Rapid improvement of canine cognitive dysfunction with immunotherapy designed for Alzheimer's disease

Immunotherapy against amyloid-β(Aβ) may improve rodent cognitive function by reducing amyloid neuropathology and is being validated in clinical trials with positive preliminary results. However, for a complete understanding of the direct and long-term immunization responses in the aged patient, and also to avoid significant side effects, several key aspects remain to be clarified. Thus, to investigate brain Aβ clearance and Th2 responses in the elderly, and the reverse inflammatory events not found in the immunized rodent, better Alzheimer"s disease (AD) models are required. In the aged familiar canine with a Cognitive Dysfunction Syndrome (CDS) we describe the rapid effectiveness and the full safety profile of a new active vaccine candidate for human AD prevention and treatment. In these aged animals, besidesa weak immune system, the antibody response activated a coordinated central and peripheral Aβ clearance, that rapidly improved their cognitive function in absence of any side effects. Our results also confirm the interest to use familiar dogs to develop innovative and reliable therapies for AD.

Vanhusten hyvä kotona asuminen: tutkimusta kuntatuottavuudesta, älykodeista ja apuvälinepalveluprosesseista

The purpose of the research was to investigate operational processes related to home care of the elderly as well as use of assistive devices in smart home environments, and operational processes that are generally related to use of assistive devices – from the point of view of productivity improvement. The themes were looked into from the points of view of both the elderly and care personnel. In addition, perspectives of near relatives of the elderly, of the larger service system as well as of companies that provided assistive devices to the smart homes were taken into consideration. In the study of home care processes, 32 customer interviews and 17 employee interviews were carried out. This report contains a summary that is based on a separate report of the home care study. The study of home care was conducted in 2006. The use of technological and mechanical assistive devices and the related operational processes were investigated with the help of the smart home pilot in 2007–2008. The study is described in this report. The smart home pilot was implemented in four different housing service units for elderly people at Lahti, Nastola and Hollola. They were in use during short-term housing periods related to, for instance, end of hospitalisation, holidays of caring relatives and assessment of living and housing conditions. More than 60 different assistive devices and technologies were brought to the smart homes. During the pilot period, experiences of customers and personnel as well as processes related to the use of assistive devices were investigated. The research material consisted of 20 survey questionnaires of personnel and customers, four interviews with customers, five interviews with personnel, feedback survey responses from 14 companies, and other data that were collected, for instance, in orientation events. The research results highlighted the need for tailored services based on an elderly person’s needs and wishes, while taking advantage of innovative and technological solutions. As in the earlier home care study, also assistive device-related operational processes were looked into with the help of concepts of ‘resource focus’, ‘lost motion’ and ‘intermediate landing’. The following were identified as central operational processes in assistive device-related services (regardless of the service provider): (1) acquisition process of technologies and assistive devices as well as of rearrangement and rebuilding works in the home, (2) introduction and orientation process (of the elderly, their relatives and care personnel), (3) information and communication process, and (4) service and monitoring process. In addition, the research focused on design and desirability of assistive devices as well as their costs, such as opportunity costs. The process-based points of view gave new knowledge that may be used in the future to develop service processes and clarify their ownership so that separately managed cross-functional processes could be built with participants from different sectors to operate alongside organisations of elderly care. Development of functionality of assistive device-related services is a societally significant issue.

Les infections pneumococciques: état des lieux et perspectives en matière de vaccination de l'adulte [Pneumococcal infections: Appraisal and perspectives in terms of adult vaccination].

Pneumococcal diseases are the first cause of bacterial infections in adult and in the aged adult. While its considerable morbi-mortality is potentially preventable through vaccination, the interest of anti-pneumococcal vaccination in these populations is still debated. Effectiveness appraisal of current anti-pneumococcal vaccines and the perspectives in terms of preventive strategies against Streptococcus pneumoniae infections in the adult population are presented.

Elämänlaatu ja iäkkäiden kaatumisten ehkäisy

Quality of life and fall prevention among the aged Improvement of quality of life is considered to be one of the most important goals of prevention, treatment and rehabilitation among the aged. The study aimed to describe and assess fall prevention interventions as a quality of life indicator, and to describe the social dimension of health-related quality of life among the aged. In addition, it aimed to assess the effects of fall prevention intervention on quality of life among the aged. The study was implemented by using a methodological triangulation. The data in the systematic review was retrieved from the databasis of medical and nursing sciences. Home-dwelling aged (n=19) participated in the qualitative study of a social dimension of quality of life. The data was gathered by the thematic interview method. The quantitative multifactorial fall prevention study comprised 591 participants, either the aged living at home or in sheltered housing, showing an increased risk of falling. Participants were randomized into an intervention or a control group. Follow-up measurements were carried out after a 12 month intervention. The data was collected by the 15D quality of life instrument and a structured questionnaire. Based on the systematic review, only in a few studies fall prevention produced positive effects on dimensions of quality of life (physical function, social function, vitality, mental health, environmental domain). Based on the thematic interview the social dimension of quality of life consisted of three themes: personal values, personal milieu and personal daily life. Based on the fall prevention program, depressive symptoms and distress decreased, managing in usual activities improved, sexual activity and phone contacts increased among men. In women, managing in usual activities improved, socializing increased and discomfort and symptoms decreased. Within the groups, self-perceived health improved among women in the intervention group and among men in the control groups. In addition, fear of falling and feelings of insecurity reduced among women in the intervention group. Personal daily life with its activities opened up new perspectives into the social dimension of good quality of life, which was emphasized especially in the interviews of the oldest participants. Multifactorial fall prevention can affect positively some physical and psychosocial dimensions of quality of life among the community-dwelling aged. Additional studies with larger sample sizes, longer follow-up periods and multiple outcome measures are needed. Fall prevention intervention may affect quality of life by different mechanisms, and the quantitative and qualitative assessment of its effects should also be included in the interventions of randomized controlled trials.

Descripció de la tipologia d'usuaris derivats al servei de Teràpia Ocupacional Domiciliària a la comarca d'Osona: estudi descriptiu preliminar

Introducció Aquest treball, aborda l'atenció domiciliaria a les persones amb dependència des de la perspectiva de la teràpia ocupacional a la comarca d’Osona. Conèixer aquesta tipologia de persones i la seva problemàtica, ha de servir per adaptar les infraestructures d’aquests serveis a fi de donar millor resposta a les seves necessitats. Objectiu Descriure la tipologia d'usuaris que es deriven al servei de Teràpia Ocupacional Domiciliària a la comarca d'Osona Metodologia S'ha realitzat un estudi descriptiu preliminar d'una mostra (n=65) de usuaris de la base de dades del Banc D'ajudes Tècniques (BAT Osona) del Consell Comarcal d'Osona. En aquest estudi s'han analitzat les variables de sexe, edat, nivell funcional, diagnòstic, situació familiar, agents derivadors, motius de derivació i problemàtica principal detectada. Resultats S'indica un perfil femení de la mostra (72,09%), amb una mitjana d'edat de 74,41 anys. A nivell funcional, la mitjana de puntuació ha estat de 65 punts en l'Ìndex de Barthel, en persones amb patologia osteoarticular en el 18,60% dels casos. La situació familiar situa un perfil compartit de persones que viuen en família (41,86%) o soles (39,53%). En les derivacions al servei, el 58,13% dels casos es fa des dels Ajuntaments i per dificultats en el quarto de bany (46,51%). La problemàtica més detectada en aquests domicilis és la dificultat per l'accés a la banyera (67,40%). Conclusió Aquests resultats ens indiquen una clara tipologia de persones que s’han d’atendre i unes problemàtiques en la seva vivenda que provoquen serioses dificultats de desenvolupament funciona. Es precís, en futures investigacions acotar encara més aquets perfils i problemàtiques a fi de precisar les estratègies d’intervenció i optimitzar millor aquest tipus de recursos.

Centre de dia a la ctra. de Sóller, 66, de Palma

Award-winning

Indicadores sociales y psicosociales de calidad de vida de las personas mayores en un municipio = Social and psychosocial quality of life indicators of older persons in a municipality

A research about the quality of life of the older persons of a municipality starting from the analysis of the perceptions, evaluations and expectations related to concrete spheres of their lives (familiar characteristics, housing, health, nearby environment, activities, needs and dependencies and persons helping them to satisfy needs) is presented. Answers to 1988 questionnaires obtained from two representative samples of older per - sons living in private homes in the city have been analysed: persons over 65 years old and a specific one composed by a sub-sample of the general one, with persons over 75 years living alone. Data shaping contextual indicators related to housing have been analysed. The auto - nomy to drive and the evaluation of on’s health seem to be positive indicators to take in account while sutying quality of life at these ages. Sentinel indicators of the physical and relational conditions in the family and indicators of dependency are analysed as well. The evaluations of the older persons about their own life conditions are also analysed through psychosocial indicators connected to housing, nearby environmenent, their activities andincomes. The results obtained are applicable in order to improve the decision making process in social intervention programmes developed in the field of ageing aiming to take into account their perspectives

Accelerated ageing like a vigour test to diasporas of Myracrodruon urundeuva Fr. Allem

This work established the adequate temperature and the period of exposition for the accelerated ageing test with diasporas of Myracrodruon urundeuva from an area of the Cerrado in the state of Mato Grosso, Brazil. Before and after the ageing, at the temperatures of 40ºC, 41ºC, 42ºC and 45ºC combined with periods of 12, 18, 24, 30 and 36 hours, the water content and germination were evaluated. For each treatment, 12g of diasporas in mini chambers with 40 mL of distilled water were submitted to the accelerated ageing test. A total of 100 diasporas, divided into four replications, in plastic boxes, on two sheets of blotting paper, in germinator at 25ºC and 8 hours of photoperiod were germinated. In all treatments the content of water of the aged diasporas was superior to 20% and this value stabilized itself between 25% and 28%, from the 18 hours of exposition. Independently of the tested periods, the ageing at the temperatures of 40ºC, 41ºC and 42ºC did not affect the germination. After the ageing at 45ºC, the germination did not differ among the periods of 12, 18 and 24 hours of exposition, but in all these periods it was inferior to the control and superior to the periods of 30 and 36 hours. In these last two periods, fungi were observed. The accelerated ageing of diasporas of Myracrodruon urundeuva should be conducted at the temperature of 45ºC, during the exposition periods of 12 to 24 hours.

Kaatumisvaaraa lisäävät lääkkeet; Porissa toteutettu iäkkäiden monitekijäinen kaatumisten ehkäisy

Kaatumiset ovat ikääntyvien yleisimpiä tapaturmia. Niiden seuraukset voivat olla vakavia. Yksilöllisesti toteutetut ehkäisyohjelmat ovat vähentäneet kaatumisvaarassa olevien iäkkäiden kaatumisia. Psyykenlääkkeiden on osoitettu lisäävän kaatumisia ja murtumia. Niiden lopettaminen on vähentänyt kaatumisvaaraa. Monitekijäiset ehkäisyohjelmat kuvaavat harvoin psyykenlääkkeiden vähentämisen menetelmiä ja tuloksia. Satunnaistettuun, kontrolloituun kaatumisten moneen vaaratekijään kohdistettuun ehkäisytutkimukseen osallistui 591 porilaista. Tässä tutkimuksessa selvitettiin kotona asuvien 65 vuotta täyttäneiden, tutkimusta edeltäneiden 12 kuukauden aikana ainakin kerran kaatuneiden henkilöiden psyykenlääkkeiden käyttö, niiden vähentämisen onnistuminen ja vaikutus sekä ehkäisyohjelman merkitys kaatumisten ilmaantumiseen. Lisäksi tutkittiin kaatumisvamman takia hoitoon hakeutuneiden kaatumisvaaratekijöiden tunnistamista ja uusien kaatumisten ja murtumien ehkäisemiseksi suunniteltuja toimenpiteitä perusterveydenhuollossa ja erikoissairaanhoidossa. Joka neljäs osallistuja käytti säännöllisesti psyykenlääkkeitä. Kertaneuvonta niiden vähentämisestä, johon sisältyi kirjalliset ohjeet lääkemuutoksista ja luento lääkkeiden vaikutuksista kaatumisvaaraan, vähensi säännöllisten psyykenlääkkeiden käyttäjien lukumäärää 22 % ja bentsodiatsepiineja tai niiden kaltaisia lääkkeitä käyttävien lukumäärää 35%. Kaatumisen vuoksi terveyskeskukseen ja keskussairaalaan hakeutuneiden iäkkäiden kaatumisvaaratekijöiden selvittelyyn ja uusien kaatumisten tai murtumien ehkäisyyn kiinnitettiin erittäin vähän huomiota. Toimenpiteet keskittyivät syntyneiden vammojen tutkimiseen ja hoitoon. Monitekijäinen ehkäisyinterventio vähensi masentuneiden ja monikaatuilijoiden kaatumisia, mutta ei kaikkien osallistujien kaatumisten määrää 12 kuukauden ehkäisyohjelman aikana. Erityisesti bentsodiatsepiiniryhmän lääkkeitä käyttävät verrokkiryhmän jäsenet joutuivat herkemmin kaatumisen vuoksi lääkärinhoitoon ehkäisyohjelman jälkeisen vuoden aikana kuin nämä lääkkeet lopettaneet koeryhmän jäsenet. Johtopäätöksenä voidaan todeta, että psyykenlääkkeiden tunnistaminen kaatumisten vaaratekijäksi oli puutteellista. Niiden käyttöön tulisi kiinnittää enemmän huomiota, ja niiden käyttö tulisi purkaa aina, kun se on lääketieteellisesti mahdollista. Kaatumisten ehkäisy pitäisi kuulua terveydenhoitoon. Kohdennettuja ehkäisyohjelmia erilaisille kaatumisvaarassa oleville iäkkäille tulee kehittää edelleen.

Benzodiazepines and Cognitive Functioning in Older Adults. With Emphasis on Long-Term Use and Withdrawal

Benzodiazepines (BZD) and benzodiazepine related drugs (RD) are the most commonly used psychotropics among the aged. The use of other psychotropics taken concomitantly with BZD/ RD or their cognitive effects with BZD/RD have not been studied frequently. The aim of this academic thesis was to describe and analyse relationships between the use of BZD/RD alone or concomitantly with antipsychotics, antidepressants, opioids, antiepileptics, opioids and anticholinergics in the aged and their health. Especially, the relationships between long-term use of BZD/RD and cognitive decline were studied. Additionally, the effect of melatonin on BZD/RD withdrawal and the cognitive effects of BZD/RD withdrawal were studied. This study used multiple data sets: the first study (I) was based on clinical data containing aged patients (≥65 years; N=164) admitted to Pori City Hospital due to acute disease. The second data set (Studies II and III) was based on population-based data from the Lieto Study, a clinico-epidemiological longitudinal study carried out among the aged (≥65 years) in the municipality of Lieto. Follow-up data was formed by combining the cohort data collected in 1990-1991 (N=1283) and in 1998-1999 (N=1596) from those who participated in both cohorts (N=617). The third data set (Studies IV and V) was based on the Satauni Study’s data. This study was performed in the City of Pori in 2009-2010. In the RCT part of the Satauni Study, ninety-two long-term users of BZD/RD were withdrawn from their drugs using melatonin against placebo. The change of their cognitive abilities was measured during and after BZD/ RD withdrawal. BZD/RD use was related to worse cognitive and functional abilities, and their use may predict worse cognitive outcomes compared with BZD/RD non-users. Hypnotic use of BZD/RD could be withdrawn with psychosocial support in motivated participants, but melatonin did not improve the withdrawal results compared to those with placebo. Cognitive abilities in psychomotor tests did not show, or showed only modest, improvements for up to six months after BZD/RD withdrawal. This suggests that the cognitive effects of BZD/RD may be longlasting or permanent.

Noroviruses associated with acute gastroenteritis in a children's day care facility in Rio de Janeiro, Brazil

Noroviruses (Norwalk-like viruses) are an important cause of gastroenteritis worldwide. They are the most common cause of outbreaks of gastroenteritis in the adult population and occur in nursing homes for the elderly, geriatric wards, medical wards, and in hotel and restaurant settings. Food-borne outbreaks have also occurred following consumption of contaminated oysters. This study describes the application of a reverse transcription-polymerase chain reaction (RT-PCR) assay using random primers (PdN6) and specific Ni and E3 primers, directed at a small region of the RNA-dependent RNA polymerase-coding region of the norovirus genome, and DNA sequencing for the detection and preliminary characterisation of noroviruses in outbreaks of gastroenteritis in children in Brazil. The outbreak samples were collected from children <5 years of age at the Bertha Lutz children's day care facility at Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, that occurred between 1996 and 1998, where no pathogen had been identified. At the Bertha Lutz day care center facility, only Fiocruz's employee children are provided for, and they come from different social, economic and cultural backgrounds. Three distinct genogroup II strains were detected in three outbreaks in 1997/98 and were most closely related to genotypes GII-3 (Mexico virus) and GII-4 (Grimsby virus), both of which have been detected in paediatric and adult outbreaks of gastroenteritis worldwide.

Aging policy: a case study of co-ordination in Canadian governments

ABSTRACT Canada is an aging society. The number of people aged sixty-five and over is rising, while the number of people under twenty is declining. These two concurrent changes in the age structure have produced a sh~ft in the demographic composition of Canada which is commonly referred to as the aging phenomenon. Regardless of whether or not the number of people under twenty continues to decline, the number of elderly in Canada will almost double over the next twenty years. This rapidly growing elderly clientele will doubtless have an impact on Canadian governments. Federal, provincial and municipal governments are presently providing a variety of programs that have a special bearing on the aged and most senior citizens are beneficiaries of one or more of these programs. The ramifications of a rapidly growing elderly clientele are obvious. In order to cope with the impact of a significant increase in the number of elderly persons, the development and implementation of aging policy must be co-ordinated at each level of government and between and among levels of government. If aging policy is not co-ordinated, the results are likely to be: inappropriate policy decisions; duplication and overlap; and, ineffective and irresponsive services. No one benefits from these results. The need for co-ordination is apparent. The purpose of this thesis is to examine existing governmental efforts to co-ordinate policy in the field of aging. These efforts are examined by focusing on interactions directed at co-ordination between and among major actors in aging policy. A framework is used to structure the description and analysis of these interactions. The variables of formalisation and intensity and the concept of power are instrumental in analysing interactions for co-ordination. The underlying intent of this thesis is to discover some of the main gaps in existing governmental efforts to co~ordinate aging policy. Gaps are, in fact, discovered. Several explanations for the existence of gaps in interactions for co-ordination are discussed. A major hypothesis involving a relationship between a bureaucratic form of organisation and interactions for coordination is suggested. Finally, three recommendations for improving co-ordination in aging policy are offered.

Residence of William W. Kitchen & Residence of Charles Kitchen - Vignette

A vignette two homes in Grimsby. There are two homes in the image, one the residence of William W. Kitchen, the second the residence of Charles Kitchen.

La capacité d'action collective des populations marginalisées dans le cadre des stratégies de lutte pour la reconnaissance : les cas de Cité de l'Éternel à Port-au-Prince (Haïti) et de la Sierra Santa Catarina (Mexico)

Cette thèse analyse la capacité d’action collective des populations marginalisées situées respectivement dans un bidonville appelé Cité de l’Éternel à Port-au-Prince (Haïti) et dans des campements à la Sierra Santa Catarina, Iztapalapa (Mexico). À Port-au-Prince, avant la chute de la dictature des Duvalier, des «tontons macoutes» envahirent un terrain situé en bordure du quai de la capitale, près du boulevard Harry Truman. Après s’y être installés, ils ont procédé à la vente de parcelles destinées à la construction de logement à des particuliers. Mais après la chute de Jean-Claude Duvalier, en 1986, des gens de la populace en ont profité pour envahir ce qui restait de ces terrains marécageux. Après l’occupation, ils se sont organisés pour défendre collectivement leur propriété avant d’entreprendre, par la suite, des démarches pour y amener des services et obtenir la régularisation de leur situation sur ces territoires. À la Sierra Santa Catarina, des populations conduites par des militants d’un Front populaire ont occupé des terrains situés au pied d’une montagne de sable afin d’accéder à la propriété et de construire leur demeure. À l’instar des populations de la Cité, ces gens se sont organisés pour aménager des espaces, y ériger des logements provisoires, monter la garde afin de ne pas être déguerpis par les forces de police. Tout en travaillant pour accéder à leur manière aux services de base, elles entreprennent des actions auprès des institutions publiques afin d’obtenir la régularisation de leur situation. Par rapport à la capacité d’action collective de ces populations, les théories sociologiques sont divisées. D’un côté, certains auteurs soutiennent la thèse de l’incapacité de ces populations d’avoir des intérêts collectifs et d’agir en conséquence. Selon eux, sans une médiation sociale ou à défaut d’une agrégation et d’une représentation politiques, ces populations sont incapables d’avoir une subjectivité collective. De l’autre, des auteurs pensent qu’à partir des liens d’amitié de parenté et de voisinage, indépendamment de leurs situations socioéconomiques, ces populations peuvent créer des stratégies de subsistance et de luttes qui leur permettent de trouver des solutions à des problèmes tant individuels que collectifs. S’agissant des populations qui envahissent des terrains en milieu urbain pour habiter, les actions de ces gens là sont définis déjà comme une forme d’action collective inscrite dans des rapports sociaux qui se caractérisent par la différenciation entre les groupes sociaux dans l’accès à la propriété. Ainsi, leurs revendications de reconnaissance et de régularisation auprès des instances étatiques sont déterminées par leur mode d’accès aux biens et aux richesses inégalement réparties en Haïti et au Mexique. Les populations des deux territoires ont entrepris diverses démarches auprès de certaines institutions et réalisé des actions collectives soit pour amener des services de base tels que l’eau et l’électricité, soit pour obtenir de l’État la reconnaissance des territoires envahis, c’est-à-dire leur jonction à la cartographie de la ville. Cette reconnaissance implique non seulement l’installation des services réguliers au bénéfice de la population mais aussi l’octroi à chaque propriétaire de son titre de propriété. Si dans le cas de la Sierra Santa Catarina les démarches sont entreprises auprès des institutions publiques, dans celui de Port-au-Prince, ce sont les ONG ou les agence de coopération qui sont touchées et qui fournissent certains services à la population conformément à la priorité de leurs bailleurs de fonds. Les interventions auprès de l’État se font plutôt dans le but d’obtenir une autorisation de fonctionnement d’une association locale. Il ressort des approches théoriques et des actions collectives réalisées par ces populations qu’on ne peut pas dire qu’elles sont incapables d’avoir une subjectivité collective et des intérêts communs sans une agrégation et une représentation politique. À partir de différents liens entre les individus, des associations sont créées lesquelles permettent d’établir une médiation entre les populations et d’autres organismes. Dans le cas des campements, les actions collectives sont certainement mises à contribution par quelques leaders. Cela participe de toute une tradition politique au Mexique. Néanmoins, dans certains campements, des populations parviennent à tenir tête jusqu’à révoquer certains leaders. Au-delà de leur situation socioéconomique, de l’emprise de certains dirigeants de campement, de l’indifférence de l’État (dans le cas de Port-au-Prince, notamment), ces populations font preuve d’une étonnante capacité critique de leur situation tant dans leurs relations avec les dirigeants des associations et des campements que par rapport à l’État. Ceci pourrait soulever des doutes quant à la possibilité qu’elles soient réellement ou inconsciemment manipulées. Cela suggère la possibilité d’actions collectives autonomes de portée critique là où les circonstances le permettent Mots clés : Marginalisation, action collective, reconnaissance, Débrouille, capacité critique, bidonvilles, instrumentalisation politique, reconnaissance fragmentée.

Étude des mécanismes associés aux effets bénéfiques de la restriction calorique sur la fonction somatotrope du rat vieillissant.

Dans les cellules somatotropes, la liaison du facteur de libération de l’hormone de croissance (GHRH) à son récepteur (GHRH-R) stimule la synthèse et la sécrétion de l’hormone de croissance (GH) ainsi que la prolifération cellulaire. Chez les mammifères, le vieillissement est caractérisé par une diminution de la sécrétion de GH, liée à une perte de sensibilité des somatotropes au GHRH. Chez le rat âgé, des modifications de niveaux d'ARNm du GHRH-R et une diminution d'affinité et de capacité de liaison du GHRH sont rapportés. Au cours du vieillissement, une augmentation des niveaux de glucose et d’acides gras libres sérique suggère qu’une gluco- ou lipotoxicité puisse contribuer au dysfonctionnement de la fonction somatotrope. À ce jour, la restriction calorique modérée de longue durée (RCMLD) constitue l’intervention la plus efficace pour prévenir ou retarder les détériorations liées à l’âge. Des études ont montré des effets bénéfiques de la RCMLD sur l’axe somatotrope au cours du vieillissement via un maintien des paramètres de liaison du GHRH-R. Compte tenu de l’importance de cet axe, la compréhension des mécanismes menant à la somatopause ainsi que ceux associés aux effets bénéfiques de la RCMLD s’avère importante. Les objectifs principaux de la présente thèse étaient : 1) de déterminer les effets de la RCMLD chez le rat, sur le GHRH-R hypophysaire et la sensibilité des somatotropes au GHRH, 2) d’identifier les mécanismes associés à la somatopause et aux effets bénéfiques de la RCMLD, et 3) de préciser les effets d’une gluco-ou lipotoxicité sur l’axe somatotrope de rats et leur implication dans la somatopause. Des rats de 8 mois ont été soumis à une restriction calorique de 40% jusqu’à l’âge de 18-20 mois et ont été comparés à des rats jeunes et âgés nourris ad libitum. Cette étude a permis de mettre en évidence des effets bénéfiques de la RCMLD sur la régulation et la fonctionnalité du GHRH-R et de proposer que le glucose et les acides gras libres (AGL) circulants soient impliqués dans le vieillissement de la somatotrope. Une étude de micro-puce à ADN à permis d’identifier des gènes associés à des mécanismes de protection et de réparation des dommages cellulaires mis en place dans l’hypophyse antérieure au cours du vieillissement et par la RCMLD. Finalement, les effets d’un stress gluco- ou lipotoxique sur la fonction somatotrope ont été étudiés chez des rats de 2 et 6 mois, infusés 72 h avec une solution de glucose ou d’Intralipides, mimant les niveaux circulants de glucose et d’AGL retrouvés chez le rat âgé. Les résultats obtenus montrent que la glucotoxicité affecte la régulation de certains gènes de la somatotrope, dont le GHRH-R, et suggèrent que la capacité de réponse à ce type de stress est altérée. Les mécanismes par lesquels la glucotoxicité exerce ces effets pourraient inclure la génération de stress oxydant. L’ensemble de ces résultats proposent de nouvelles pistes mécanistiques qui pourraient contribuer au retardement de la somatopause et, ultimement, à l’élaboration de nouvelles stratégies d’intervention nutritionnelles ou pharmacologiques ciblant les mêmes voies que la RCMLD, avec une efficacité similaire ou supérieure.