental origin of health and disease). Since nutrition and environment during pregnancy are associated with lifelong disease at later stages, starting anti-aging during pregnancy is an efficient and effective approach to prevent adult diseases.

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Anti-aging medicine, which is defined as life extension science by multidisciplinary scientific fields, is particularly important in aging societies such as Japan. The basic concept of anti-aging medicine includes prevention of aging in tissues/ organs, prevention of diseases and subsequent increase of quality of life. However, not only the prevention, but also the restoration of aged tissues/ organs should be important. Particularly for most of the aging population, the appearance related to aging of the face could be improved. Plastic surgery mainly offers the improvement of appearance by either surgical or non-surgical approaches, which specifically include blepharoplasty for blepharoptosis, rhytidectomy for aging face, intense pulse light, lasers, chemical peeling for pigmented lesions and facial fillers and botulinum toxin for wrinkles. Since all such procedures should be evidence-based, patients and physicians involved in this field should understand the mechanisms, indications and limitations of each treatment.

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A lot of adults come to skin clinics asking for anti-aging treatment of pigment spots, wrinkles, white hair, and diffuse hair loss. Currently, there is confusing information about hair care and hair restoration, so there is a need for correct information on maintaining beautiful hair. Firstly, you should know the reason why you are shedding hair. There are several reasons for hair loss : aging, androgenic alopecia, alopecia areata, and telogen effluvium, among others. Secondly, you should get treatment according to evidence-based medicine. Finally, do not forget that beautiful hair is produced by a healthy body. Nutrition, sleeping, and shampoo are very important for the health of your hair and scalp. Checking factors in your daily life is also useful for healthy and beautiful hair.

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Objective: In the Vienna classification, esophageal non-invasive neoplasms are classified as low-grade dysplasia (LGD), high-grade dysplasia (HGD), CIS and suspicion of invasive carcinoma. Polycomb group proteins EZH2 and Bmi-1 are involved in the transactivation of p16 ^INK4a and p53, and have been implicated in the carcinogenesis, progression, and poor prognosis of several cancers;however, their role in early esophageal carcinogenesis has not yet been elucidated. Therefore, in the current study, we examined the expression of EZH2 and Bmi-1 in association with p53 and p16 ^INK4a during esophageal squamous carcinogenesis. Materials: We used a series of 60 esophageal squamous intraepithelial lesions (58 patients), resected endoscopically or surgically at Juntendo University Hospital between 2007 and 2011. The 58 patients comprised 50 males and 8 females, with a mean age of 67.1 years (range, 51-81 years). According to the Vienna classification, we classified the lesions into LGD (category 3), HGD (category 4.1), and CIS (category 4.2) to identify possible biological differences between these lesions, 14 low-grade dysplasia (LGD), 23 high-grade dysplasia (HGD), and 23 carcinoma in situ (CIS) specimens. Methods: Immunohistochemical analysis was performed on 3-μm sections of formalin-fixed, paraffin-embedded tumor tissues. Monoclonal antibodies used in the present study were against EZH2, Bmi-1, p16 ^INK4a, p53, and Ki-67. Immunohistochemical results of each protein were scored as immunolabeling scores (ILSs) from 0 to 3 points according to each quarter of occupation of the squamous epithelium, and were analyzed on the basis of the clinicopathologic variables. Results: All of these lesions had male predominance. Tumor size in CIS was significantly larger than that in LGD (p<0.05). ILSs for all proteins but p16 ^INK4a showed significant stepwise increases from LGD to HGD to CIS (p < 0.05-0.001). Furthermore, the expressions of all proteins but p16 ^INK4a were positively related to each other. However, 3 lesions of LGD (21%), 8 lesions of HGD (35%), and 6 lesions of CIS (26%) demonstrated p16 ^INK4a expression, even under the co-expression of EZH2 and Bmi-1. In HGD, high-EZH2 ILS was significantly associated with larger tumor size (p < 0.05). In addition, high-p53 ILS was associated with larger tumor in CIS (p<0.05). Conclusions: This study indicates that the overexpression of polycomb group proteins EZH2 and Bmi-1, along with p53 and Ki-67, but not p16 ^INK4a, has an important role during the early stages of esophageal squamous carcinogenesis. Interestingly, unlike other malignant tumors, for example, squamous cell lung cancer, cholangiocarcinoma and colorectal cancer, a minor subset of cases of esophageal squamous intraepithelial neoplasia exhibit the p16 expression, even under the coexpression of EZH2 and Bmi-1.

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Objectives : Vascular calcification causes cardiovascular disease or high mortality in chronic kidney disease (CKD) patients. Although iron (Fe) is an inducer of free radicals, we usually use it to improve anemia in CKD patients. The objective of the present study was to determine whether Fe administration accelerates the development of vascular calcification in adenine-induced uremic rats. Materials : Twenty-four 10-week-old male Sprague-Dawley (SD) rats were used in this study. Methods : The rats were divided into four groups as follows : 1) untreated rats as a control group, 2) rats fed a normal diet with Fe administration intraperitoneally (Fe-control group), 3) rats fed an adenine-enriched diet (uremic group) and 4) rats fed an adenine-enriched diet with Fe administration (Fe-uremic group). Iron dextran or sterile saline was administered once a week for 5 weeks. Blood samples were obtained from these rats at the time of sacrifice. Vascular calcification areas in the thoracic aorta were evaluated by Von Kossa's staining. FGF23 in sera and RUNX2 and PiT-1 expression in the aorta were also examined. Results : Fe administration did not produce significant changes in renal function, or the level of hematocrit, serum phosphate or calcium. However, Fe administration suppressed the development of vascular calcification and the expression of PiT-1 in the uremic group. Conclusions : It appears that Fe administration may reduce vascular calcification by the suppression of PiT-1 expression and prevention of osteoblastictransdifferentiation in vascular smooth muscle cells.

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Purpose : Asa part of the World Health Organization (WHO) World Mental Health Survey Initiative (WMH), epidemiologic studies of mental health problems including mental disorders were carried out in 11 regions in Japan. Of these studies, this paper reports the actual situation of mental health in a metropolitan area of Japan. Subjects and Methods : The subjectsin thiss tudy were 1010 men and women over 20 yearso f age, living in I ward, Y city. Interviews were carried out face-to-face between the interviewer and the subject, and WMH computer-assisted personal interview (CAPI) was used. The study was conducted between November 2005 and June 2006. Results : Valid responses were obtained from 377 individuals (response rate : 40.9%). The lifetime prevalence of mental disorders was approximately 40% for both sexes, and the 12-month prevalence of mental disorders for women was twice that for men. In terms of age, people in their 20s had the highest prevalence. Among specific disorders, major depression disorder was the most prevalent in mood disorders. Suicidal behavior was seen in both men and women. Approximately 4% of the subjects had consulted a psychiatrist for mental health problems. Discussion and Conclusion : The trend of results obtained here was the same as in previous studies. There wasno great difference between the percentages of those who consulted a psychiatrist and those who consulted a non-psychiatrist physician. This showed the importance of the role of non-psychiatrist physicians for medical treatment in a metropolitan area of Japan.

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Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in patients with both type 1 and type 2 diabetes. Almost 30% of type 1 or 2 diabetic patients develop diabetic nephropathy despite strict blood glucose and/or blood pressure control. In human glomeruli, the expansion of diffuse mesangial matrices, exudative lesions and/or segmental nodular sclerosis are pathological characteristics of diabetic nephropathy. The spontaneous mouse model, i. e. the KK-A^y mouse, was produced through the transfer of the yellow obese gene (A^y allele) into the KK mouse. The diabetic phenotype in this mouse is more severe than that in KK mouse. In 2006, Ito et al. reported that the pathological changes in the glomeruli of KK-A^y mice were consistent with those in the early stage of human diabetic nephropathy ¹⁾ . In electron microscopy, a diffuse thickening of the glomerular basement membrane (GBM) was observed in this model mouse. Advanced glycation end products (AGEs) and the transforming growth factor-β (TGF-β) protein appeared to be localized in the glomerular mesangial matrices. The KK-A^y mouse, especially in terms of histopathological findings, is considered to be a suitable animal model for type 2 diabetic nephropathy ²⁾ . The objective of this review is to introduce a new strategy for the treatment of type 2 diabetic nephropathy using the KK-A^y mouse.

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The patient was a 41-year-old man with a past history of left testicular seminomatous germ cell tumor diagnosis and resection. He had right scrotum swelling nine years later. He underwent right high orchiectomy, and was diagnosed with non-seminoma. Bilateral testicular tumor is a rare disease, which usually occurs in children and younger men. The prevalence of bilateral testicular tumors including concurrent or metachronous tumors is 1-4%. In patients with metachronous bilateral testicular tumors, secondary tumor generally occurs within five years. However, there is a possibility of it developing over 10 years later. As such, there is a need for long-term observation. We report a case of metachronous bilateral testicular tumor.

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