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.

Essential role of caspase-8 in p53/p73-dependent apoptosis induced by etoposide in head and neck carcinoma cells.

BACKGROUND: Caspase-8 is a key upstream mediator in death receptor-mediated apoptosis and also participates in mitochondria-mediated apoptosis via cleavage of proapoptotic Bid. However, the role of caspase-8 in p53- and p73-dependent apoptosis induced by genotoxic drugs remains unclear. We recently reported that the reconstitution of procaspase-8 is sufficient for sensitizing cisplatin- but not etoposide-induced apoptosis, in chemoresistant and caspase-8 deficient HOC313 head and neck squamous cell carcinoma (HNSCC) cells. RESULTS: We show that p53/p73-dependent caspase-8 activation is required for sensitizing etoposide-induced apoptosis by utilizing HOC313 cells carrying a temperature-sensitive p53G285K mutant. Restoration of wild-type p53 function under the permissive conditions, together with etoposide treatment, led to substantial transcriptional activation of proapoptotic Noxa and PUMA, but failed to induce apoptosis. In addition to p53 restoration, caspase-8 reconstitution was needed for sensitization to etoposide-induced apoptosis, mitochondria depolarization, and cleavage of the procaspases-3, and -9. In etoposide-sensitive Ca9-22 cells carrying a temperature-insensitive mutant p53, siRNA-based p73 knockdown blocked etoposide-induced apoptosis and procaspase-8 cleavage. However, induction of p73 protein and up-regulation of Noxa and PUMA, although observed in Ca9-22 cells, were hardly detected in etoposide-treated HOC313 cells under non-permissive conditions, suggesting a contribution of p73 reduction to etoposide resistance in HOC313 cells. Finally, the caspase-9 inhibitor Ac-LEHD-CHO or caspase-9 siRNA blocked etoposide-induced caspase-8 activation, Bid cleavage, and apoptosis in both cell lines, indicating that p53/p73-dependent caspase-8 activation lies downstream of mitochondria. CONCLUSIONS: we conclude that p53 and p73 can act as upstream regulators of caspase-8, and that caspase-8 is an essential mediator of the p53/p73-dependent apoptosis induced by etoposide in HNSCC cells. Our data suggest the importance of caspase-8-mediated positive feedback amplification in the p53/p73-dependent apoptosis induced by etoposide in HNSCC cells.

Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice.

OBJECTIVE: Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. METHODS: C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. RESULTS: The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. CONCLUSION: Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus.

Orexin-A does not stimulate food intake in old rats.

Aging is associated with a progressive decrease in appetite and food intake. Both A and B orexins, expressed in specific neurons of the lateral hypothalamic area, have been implicated in the regulation of sleep and feeding. In this study, the stimulatory effect of intracerebroventricular administration of the orexins on food intake was compared between young (4-mo-old) and old (25- to 27-mo-old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses (0-30 nmol) of orexins were injected into the left lateral ventricle without anesthesia. Food and water consumptions were measured at 1, 2, and 4 h after injection. The protein levels of orexin receptors, a specific receptor for orexin-A (OX1R) and a receptor for both orexin-A and -B (OX2R), in the hypothalamus were determined by Western blot analysis and compared between young and old rats. Intracerebroventricular administration of orexin-A stimulated food intake in a dose-dependent manner in young rats. However, no effects were observed at any dose in old rats. The protein level of OX1R in the hypothalamus was significantly lower in old rats than in young rats, although the protein level of OX2R was comparable between groups. Results of the present study indicate that the function of the orexin system is diminished in old rats. The decrease in the OX1R protein level in the hypothalamus could be responsible for orexin-A's lack of stimulation of food intake in old rats.