Submitted by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-20T21:43:39Z No. of bitstreams: 2 Dissertação Cristiane Pereira.pdf: 1114775 bytes, checksum: 2a455906de543e8e5836442a98096bc7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-21T00:04:47Z (GMT) No. of bitstreams: 2 Dissertação Cristiane Pereira.pdf: 1114775 bytes, checksum: 2a455906de543e8e5836442a98096bc7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2015-03-21T00:05:04Z (GMT) No. of bitstreams: 2 Dissertação Cristiane Pereira.pdf: 1114775 bytes, checksum: 2a455906de543e8e5836442a98096bc7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-03-21T00:05:04Z (GMT). No. of bitstreams: 2 Dissertação Cristiane Pereira.pdf: 1114775 bytes, checksum: 2a455906de543e8e5836442a98096bc7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / A Restrição Calórica (RC) tem sido associada a inúmeros benefícios à saúde, como redução do peso e gordura corporal, melhora no perfil lipídico e aumento de enzimas antioxidantes que resultam na prevenção de diversas doenças, como as cardiovasculares (DCV) e na prevenção e atenuação de doenças neurodegenerativas relacionadas à idade em diversas espécies animais. No entanto, há poucos estudos que avaliam o impacto da RC iniciada em ratos jovens comparada com a iniciada em ratos adultos e sobre diferentes períodos de tratamento. O presente estudo avaliou o estado nutricional e metabólico, risco cardiovascular (CV) associado ao perfil lipídico sérico, parâmetros comportamentais e oxidativos em ratos Wistar submetidos à intervenção nas fases de vida jovem e adulta. Ratos com 40 ou 70 dias de vida foram alimentados ad libitum ou submetidos à RC por 12 ou 16 semanas. Nossos resultados mostraram que o peso corporal (PC) dos ratos submetidos à RC foi inferior – 21% nos jovens e 16% nos adultos, comparados aos controles (p<0,05). Os parâmetros bioquímicos séricos avaliados indicaram bom estado de saúde. Após 12 semanas, a RC diminui o colesterol total (CT), HDL, o colesterol não-HDL e a razão LDL/HDL nos ratos jovens e triacilglicerois (TG) e razão TG/LDL nos adultos – neste último com aumento de LDL e da razão LDL/HDL (p<0,05). O prolongamento da intervenção não resultou em mudança do risco CV associado ao perfil lipídico sérico. A atividade da paraoxonase 1 (PON1) foi mantida com a RC e a maior relação PON1/HDL foi encontrada nos jovens submetidos à RC por 12 semanas (p<0,05). Após 12 semanas, no hipocampo, a RC aumentou os níveis de glutationa (GSH) nos jovens e diminuiu a produção de espécies reativas de oxigênio (ERO) e peroxidação lipídica nos adultos, comparados aos controles (p<0,05). A GSH e a atividade da glutationa peroxidase (GPx) parecem aumentar com a idade independente do tratamento. Nenhuma alteração foi observada na memória, na atividade da superóxido dismutase (SOD) e na produção de óxido nítrico (ON). A idade per se não ocasionou diferenças nos parâmetros de estresse oxidativo avaliados. Este estudo indica que a RC iniciada precocemente e mantida por 12 semanas proporcionou redução do risco CV associado ao perfil lipídico sérico quando comparada a iniciada na fase adulta. Já seu prolongamento não manteve esse efeito benéfico. A atividade da PON1 foi mantida com a RC independentemente da idade de início e do tempo de tratamento. Ainda, a RC resultou em melhora significativa de parâmetros celulares de autodefesa do hipocampo, tanto iniciada em jovens, quanto na fase adulta. Contudo, a RC iniciada em ratos jovens alterou de forma positiva e expressiva um importante tampão redox do hipocampo. / Caloric restriction (CR) has been associated to numerous health benefits such as weight and body fat reduction, lipid profile improvement and increased antioxidant enzymes that result in prevention of various diseases such as cardiovascular disease (CVD) and prevention and attenuation of age-related neurodegenerative diseases in several animal species. However, there are few studies that assess the impact of CR initiated in young rats compared with adult rats and started in on different treatment periods. The present study evaluated the nutritional and metabolic status, cardiovascular (CV) risk associated with serum lipid profile, behavioral and oxidative parameters in Wistar rats subjected to intervention in young and adult phases of life. Rats with 40 or 70 days old were fed ad libitum or subjected to CR for 12 or 16 weeks. Our results showed that CR-fed rats had lower body weight (BW) - 21% in young rats and 16% in adults rats compared to controls (p<0.05). The serum biochemical parameters indicated good health. After 12 weeks, in hippocampus, the CR decreases total cholesterol (TC), HDL, non-HDL cholesterol and LDL/HDL ratio in young rats and triacylglycerols (TG) and TG/LDL ratio in adults - the latter with increased LDL and LDL/HDL ratio (p<0.05). The extension of the intervention resulted in no change in CV risk associated with serum lipid profile. Paraoxonase 1 (PON1) activity was maintained with CR and PON1/HDL highest ratio was found in young rats underwent CR for 12 weeks (p<0.05). After 12 weeks, the CR increased glutathione (GSH) levels in young rats and decreased reactive oxygen species (ROS) production and lipid peroxidation in adult rats compared to controls (p<0.05) GSH and glutathione peroxidase (GPx) activity seem to increase with age regardless of treatment. No change was observed in memory, superoxide dismutase (SOD) activity and nitric oxide (NO) production. Age per se did not cause differences in oxidative stress parameters evaluated. This study indicates that CR maintained for 12 weeks resulted in an reduction CV risk associated with serum lipid profile when initiated in young rats compared to initiated in adulthood. The extension has not kept this beneficial effects. PON1 activity was maintained with CR regardless the age at onset and treatment time. Still, CR resulted in a significant improvement in hippocampus cellular self-defense parameters, both begun in youth, as in adulthood. However, the CR initiated in young rats changed positively and significantly an important hippocampus redox buffer.

La suralimentation postnatale (SAPN) chez les rongeurs induit des modifications cardio-métaboliques à l'âge adulte. Notre objectif a été de déterminer si une restriction calorique (RC) modérée pouvait restaurer ces altérations cardio-métaboliques et améliorer la récupération post-ischémique dans un modèle de cœur perfusé in vitro.Après la naissance, des souriceaux C57BL/6 ont été répartis au nombre de 9 par portée pour les groupes témoins (Normoalimentées: NA), ou au 3 par portée pour induire la SAPN. Après le sevrage, les souris ont eu un accès libre à une nourriture standard et à l’eau. A 6 mois, la moitié des souris des deux groupes a été soumise à une RC de 20% (NARC, SARC) pendant un mois, tandis que l’autre moitié a continué à se nourrir ad libitum (NAAL, SAAL). Des paramètres métaboliques et de la fonction cardiaque ont été évalués avant et après RC. A 7 mois, nous avons évalué au niveau du myocarde la sensibilité aux lésions d'ischémie-reperfusion et le niveau stress oxydant cardiaque. Les souris SAPN adultes présentent un surpoids, une accumulation de graisses, une hyperleptinemie, une intolérance au glucose, une résistance à l’insuline, ainsi qu’une diminution de la fraction d'éjection ventriculaire gauche (FEVG). Après un mois de RC, le poids corporel de SARC est revenu à la normale bien que ni la masse grasse ni la leptinémie n’aient diminué. Nous avons noté une amélioration du métabolisme au glucose et de la FEVG chez les souris SARC. Sur cœur isolé perfusé après 30 min d'ischémie globale, la taille de l'infarctus des souris SARC est la plus faible. La RC est associé à une amélioration de la fonction de la chaine respiratoire mitochondriale chez les souris SARC et à une diminution de la production des radicaux libres. Cependant, les effets bénéfiques de la RC n’ont pas été retrouvés pour la plupart des paramètres mesurés chez les souris NARC. Notre étude a confirmé le rôle de la programmation de SAPN sur la fonction cardio-métabolique. Une RC modérée, à court terme, permet de diminuer le poids corporel, mais aussi d’améliorer le métabolisme du glucose, d’améliorer la fonction cardiaque et de diminuer la susceptibilité aux lésions d'ischémie-reperfusion chez les souris SAPN. / Postnatal overfeeding (PNOF) in rodents induces early programming of cardio-metabolic risk. Our aim was to determine if a moderate diet restriction could restore cardio-metabolic alterations induced by PNOF.Immediately after birth, litters of C57BL/6 mice were either maintained at 9 (normal litter, NL), or reduced to 3 (small litter, SL) to induce PNOF. At weaning, all mice received a standard diet ad libitum (AL). At 6 month of age, half of the NL and SL mice were assigned to a moderate 20% calorie restriction (CR: NLCR, SLCR) for one month, while the other mice continued to eat AL (AL: NLAL, SLAL). Glucose and insulin tolerance tests, cardiac function (echocardiography), body composition (Echo-MRI), cardiac sensitivity to ischemia-reperfusion injury, mitochondrial function, reactive oxygen species (ROS) generation (EPR spectroscopy) and insulin signaling were assessed before and/or after one month of CR.Adult SL mice presented overweight, fat accumulation, hyperleptinemia, glucose intolerance, insulin resistance and decreased left ventricular ejection fraction (LVEF). After one month of moderate CR, body weight of SLCR was normalized to this of NLAL however their fat mass and leptinemia were not decreased. Glucose metabolism was improved and LVEF was increased In SLCR. After 30 min of global ischemia, hearts isolated from SLCR mice showed better recovery and smaller infarct size than this of others groups. CR increased the cardiac mitochondrial respiratory rate in SLCR mice whereas cardiac ROS production was significantly decreased in SLCR mice. Insulin signaling in heart was affected neither by PNOF nor by CR. Intriguingly, no difference was observed in NLCR mice for most of the parameters investigated.Our results confirmed the programming of early overfeeding on metabolic and cardiac function. A short-term moderate CR in not only normalized body weight in SL mice but also ameliorate the metabolic programming and reverse the cardiac dysfunction induced by PNOF.

One of the greatest risk factors for disease is advanced age. As the human lifespan has increased, so too have the burdens of caring for an increasingly older population suffering from rising rates of cardiovascular disease, kidney disease, diabetes, and dementia. The need for improving medical technology and developing new therapies for age-related diseases is manifest. Yet our understanding of the processes of aging and how to attenuate the effects of aging remains incomplete. Various studies have established calorie restriction as a robust method for extending lifespan in laboratory organisms; however the mechanism is a topic of much debate. Advancing our understanding of calorie restriction holds promise for illuminating biochemical processes involved in the aging process. One of the best explanations for the lifespan extension benefits of calorie restriction is that it improves cellular protein homeostasis (proteostasis), but because proteostasis is dynamic, it can be difficult to measure. We developed a novel combined omics methodology integrating kinetic proteomics, and applied it to a mouse model placed on calorie restriction. Our unbiased approach integrating just three measurements (kinetic proteomics, quantitative proteomics, and transcriptomics) enabled us to characterize the synthesis and degradation of thousands of proteins, and determine that calorie restriction largely alters proteostasis by slowing global protein synthesis post-transcriptionally. Validating our omics approach, we were able to replicate many previous results found in the literature, demonstrating the differential regulation of various protein ontologies in response to the nutrient stress of calorie restriction. Moreover, we were able to detect differential degradation of the large and small ribosomal subunits under calorie restriction, and proposed a model in which the rate of protein synthesis could be attenuated by the depletion of the large ribosomal subunit relative to the small subunit. The flexibility of our dynamic combined omics approach was demonstrated by the expansion of measurements to include nucleic acids and lipids. Flux measurements of DNA, ribosomal RNA, and lipids yielded cellular division rates, ribosome turnover, and lipid metabolism insights, respectively. We also adapted this approach to two-dimensional tissue imaging by DESI-MS in a proof-of-concept study to demonstrate its utility for studying regional differences in metabolism. The future integration of metabolomics and lipidomics into our combined omics approach would be facile, and add unprecedented depth to systems-wide studies involving cellular metabolism. Applied to the regulation of cellular homeostasis in humans, this has the potential to open new avenues for elucidating the etiology of aging, understanding the pathology of age-related diseases, and identifying novel targets for therapeutics.

Adipogenesis and ectopic lipid accumulation during aging have a great impact on the aging process and the pathogenesis of chronic diseases with age. However, at present, information on the age-related molecular changes in lipid redistribution patterns and their potential nutritional interventions is sparse. We investigated the mechanism underlying age-related lipid redistribution and its modulation using 5-, 17-, and 24-month-old male Fischer 344 rats fed ad libitum (AL) or a 3-week-long CR (40% less than AL) diet. Results revealed that the activities of adipogenic transcription factors were decreased in the white adipose tissue (WAT) of aged AL rats. In contrast, the skeletal muscle of aged AL rats showed increased fat accumulation through decreased carnitine palmitoyltransferase-1 activity, which was blunted by short-term CR. This study suggests an age-related shift in lipid distribution by reducing the adipogenesis of WAT while increasing intramyocellular lipid accumulation, and that CR can modulate age-related adipogenesis and ectopic lipid accumulation.

No description available.

The important factor in regulation of metabolic processes is regulatory proteins, which are able to react by feed-back to energetic state of the cell. Big attention is focused on the AMP activated kinase (AMPK) and NAD+ activated deacetylase SIRT1. These enzymes interact together and their stimulation increases mitochondrial biogenesis and fatty acid oxidation. Due to this it functions beneficially against the onset of obesity, insulin resistance and ageing. Fasting, exercise and some antidiabetogenic drugs act by these regulators. n-3 polyunsaturated fatty acids (PUFA) are also known because of their stimulative effects on mitochondrial biogenesis and -oxidation. Previous work of our group have showed that intake of higher dose of n-3 polyunsaturated fatty acids (PUFA) in diet lead to increase in activity of AMPK in white adipose tissue. New results presented in this thesis show that SIRT1 is essential for increase in expression of stimulators of -oxidation (PPAR etc) in response to n-3 PUFA in diet. n-3 PUFA futher improve the metabolic profile synergistically with calorie restriction probably through SIRT1.

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Aujourd’hui la restriction calorique modérée et chronique (RC) est la seule intervention non génétique capable de ralentir l’apparition de pathologies liées à l’âge et d’accroître la longévité chez plusieurs espèces animales. Le resvératrol (RSV), un composé appartenant au groupe des polyphénols, présente des propriétés thérapeutiques intéressantes et constitue un candidat prometteur comme mimétique des effets d’une RC. Afin d’évaluer l’impact de tels protocoles nutritionnels à long terme, une étude longitudinale a été menée sur une cohorte de 53 mâles microcèbes (Microcebus murinus), modèle primate pertinent pour les recherches sur le vieillissement normal ou pathologique au vue de sa longévité maximale de 12 ans en captivité. Depuis l’intégration des animaux dans l’étude (3 ans d’âge) à l’avancement actuel du projet (8 ans d’âge), des paramètres physiologiques et comportementaux ont été évalués régulièrement au sein de la cohorte, partagée en trois groupes: un groupe soumis à une RC (-30%) et un groupe supplémenté en RSV (200 mg.kg-1.jour-1), comparés à un groupe contrôle (CTL). Avec l’âge, chez les microcèbes CTL, des perturbations sont apparues : diminution de la sensibilité à l’insuline, accumulation de dommages cellulaires, déclin moteur et cognitif (mémoire spatiale de reférence) et déclin de certains marqueurs prédictifs du vieillissement chez cette espèce. La RC a permis une amélioration de la sensibilité à l’insuline et a limité l’accumulation de certains marqueurs du stress oxydant, elle n’a pas entraîné d’amélioration des capacités cognitives, mais a diminué l’anxiété, amélioré les performances motrices et augmenté l’activité locomotrice spontanée. La RC a aussi induit une réponse adaptative métabolique avec une perte de masse corporelle sans réduire les dépenses énergétiques, un abaissement des taux hormonaux d’IGF-1 et de la testostérone suggérant un compromis entre reproduction et survie. Le RSV a mimé une partie des effets bénéfiques démontrés sous RC. Cependant il a permis une amélioration de la mémoire spatiale de travail, absente chez les animaux restreints. Le RSV a également montré des effets opposés à ceux de la RC comme un maintien de la masse corporelle et des taux d’hormones par rapport aux CTL, une augmentation des dépenses énergétiques et des niveaux de testostérone pendant la période de jours longs. Finalement les données de survie actuelles sont prometteuses ; moins de 50% de l’effectif de départ des animaux CTL a survécu, alors que plus de 50% des animaux RC et RSV sont encore vivants, présentant de surcroît un âge moyen à la mort plus élevé d’environ 1 an par rapport aux CTL. Malgré des effets hétérogènes et pourtant bénéfiques, la RC et le RSV sont capables de ralentir l’apparition de certains déclins intrinsèques au vieillissement et d’améliorer la survie des microcèbes, soutenant l’hypothèse selon laquelle ces effets pourraient être induits par des mécanismes différents mais permettant d’atteindre les mêmes issues favorables notamment au niveau de l’espérance de vie. Ces résultats constituent un véritable outil pour la compréhension future des mécanismes sous-jacents au processus du vieillissement mais aussi des voies de régulation cellulaires mises en jeu par la RC et le RSV à moyen et long terme chez un primate / Nowadays moderate and chronic calorie restriction (CR); is the only non-genetic intervention known to slow the onset of age-related diseases and to increase longevity in several animal species. Resveratrol (RSV), a natural compound belonging to the polyphenols group, has therapeutic properties and is a promising candidate as CR effects mimetic. To assess the impact of such long-term nutritional protocols, a longitudinal study was conducted on a cohort of 53 males grey mouse lemurs (Microcebus murinus), a relevant primate model for normal and pathological aging research as regards to its high longevity in captivity, up to 12 years. Since the integration of the animals in the study (3 years old) to the current status of the project (8 years of age), physiological and behavioral parameters were assessed regularly in the cohort divided into three groups: a group submitting to a -30% CR and a group supplemented with RSV (200 mg.kg-1.day-1), compared to a control group (CTL). With age, disturbances appeared in CTL mouse lemurs: decreased insulin sensitivity, accumulation of cellular damage, motor and cognitive decline associated with particular type of memory and a decline of certain predictive biomarkers of aging in this species. CR has improved insulin sensitivity and limited the accumulation of markers of oxidative stress, it has not resulted in improved cognitive abilities but in a decreased anxiety, improved motor performances and an increased spontaneous locomotor activity. CR also induced an adaptive metabolic response with body weight loss without lowering energy expenditure, lower hormone levels of IGF-1 and testosterone, supporting a probable trade-off between reproduction and survival. RSV mimicked some of the beneficial effects demonstrated in CR. However, it has improved the spatial memory task, which was not observed in restricted animals. RSV also showed opposite effects to those of CR, as maintained body weight and hormone levels compared to CTL, an increase in energy expenditure and in testosterone levels during the long day’s season. Finally, the current survival data are promising; less than 50% of the CTL animals survived, while more than 50% of CR and RSV animals are still alive, with in addition a mean age at death about 1 year higher compared with CTL animals. Despite heterogeneous, but yet beneficial effects, CR and RSV were able to slow the appearance of some intrinsic age-related declines and to improve the lemurs’ survival, supporting the hypothesis that these effects may be mediated by different mechanisms achieving the same positive outcomes including enhanced life expectancy. These evidences are a real tool for the future understanding of the mechanisms underlying the aging process but also of cellular regulatory pathways that are involved in long term CR and RSV treatment in a primate