Toward the realization of a better aged society: messages from gerontology and geriatrics.

1. BACKGROUND: Recent medical advancements, and improvements in hygiene and food supply have led to Japan having the longest life expectancy in the world. Over the past 50 years, the percentage of the elderly population has increased fourfold from 5.7% in 1960 to 23.1% in 2010. This change has occurred at the fastest rate in the world. Compared with France, where the percentage of the elderly population has increased just twofold in the past 100 years, Japanese society is aging at an unprecedented rate. In addition, the percentage of the very elderly (aged 75 years and over), comprising more frail people, exceeded 10% of the nation's population in 2008. In such a situation, many elderly Japanese wish to spend their later years healthy, and wish to achieve great accomplishments in their lives. To achieve that, rather than considering an aging population as a negative social phenomenon, we should create a society where elderly people can enjoy a healthy, prosperous life through social participation and contribution. Factors that hamper the elderly from leading a healthy life include various psychological and social problems occurring in older age, as well as a high incidence of diseases. Therefore, gerontology, which focuses on health promotion of the elderly by encompassing the study of social welfare, psychology, environment and social systems; and geriatrics, which focuses on health care of elderly people and carried out research, education and practices to promote health in the elderly, are becoming more important. Furthermore, along with a need for multidisciplinary care to support geriatric medicine, the development of a comprehensive education system for aged-care professionals is awaited. Thus, we should now recognize the importance of gerontology and geriatrics, and a reform of medical-care services should be made in order to cope with the coming aged society. Population aging is a global phenomenon. The actions being taken by Japan, the world's most aged society, have been closely watched by the rest of the world. Japan's aged society has been posing not only medical, nursing and welfare problems, but also complex problems closely associated with economy, industry and culture. Therefore, to solve these problems, a macroscopic integration and cooperation among industries, education institutions, administration and community through an interdisciplinary approach including medical science, nursing science, nursing care, study of social welfare, social science, engineering, psychology, economics, religion and ethics should be made. Regarding the promotion of gerontology, the "Committee for Establishing a Scientific Community for Sustainable Aged Society" of the Science Council of Japan also prepared a proposal and this was announced on 20 April 2011. 2. CURRENT SITUATION AND PROBLEMS: (1) Promotion of social participation and contribution of elderly people In Japan, the overall labor force rate is expected to decrease in the near future as a result of the low birth rate and high life expectancy. In contrast, many elderly people, particularly the young-old, have sufficient physical strength to fulfil their job duties and make a social contribution. For these people, a social structure where elderly people can work should be developed through re-educating the elderly and providing various job types. Promotion of social participation and contribution of the elderly is expected to cause a substantial increase in the labor force. Furthermore, it is also expected to contribute to not only the upturn of national economic activity through an increase in total consumption, but also a decrease in the number of elderly people who are likely to be in need of care. Therefore, in order for elderly people to be engaged in various social activities, strategies for developing a social structure for re-education, various employment statuses and employment opportunities should be prepared. However, as the total number of jobs is fixed, consideration should also be given to young workers. (2) Fostering medical specialists for aging Older people often suffer from many diseases, together with geriatric syndromes with multiple etiologies. Signs and symptoms vary according to each individual, and are often atypical; therefore, the patients visit different hospitals and receive many screening tests and prescriptions at the same time. To solve this problem, an effective screening system carried out by a primary-care doctor, and privacy-preserving medical data sharing among hospitals and clinics are needed. In a geriatric clinical setting, health-care professionals should be aware of the physical traits of older people who often develop not only dementia, but also geriatric syndromes, such as depression, falls and urinary incontinence, so that a holistic approach with consideration of nursing care is required. However, the existing Japanese medical education system is not prepared for medical professionals enabled to respond to the aforementioned requirements. Thus, the fostering of medical professionals who can provide comprehensive care - especially for the oldest-old - such as geriatric specialists and medical professionals who understand the principles of elderly care, is urgently needed. (3) Diagnosis of elderly-specific diseases and reform of medical-care services In Japan, the diagnostic system for elderly-specific diseases, including dementia, and reform of medical care services are markedly delayed. The current status concerning diagnosis, care and nursing should be investigated to collect academic data. In order to accumulate evidence for providing safe elderly care and nursing, the promotion of clinical research and a marked expansion of geriatric medical centers with high-level medical services are eagerly awaited. (4) Promotion of home-based care and multidisciplinary care To reduce the length of stay in acute hospitals, to reduce the physical burden of health-care professionals working at acute hospitals and to meet the demand of older people who prefer to remain in their own homes, further promotion of home-based care is needed. In addition, "multidisciplinary care" is increasingly needed to meet various demands in the medical care and welfare of the elderly. It is considered important to share countermeasures against the problems of disease prevention, medicine, care and welfare among health-care professionals in medicine, care and welfare, and cooperate by making the best use of health-care professionals' specialties. 3. CONTENTS OF THE PROPOSAL: The subcommittee for aging, thus, provided the following proposal: 1 Development and promotion of systems that enable elderly people to participate socially and make a contribution using an interdisciplinary approach among the various areas, including nursing science, nursing care, study of social welfare, social science, psychology, economics, religion and ethics, as well as medical sciences; 2 Promotion of gerontology, reform and enhancement of geriatrics in undergraduate, postgraduate and lifelong education; 3 Building geriatric medical centers in each area, and accumulating large-scale evidence of geriatric diseases and geriatrics; and 4 Structural development and promotion of home-based care and multidisciplinary care. Through implementation of the above measures, Japan is expected to function as a successful example for the rest of the world.

Raised homocysteine and low folate and vitamin B-12 concentrations predict cognitive decline in community-dwelling older Japanese adults.

BACKGROUND & AIMS: Recently, poor cognition and dementia have been associated with elevated homocysteine and low B vitamin concentrations. The aim of this study is to examine the association in community-dwelling older Japanese adults. METHODS: Ninety-nine subjects (71 women and 28 men; mean age 75 years) were eligible for analysis after exclusion of subjects with high serum creatinine concentrations (1.3mg/dl and over) and those taking vitamin supplements. Fasting blood samples were analyzed for plasma total homocysteine, serum folate, and serum vitamin B-12. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE). RESULTS: Multiple regression analysis revealed that homocysteine concentrations were predicted by concentrations of vitamin B-12 (p<0.001), folate (p<0.005), and creatinine (p<0.001) and age (p<0.005). Scores on the MMSE were associated with concentrations of homocysteine, vitamin B-12, and folate. The association between folate or vitamin B-12 concentrations and MMSE scores remained significant after adjusting for homocysteine concentrations. Folate concentrations, but neither homocysteine nor vitamin B-12 concentrations, were significantly associated with serum albumin concentrations. CONCLUSIONS: Reduced folate and vitamin B-12 concentrations were independently associated with cognitive decline. The correlation between folate and albumin concentrations may imply that the reduction of folate in the Japanese older population is due to nutritional deficiency.

Modulating role of estradiol on arginase II expression in hyperlipidemic rabbits as an atheroprotective mechanism.

We evaluated the effects of a 0.5% cholesterol-enriched diet (HCD) on nitric-oxide synthase (NOS) and arginase expression and the modulating role of 17beta-estradiol (E(2)) on this phenomenon. Thirty oopherectomized rabbits were divided into three groups and treated for 15 weeks. Group I received normal chow; group II, HCD; and group III, HCD plus E(2) pellets. Animals in group II showed an increase in plasma lipids, and they demonstrated atheromatous lesions as well as expression of arginase I and II accompanied by a significant number of BrdU-positive cells in endothelial cells and intimal muscle cells, suggestive of an increase in cellular proliferation. There was significant expression of inducible NOS and increased staining of nitrotyrosine-positive areas. These were not observed in group I animals. In both groups, E(2) levels were low. In group III animals, E(2) supplementation led to a decrease in atheromatous lesions and BrdU-positive cells and reduced expression of both inducible NOS and arginase I and II accompanied by a decrease in nitrotyrosine staining. E(2) levels were increased. Our results suggest that E(2) was responsible for these effects, despite the animals being hyperlipidemic, similar to those in group II. Because arginase is responsible for cell proliferation by converting l-arginine to polyamines, our results indicate that expression of arginase may play an important role in cellular proliferation in atherosclerosis, and inhibition of arginase expression by E(2) may be another potential mechanism in attenuating atherogenesis.

l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits.

The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma NO(2)(-)+NO(3)(-) and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.

Effects of home massage rehabilitation therapy for the bed-ridden elderly: a pilot trial with a three-month follow-up.

OBJECTIVES: To assess the effects of home massage rehabilitation therapy on the bed-ridden elderly. DESIGN: Alternatively allocated trial. SETTING: Subjects' homes, three home nursing stations, 13 visit care stations and one day service centre in Aichi prefecture, Japan. SUBJECTS: Bed-ridden patients who were 65 years and above, no dementia, stable general condition, and receiving no rehabilitation therapy. INTERVENTION: Thirty-minute sessions of home massage rehabilitation therapy by a massage practitioner 2 or 3 days a week for three consecutive months or usual care. MAIN MEASUREMENTS: Barthel Index (BI), Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score. RESULTS: Fifty-three subjects were recruited, 26 in the home massage rehabilitation group (HMG) and 27 in the routine care group without massage (RCG). The protocol was completed for 40 subjects, 22 in the HMG and 18 in the RCG. There were no significant differences between the baseline characteristics of both groups; age, presence of spouse, diseases associated with disabilities and use of day care rehabilitation (p = 0.76, 0.36, 0.94 and 0.71, respectively). The total BI score of the HMG (15.27+/-4.51) at baseline was nonsignificantly lower (p= 0.03) than those of the RCG (11.44+/-5.90). Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score of both groups at baseline were matched (p = 0.12, 0.32 and 0.89, respectively). There were no statistical differences between the intergroup changes over time in BI, Subjective Satisfaction and Refreshment Scale, Apathy Scale and Self-rating Depression Score (p = 0.35, 0.08, 0.70 and 0.55, respectively). CONCLUSION: Home massage rehabilitation therapy did not show a positive effect on the bed-ridden elderly, either mentally or physically. We would require large-size trials to determine whether it is effective.

Green tea catechins inhibit neointimal hyperplasia in a rat carotid arterial injury model by TIMP-2 overexpression.

OBJECTIVE: Although it has been demonstrated that the antioxidant properties of tea catechins reduce atherosclerotic lesions in various animal models of hyperlipidemia, it is not yet clear whether these catechins prevent hyperlipidemia-independent arterial remodeling induced by balloon angioplasty. We evaluated the influence of the administration of the tea extract on vascular remodeling in a rat carotid artery balloon-injury model. METHODS AND RESULTS: Male Wistar rats were supplied drinking water with or without green tea extract (1 mg/ml) supplement. Administration of the tea extract reduced the area of the intima (30%) and the ratio of the intimal area to the medial area (36.2%) in injured arteries compared with those of control rats at 14 days after the injury. Real-time RT-PCR, Western blot, and gelatin zymography revealed a significant increase in tissue inhibitor of matrix metalloproteinase (MMP)-2 (TIMP-2) expression as well as a significant reduction of gelatinolytic net activity and activated MMP-2 levels in the injured arteries as a result of the administration of the tea extract compared with those of control group. Similarly, epigallocatechin-3-gallate, a major constituent of green tea catechins, significantly upregulated TIMP-2 expression in cultured smooth muscle cells. Immunohistochemical analysis showed that the increase of TIMP-2 protein occurred preferentially in the developing neointima. CONCLUSION: These results indicate that catechins inhibit intimal hyperplasia in a rat balloon-injury model through the upregulation of TIMP-2 expression to modulate MMP activity.

Gene transfer of endothelial NO synthase, but not eNOS plus inducible NOS, regressed atherosclerosis in rabbits.

The effects of in vivo gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) genes on severe atherosclerosis were investigated in rabbits. The recombinant adenoviruses, Ad.eNOS and Ad.iNOS, which respectively express eNOS and iNOS, were constructed. Atherosclerosis was induced by a balloon injury followed by a high cholesterol diet for 12 weeks. The rabbits were divided into six groups: Gp cont (no treatment); Gp null (adenovirus sham-infected); Gp eNOS (Ad.eNOS); Gp iNOS (Ad.iNOS); Gp e+i (Ad.eNOS plus Ad.iNOS); and Gp heNOS (a high dose of Ad.eNOS). Examinations were carried out 7 days after gene transfer. Plasma lipid levels were not significantly changed, but transfection with Ad.eNOS (Gp eNOS and Gp heNOS) decreased the tissue cholesterol concentration and regressed atherosclerotic lesions. Vessels treated with Ad.iNOS (Gp iNOS and Gp e+i) showed iNOS staining in the atheroma, and slight staining at other parts of the vessels; those treated with Ad.eNOS showed eNOS staining in the endothelium and subintima, and slight staining at other parts. Ad.eNOS transfection, but not Ad.iNOS or Ad.eNOS+Ad.iNOS transfection, improved the impaired aortic endothelium-dependent relaxation (EDR) and basal NO-dependent response, increased tissue cyclic GMP (cGMP), and decreased the release of O2- from vessels. eNOS treatment showed a decreasing tendency in regions with peroxynitrite staining, MMP1 staining, and suspected apoptosis. In conclusion, in vivo gene transfer of eNOS, but not iNOS or eNOS plus iNOS, regressed atherosclerosis. The relations among NO, O2-, and peroxynitrite may be critical, and lipid resorption from the lesions may be responsible for the regression.

Green tea catechins inhibit the cultured smooth muscle cell invasion through the basement barrier.

Epidemiological studies suggest that green tea consumption is associated with a reduced risk of cardiovascular disease. Antioxidative properties of green tea flavonoids, catechins, have been believed to be involved in the antiatherogenic effect of green tea, since catechins inhibit low density lipoprotein oxidation. The migration of vascular smooth muscle cells (SMCs) from the tunica media to the subendothelial region is a key event in the development and progression of atherosclerosis and post-angioplasty vascular remodeling. Matrix metalloproteinases (MMPs) play a key role in these processes of SMC migration. In the present study, we investigated the effect of catechins on the gelatinolytic activity of MMP-2 that was derived from cultured bovine aortic SMCs. We also investigated the effect of catechins on the SMC invasion through the reconstituted basement membrane barrier. A major constituent of green tea catechins, (-)-epigallocatechin gallate (EGCG), inhibited the gelatinolytic activity of MMP-2 and concanavalin A (ConA)-induced pro-MMP-2 activation without the influence of membrane-type MMP expression in SMCs. EGCG also inhibited the SMC invasion through the basement membrane barrier in a concentration-dependent manner without any influence of SMC migration across the basement membrane protein thin-coated filter. The antagonistic effects of other catechins, namely (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG), on gelatinolytic activity of MMP-2, ConA-induced pro-MMP-2 activation, or PDGF-BB-directed SMC invasion were much less pronounced than those of EGCG. Also, (+)-catechin and (-)-epicatechin failed to show any effect. These findings may suggest that the anti-invasive and anti-metalloproteinase activities involve at least part of the anti-atherogenic action of catechin in accordance with the antioxidant properties of catechin.

Usefulness of soluble dietary fiber for the treatment of diarrhea during enteral nutrition in elderly patients.

OBJECTIVES: We investigated the clinical usefulness of soluble dietary fiber (SDF) for the treatment of diarrhea during enteral nutrition in elderly patients. METHODS: This study included 10 men and 10 women (mean age +/- standard deviation: 79.3 +/- 5.1 y) who had diarrhea during long-term nutrition management. When administering SDF, the initial dose was 7 g and thereafter gradually increased at 1-wk intervals. After 4 wk, the administration was discontinued for 2 wk to confirm the effects of SDF. RESULTS: After the administration of SDF, serum diamine oxidase activity significantly increased (P < 0.001): The water content of the feces decreased significantly after the administration of fiber (P < 0.01). The frequency of daily bowel movements also decreased significantly (P < 0.05). Simultaneously, the fecal features improved. Concerning intestinal flora, there were no significant changes in the total number of bacteria or the number of anaerobic bacteria. The fecal pH decreased significantly 4 wk after the administration of fiber (P < 0.05). The total level of short-chain fatty acids increased significantly 4 wk after the administration of fiber (P < 0.05). There were no significant changes in the various nutritional indices. CONCLUSIONS: The administration of SDF is useful for controlling spontaneous, favorable bowel movement by improving symptoms of small intestinal mucosal atrophy and normalizing the intestinal flora.