The cost of reproduction (CoR) is a central mechanism in the evolution of species' life-history t... more The cost of reproduction (CoR) is a central mechanism in the evolution of species' life-history traits. Because acquired resources are finite, fitness is maximized for an optimal balance between the allocation to current fecundity versus the allocation to survival and future reproduction (Cody, 1966; Reznick, 1985; Stearns, 1989; Williams, 1966). This has proved a robust theory for explaining the difference in life-history strategies within and between clades (e.g.,Charnov, 2002; Linden & Møller, 1989). Within species however, the role played by CoR in generating variance in individuals' life trajectories is yet largely unknown. Experimental procedures-such as artificially increasing reproductive load-generally succeed to evidence costs (see in Boonekamp, Salomons, Bouwhuis, Dijkstra, & Verhulst, 2014; reviewed in Santos & Nakagawa, 2012). But evidencing CoR from longitudinal demographic data has proved difficult. It is particularly the case for evidencing survival CoR (rather than reproductive CoR as in Kroeger, Blumstein, Armitage, Reid, & Martin, 2018) and long-term CoR (rather than short-term CoR as in Froy,
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
To study the temporal organization of daily hypothermia and torpor in a nocturnal Malagasy primat... more To study the temporal organization of daily hypothermia and torpor in a nocturnal Malagasy primate, the gray mouse lemur, body temperature (Tb) and locomotor activity were recorded using telemetry on 39 males held in 24-h light-dark cycles of different photoperiods. Under free-running condition, the circadian Tb and locomotor activity rhythms had a period shorter than 24 h. Circadian daily hypothermia started by a rapid drop in Tb (0.24°C/10 min) at the end of subjective night (13 h 25 ± 20 min) and was characterized by minimal Tb values 3 h 20 ± 5 min later. Spontaneous arousal from daily hypothermia occurred at a fixed time (6 h 05 ± 15 min, n = 7) after the beginning of subjective day. In animals exposed to 24-h light-dark cycles with night duration varying from 10 to 14 h, locomotor activity was strictly restricted to dark time, but the temporal organization of daily hypothermia was not modified, although changes in amplitude of Tb rhythm were observed. Daily hypothermia was dir...
Ageing results from the accumulation of multifactorial damage over time. However, the temporal di... more Ageing results from the accumulation of multifactorial damage over time. However, the temporal distribution of this damage remains unknown. In seasonal species, transitions between seasons are critical periods of massive physiological remodelling. We hypothesised that these recurrent peaks of physiological remodelling are costly in terms of survival. We tested whether captive small primates exposed to an experimentally increased frequency of seasonal transitions die sooner than individuals living under natural seasonality. The results show that experiencing one additional season per year increases the mortality hazard by a factor of 3 to 4, whereas the expected number of seasons lived is only slightly impacted by the seasonal rhythm. These results demonstrate that physiological transitions between periods of high and low metabolic activity represent a major mortality risk for seasonal organisms, which has been ignored until now.
INTRODUCTION With the progressive aging of the World population, an increasing number of people s... more INTRODUCTION With the progressive aging of the World population, an increasing number of people suffer from cognitive impairment and dementia. These deficits affect quality of life and cause social, economic and public health problems [1-3]. A clear relationship has been established between age-associated cognitive decline and selective regional brain atrophy from normal aging to dementia [4-5]. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. Middle-aged metabolic disorders [6-8] culminating in type 2 diabetes (T2D) [9-11] could be a risk factor to memory impairment and cerebral atrophy. T2D is characterized by hyperglycaemia (> 7mmol/L), impairment of glucose tolerance leading to insulin resistance [12]. Patients with type 2 diabetes display memory impairment [9-11] and anatomic brain alterations including hippocampus www.aging-us.com
Mammals use variations in the length of day to anticipate environmental changes and time their re... more Mammals use variations in the length of day to anticipate environmental changes and time their reproduction. Light pollution, which affects day length perception, could lead to changes in biological functions. To explore the effects of light pollution on seasonal reproduction, we conducted an experimental study on a strict long-day breeder, the nocturnal gray mouse lemur (Microcebus murinus). Twelve females were randomly exposed to either a moonlight treatment or a light pollution treatment for 5 weeks during the transition from a short-to long-day photoperiod. Daily rhythms of locomotor activity and core temperature were recorded, and the occurrence of estrus and urinary 17-β-estradiol concentrations were monitored. In females exposed to light pollution, the first seasonal estrus occurred while they were still in a short-day photoperiod, 2 weeks earlier than in females exposed to moonlight. Moreover, the daily rhythms profiles of females exposed to light pollution showed significant changes that mimicked long-day acclimatization. This study demonstrates that light pollution can affect daily rhythms and the timing of seasonal estrus in a primate and suggests that functional changes in the circadian system may underlie the adverse effects of light pollution that are observed in wildlife.
-Au cours du vieillissement, la capacité des organismesà s'adapterà leur environnement est altéré... more -Au cours du vieillissement, la capacité des organismesà s'adapterà leur environnement est altérée. Chez l'Homme, les troubles liésà l'âge incluent l'apparition de perturbations des rythmes biologiques, notamment des rythmes veille/sommeil, des rythmes de température corporelle et de sécrétion d'hormones. L'altération des rythmes biologiques avec l'âge peut avoir des conséquences majeures sur la santé, notamment du fait de l'altération des rythmes veille-sommeil qui entraîne une forte altération de l'état général des individus. L'étude de ces altérations constitue de ce fait un enjeu de santé majeur et nécessite l'utilisation de modèles animaux appropriés, tels que le microcèbe (Microcebus murinus), un petit primate malgache aux rythmes biologiques très prononcés.
Caloric restriction (CR) is the only non-genetic intervention known to date to slow the onset of ... more Caloric restriction (CR) is the only non-genetic intervention known to date to slow the onset of age-related diseases and increase average and maximum lifespan in several species. Its interest is continually growing, particularly for the identification of mechanisms involved in increasing longevity. Unlike studies in invertebrate and rodent models have provided some indication about the mechanisms of the CR, the efficacy of CR as an anti-aging protocol in primates has not yet been fully established. In this review we present the advantages of using non human primates as relevant models to the study of human aging in general and specifically in the context of therapeutic interventions applicable to humans, such as CR. Through the longitudinal findings in the Grey Mouse Lemur (Microcebus murinus), we stress the importance of primate studies in the context of research on aging and their potential to advance the development of molecules which can mimic the beneficial effects of CR, alre...
All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural p... more All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural parameters. These biological rhythms are endogenously generated by a circadian clock, and they are entrained by cyclic variations of environmental factors called synchronizers. Aging is associated with changes in amplitude and temporal organization of many daily and seasonal rhythms. In humans, daily rhythms of sleep, thermoregulation and hormonal secretion are severely altered with aging. Except in humans, studies on primates are scarce. However, age-related effects on biological rhythms are relatively consistent among primate species studied to date, including humans. Therefore, non human primates are of valuable use for such investigations. Most studies have been performed on the Rhesus macaque (longevity 35-40 years) and on the gray mouse lemur (longevity 10-12 years). Like in humans, the rest-activity rhythm becomes fragmented in aged primates, and shows an increased activity during ...
SUMMARY As ecosystems undergo changes worldwide, physiological flexibility is likely to be an imp... more SUMMARY As ecosystems undergo changes worldwide, physiological flexibility is likely to be an important adaptive response to increased climate instability. Extreme weather fluctuations impose energetical constraints such as unpredictable food shortage. We tested how grey mouse lemurs (Microcebus murinus) could adjust their daily heterothermy and locomotor activity to these ‘energetic accidents’ with a food restriction experiment. The experimental design consisted of acute calorie restriction (2 weeks, 80% restriction) in the middle of winter, after a fattening season with low (11 weeks, 40% restriction) versus high (ad libitum) food availability. This design aimed at simulating the combined effects of the quality of the fattening season (acclimation effect) and a sudden, severe food shortage during the lean season. Hour of start and duration of torpor were the most flexible components of energy savings, increasing in response to the acute food shortage with facilitation by chronic r...
ABSTRACT Introduction Les modèles animaux de la maladie d’Alzheimer sont nécessaires à la compréh... more ABSTRACT Introduction Les modèles animaux de la maladie d’Alzheimer sont nécessaires à la compréhension de la physiopathologie et à l’évaluation de traitements potentiels. Les biomarqueurs tels que le peptide Aβ retrouvé dans le plasma de modèles animaux peuvent permettre d’évaluer l’efficacité de ces traitements ainsi que de suivre l’évolution de la pathologie chez des modèles spontanés ou induits. Le but de notre étude était de développer l’utilisation de l’Aβ plasmatique comme biomarqueur chez des souris transgéniques modèles d’amyloïdose et chez un modèle de vieillissement spontané, le primate microcèbe murin. Matériel et méthodes La concentration du peptide Aβ a été évaluée chez des souris APPswe/PS1dE9 et chez des microcèbes âgés de 1 à 8 ans (n=27). Les souris, âgées de 16 à 116 semaines, étaient issues de différents fonds génétiques (B6C3F1 (n=20) et C57Bl6 (n=23). Les prélèvements sanguins ont été effectués sur des tubes EDTA, centrifugés (2000g ; 10min, 4°c). Le surnageant a été collecté dans des tubes en polypropylène. Un cocktail d’inhibiteurs de protéases (Complete Mini Roche) a été ajouté aux échantillons de plasma. La détection de l’Aβ40 et 42 a été effectuée avec des kits ELISA commerciaux (BioSource). Résultats Nous avons observé une différence significative entre les taux d’Aβ plasmatique chez des souris APPswe/ PS1dE9 de différents fonds génétiques. Par exemple, les taux d’Aβ40 étaient respectivement de 988±75 et 591±37 pg/ml chez les souris B6C3F1 et C57BL/6J. Cependant, les taux d’Aβ40 et 42 plasmatiques chez les souris n’étaient pas modifiés avec l’âge ou l’évolution de la pathologie. Chez le microcèbe, aucune différence significative des taux d’Aβ40 n’a pu être observée entre les animaux jeunes et âgés (41.7±2.4 et 52.3±7.5 pg/ml). Cependant, une plus grande hétérogénéité était présente chez les microcèbes âgés, ceci pouvant être un indicateur d’un vieillissement pathologique de type Alzheimer chez certains animaux. Conclusion La détection des taux d’Aβ plasmatique est un outil simple et très précis chez la souris transgénique et le primate. Cet outil peut permettre de suivre les effets de traitements. Il pourra également permettre de sélectionner des animaux pour l’étude du vieillissement pathologique chez le microcèbe. Remerciements Association France-Alzheimer, National Institute on Aging (R01-AG020197).
Proceedings of the Royal Society B: Biological Sciences, 2011
Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to un... more Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to understand the evolution of polyandry have often focused on its adaptive value to females, whereas ‘convenience polyandry’ might simply decrease the costs of sexual harassment. We tested whether constraint-free female strategies favour promiscuity over mating selectivity through an original experimental design. We investigated variation in mating behaviour in response to a reversible alteration of sexual dimorphism in body mass in the grey mouse lemur, a small primate where female brief sexual receptivity allows quantifying polyandry. We manipulated body condition in captive females, predicting that convenience polyandry would increase when females are weaker than males, thus less likely to resist their solicitations. Our results rather support the alternative hypothesis of ‘adaptive polyandry’: females in better condition are more polyandrous. Furthermore, we reveal that multiple mating i...
A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learni... more A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD) impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus), which is an interesting model of aging and Alzheimer's disease (AD). Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.
Among anthropogenic pressures, light pollution altering light/dark cycles and changing the noctur... more Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14 th night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes.
öIn mammals, a number of anatomical and functional changes occur in the circadian timing system w... more öIn mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modi¢ed by various factors which induce a number of pathological changes. In a small primate, the gray mouse lemur (Microcebus murinus), long-term acceleration of seasonal rhythms by exposing the animals to a shortened photoperiodic regime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model for challenging the idea that modi¢cations of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the e¡ect of aging and accelerated aging on the circadian pacemaker of this primate, we measured body weight variations, the daily rhythm in urine 6-sulfatoxymelatonin and the light-induced expression of the immediate early gene (Fos) in the suprachiasmatic nucleus of mouse lemurs that had been exposed to di¡erent photoperiodic cycles. Urine samples were collected throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nucleus was studied by exposing the animals to a 15-min monochromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (10 11 or 10 14 photons/cm 2 /s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was signi¢cantly altered in aged mouse lemurs which failed to show a nocturnal peak. Fos expression following exposure to low levels of irradiance was reduced by 88% in the suprachiasmatic nucleus of aged mouse lemurs. Exposure to higher irradiance levels showed similar results, with a reduction of 66% in Fos expression in the aged animals. Animals subjected to arti¢cially accelerated aging demonstrated the same alterations in melatonin production and Fos response to light as animals that had been maintained in a routine photoperiodic cycle. Our data indicate that there are dramatic changes in melatonin production and in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of expressed seasonal cycles rather than on a ¢xed chronological age. These results provide new insights into the mechanisms underlying arti¢cial accelerated aging at the level of the molecular mechanisms of the biological clock.
Torpor is an energy-saving mechanism that allows endotherms to overcome energetic challenges. Tor... more Torpor is an energy-saving mechanism that allows endotherms to overcome energetic challenges. Torpor should be avoided during reproduction because of potential incompatibility with offspring growth. To test if torpor can be used during gestation and lactation to compensate for food shortage, we exposed reproductive female grey mouse lemurs (Microcebus murinus), a heterothermic primate, to different levels of food availability. Torpor use was characterised by daily skin temperature profiles, and its energetic outcome was assessed from changes in body mass. Food shortage triggered torpor during the end of the gestation period (n01), ranging from shallow in response to 40% food restriction to deep daily torpor in response to 80% restriction. During the early period of lactation, females fed ad libitum (n02) or exposed to a 40% restriction (n04) remained normothermic; but 80% food restricted females (n05) gave priority to energy saving, increasing the frequency and depth of torpor bouts. The use of torpor was insufficient to compensate for 80% energetic shortage during lactation resulting in loss of mass from the mother and delayed growth in the pups. This study provides the first evidence that a heterothermic primate can use torpor to compensate for food shortages even during reproduction. This physiological flexibility likely evolved as a response to climate-driven fluctuations in food availability in Madagascar.
Background Hematologic and biochemical data are needed to characterize the health status of anima... more Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus). Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years), middle-aged (4–5 years) and old (6–10 years). Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction), the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, w...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
Huddling is considered as a social strategy to reduce thermal stress and promote growth in newbor... more Huddling is considered as a social strategy to reduce thermal stress and promote growth in newborn altricial mammals. So far, the role of huddling on the allocation of saved energy has not been quantified nor have the related impacts on body temperature rhythms. To determine the energy partitioning of rabbit pups either raised alone or in groups of eight, four, or two individuals, when thermoregulatory inefficient (TI) and efficient (TE), we first investigated their total energy expenditure and body composition. We then monitored body temperature and activity rhythms to test whether huddling may impact these rhythms, centered on the suckling event. Pups in a group of eight utilized 40% less energy for thermogenesis when TI than did pups alone and 32% less energy when TE. Pups in groups of eight and four had significantly lower thermoregulatory costs in the TI period, whereas pups in groups of two, four, and eight had lower costs during the TE period. Huddling pups could therefore ch...
The cost of reproduction (CoR) is a central mechanism in the evolution of species' life-history t... more The cost of reproduction (CoR) is a central mechanism in the evolution of species' life-history traits. Because acquired resources are finite, fitness is maximized for an optimal balance between the allocation to current fecundity versus the allocation to survival and future reproduction (Cody, 1966; Reznick, 1985; Stearns, 1989; Williams, 1966). This has proved a robust theory for explaining the difference in life-history strategies within and between clades (e.g.,Charnov, 2002; Linden & Møller, 1989). Within species however, the role played by CoR in generating variance in individuals' life trajectories is yet largely unknown. Experimental procedures-such as artificially increasing reproductive load-generally succeed to evidence costs (see in Boonekamp, Salomons, Bouwhuis, Dijkstra, & Verhulst, 2014; reviewed in Santos & Nakagawa, 2012). But evidencing CoR from longitudinal demographic data has proved difficult. It is particularly the case for evidencing survival CoR (rather than reproductive CoR as in Kroeger, Blumstein, Armitage, Reid, & Martin, 2018) and long-term CoR (rather than short-term CoR as in Froy,
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001
To study the temporal organization of daily hypothermia and torpor in a nocturnal Malagasy primat... more To study the temporal organization of daily hypothermia and torpor in a nocturnal Malagasy primate, the gray mouse lemur, body temperature (Tb) and locomotor activity were recorded using telemetry on 39 males held in 24-h light-dark cycles of different photoperiods. Under free-running condition, the circadian Tb and locomotor activity rhythms had a period shorter than 24 h. Circadian daily hypothermia started by a rapid drop in Tb (0.24°C/10 min) at the end of subjective night (13 h 25 ± 20 min) and was characterized by minimal Tb values 3 h 20 ± 5 min later. Spontaneous arousal from daily hypothermia occurred at a fixed time (6 h 05 ± 15 min, n = 7) after the beginning of subjective day. In animals exposed to 24-h light-dark cycles with night duration varying from 10 to 14 h, locomotor activity was strictly restricted to dark time, but the temporal organization of daily hypothermia was not modified, although changes in amplitude of Tb rhythm were observed. Daily hypothermia was dir...
Ageing results from the accumulation of multifactorial damage over time. However, the temporal di... more Ageing results from the accumulation of multifactorial damage over time. However, the temporal distribution of this damage remains unknown. In seasonal species, transitions between seasons are critical periods of massive physiological remodelling. We hypothesised that these recurrent peaks of physiological remodelling are costly in terms of survival. We tested whether captive small primates exposed to an experimentally increased frequency of seasonal transitions die sooner than individuals living under natural seasonality. The results show that experiencing one additional season per year increases the mortality hazard by a factor of 3 to 4, whereas the expected number of seasons lived is only slightly impacted by the seasonal rhythm. These results demonstrate that physiological transitions between periods of high and low metabolic activity represent a major mortality risk for seasonal organisms, which has been ignored until now.
INTRODUCTION With the progressive aging of the World population, an increasing number of people s... more INTRODUCTION With the progressive aging of the World population, an increasing number of people suffer from cognitive impairment and dementia. These deficits affect quality of life and cause social, economic and public health problems [1-3]. A clear relationship has been established between age-associated cognitive decline and selective regional brain atrophy from normal aging to dementia [4-5]. Cognitive decline is not homogeneous in humans and the determinants leading to differences between subjects are not fully understood. Middle-aged metabolic disorders [6-8] culminating in type 2 diabetes (T2D) [9-11] could be a risk factor to memory impairment and cerebral atrophy. T2D is characterized by hyperglycaemia (> 7mmol/L), impairment of glucose tolerance leading to insulin resistance [12]. Patients with type 2 diabetes display memory impairment [9-11] and anatomic brain alterations including hippocampus www.aging-us.com
Mammals use variations in the length of day to anticipate environmental changes and time their re... more Mammals use variations in the length of day to anticipate environmental changes and time their reproduction. Light pollution, which affects day length perception, could lead to changes in biological functions. To explore the effects of light pollution on seasonal reproduction, we conducted an experimental study on a strict long-day breeder, the nocturnal gray mouse lemur (Microcebus murinus). Twelve females were randomly exposed to either a moonlight treatment or a light pollution treatment for 5 weeks during the transition from a short-to long-day photoperiod. Daily rhythms of locomotor activity and core temperature were recorded, and the occurrence of estrus and urinary 17-β-estradiol concentrations were monitored. In females exposed to light pollution, the first seasonal estrus occurred while they were still in a short-day photoperiod, 2 weeks earlier than in females exposed to moonlight. Moreover, the daily rhythms profiles of females exposed to light pollution showed significant changes that mimicked long-day acclimatization. This study demonstrates that light pollution can affect daily rhythms and the timing of seasonal estrus in a primate and suggests that functional changes in the circadian system may underlie the adverse effects of light pollution that are observed in wildlife.
-Au cours du vieillissement, la capacité des organismesà s'adapterà leur environnement est altéré... more -Au cours du vieillissement, la capacité des organismesà s'adapterà leur environnement est altérée. Chez l'Homme, les troubles liésà l'âge incluent l'apparition de perturbations des rythmes biologiques, notamment des rythmes veille/sommeil, des rythmes de température corporelle et de sécrétion d'hormones. L'altération des rythmes biologiques avec l'âge peut avoir des conséquences majeures sur la santé, notamment du fait de l'altération des rythmes veille-sommeil qui entraîne une forte altération de l'état général des individus. L'étude de ces altérations constitue de ce fait un enjeu de santé majeur et nécessite l'utilisation de modèles animaux appropriés, tels que le microcèbe (Microcebus murinus), un petit primate malgache aux rythmes biologiques très prononcés.
Caloric restriction (CR) is the only non-genetic intervention known to date to slow the onset of ... more Caloric restriction (CR) is the only non-genetic intervention known to date to slow the onset of age-related diseases and increase average and maximum lifespan in several species. Its interest is continually growing, particularly for the identification of mechanisms involved in increasing longevity. Unlike studies in invertebrate and rodent models have provided some indication about the mechanisms of the CR, the efficacy of CR as an anti-aging protocol in primates has not yet been fully established. In this review we present the advantages of using non human primates as relevant models to the study of human aging in general and specifically in the context of therapeutic interventions applicable to humans, such as CR. Through the longitudinal findings in the Grey Mouse Lemur (Microcebus murinus), we stress the importance of primate studies in the context of research on aging and their potential to advance the development of molecules which can mimic the beneficial effects of CR, alre...
All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural p... more All living organisms exhibit rhythmic activities in a wide variety of endocrine and behavioural parameters. These biological rhythms are endogenously generated by a circadian clock, and they are entrained by cyclic variations of environmental factors called synchronizers. Aging is associated with changes in amplitude and temporal organization of many daily and seasonal rhythms. In humans, daily rhythms of sleep, thermoregulation and hormonal secretion are severely altered with aging. Except in humans, studies on primates are scarce. However, age-related effects on biological rhythms are relatively consistent among primate species studied to date, including humans. Therefore, non human primates are of valuable use for such investigations. Most studies have been performed on the Rhesus macaque (longevity 35-40 years) and on the gray mouse lemur (longevity 10-12 years). Like in humans, the rest-activity rhythm becomes fragmented in aged primates, and shows an increased activity during ...
SUMMARY As ecosystems undergo changes worldwide, physiological flexibility is likely to be an imp... more SUMMARY As ecosystems undergo changes worldwide, physiological flexibility is likely to be an important adaptive response to increased climate instability. Extreme weather fluctuations impose energetical constraints such as unpredictable food shortage. We tested how grey mouse lemurs (Microcebus murinus) could adjust their daily heterothermy and locomotor activity to these ‘energetic accidents’ with a food restriction experiment. The experimental design consisted of acute calorie restriction (2 weeks, 80% restriction) in the middle of winter, after a fattening season with low (11 weeks, 40% restriction) versus high (ad libitum) food availability. This design aimed at simulating the combined effects of the quality of the fattening season (acclimation effect) and a sudden, severe food shortage during the lean season. Hour of start and duration of torpor were the most flexible components of energy savings, increasing in response to the acute food shortage with facilitation by chronic r...
ABSTRACT Introduction Les modèles animaux de la maladie d’Alzheimer sont nécessaires à la compréh... more ABSTRACT Introduction Les modèles animaux de la maladie d’Alzheimer sont nécessaires à la compréhension de la physiopathologie et à l’évaluation de traitements potentiels. Les biomarqueurs tels que le peptide Aβ retrouvé dans le plasma de modèles animaux peuvent permettre d’évaluer l’efficacité de ces traitements ainsi que de suivre l’évolution de la pathologie chez des modèles spontanés ou induits. Le but de notre étude était de développer l’utilisation de l’Aβ plasmatique comme biomarqueur chez des souris transgéniques modèles d’amyloïdose et chez un modèle de vieillissement spontané, le primate microcèbe murin. Matériel et méthodes La concentration du peptide Aβ a été évaluée chez des souris APPswe/PS1dE9 et chez des microcèbes âgés de 1 à 8 ans (n=27). Les souris, âgées de 16 à 116 semaines, étaient issues de différents fonds génétiques (B6C3F1 (n=20) et C57Bl6 (n=23). Les prélèvements sanguins ont été effectués sur des tubes EDTA, centrifugés (2000g ; 10min, 4°c). Le surnageant a été collecté dans des tubes en polypropylène. Un cocktail d’inhibiteurs de protéases (Complete Mini Roche) a été ajouté aux échantillons de plasma. La détection de l’Aβ40 et 42 a été effectuée avec des kits ELISA commerciaux (BioSource). Résultats Nous avons observé une différence significative entre les taux d’Aβ plasmatique chez des souris APPswe/ PS1dE9 de différents fonds génétiques. Par exemple, les taux d’Aβ40 étaient respectivement de 988±75 et 591±37 pg/ml chez les souris B6C3F1 et C57BL/6J. Cependant, les taux d’Aβ40 et 42 plasmatiques chez les souris n’étaient pas modifiés avec l’âge ou l’évolution de la pathologie. Chez le microcèbe, aucune différence significative des taux d’Aβ40 n’a pu être observée entre les animaux jeunes et âgés (41.7±2.4 et 52.3±7.5 pg/ml). Cependant, une plus grande hétérogénéité était présente chez les microcèbes âgés, ceci pouvant être un indicateur d’un vieillissement pathologique de type Alzheimer chez certains animaux. Conclusion La détection des taux d’Aβ plasmatique est un outil simple et très précis chez la souris transgénique et le primate. Cet outil peut permettre de suivre les effets de traitements. Il pourra également permettre de sélectionner des animaux pour l’étude du vieillissement pathologique chez le microcèbe. Remerciements Association France-Alzheimer, National Institute on Aging (R01-AG020197).
Proceedings of the Royal Society B: Biological Sciences, 2011
Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to un... more Classic sex roles depict females as choosy, but polyandry is widespread. Empirical attempts to understand the evolution of polyandry have often focused on its adaptive value to females, whereas ‘convenience polyandry’ might simply decrease the costs of sexual harassment. We tested whether constraint-free female strategies favour promiscuity over mating selectivity through an original experimental design. We investigated variation in mating behaviour in response to a reversible alteration of sexual dimorphism in body mass in the grey mouse lemur, a small primate where female brief sexual receptivity allows quantifying polyandry. We manipulated body condition in captive females, predicting that convenience polyandry would increase when females are weaker than males, thus less likely to resist their solicitations. Our results rather support the alternative hypothesis of ‘adaptive polyandry’: females in better condition are more polyandrous. Furthermore, we reveal that multiple mating i...
A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learni... more A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD) impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus), which is an interesting model of aging and Alzheimer's disease (AD). Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.
Among anthropogenic pressures, light pollution altering light/dark cycles and changing the noctur... more Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14 th night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes.
öIn mammals, a number of anatomical and functional changes occur in the circadian timing system w... more öIn mammals, a number of anatomical and functional changes occur in the circadian timing system with aging. In certain species, aging can be modi¢ed by various factors which induce a number of pathological changes. In a small primate, the gray mouse lemur (Microcebus murinus), long-term acceleration of seasonal rhythms by exposing the animals to a shortened photoperiodic regime (up to 2.5 times the natural photoperiodic regime) alters longevity, based on survival curves and morphological changes. This provides a model for challenging the idea that modi¢cations of the circadian pacemaker are related to chronological (years) versus biological (photoperiodic cycles) age. To assess the e¡ect of aging and accelerated aging on the circadian pacemaker of this primate, we measured body weight variations, the daily rhythm in urine 6-sulfatoxymelatonin and the light-induced expression of the immediate early gene (Fos) in the suprachiasmatic nucleus of mouse lemurs that had been exposed to di¡erent photoperiodic cycles. Urine samples were collected throughout the day and urine 6-sulfatoxymelatonin levels were measured by radioimmunoassay. Light-induced Fos expression in the suprachiasmatic nucleus was studied by exposing the animals to a 15-min monochromatic pulse of light (500 nm) at saturating or sub-saturating levels of irradiance (10 11 or 10 14 photons/cm 2 /s) during the dark phase. The classical pattern of 6-sulfatoxymelatonin excretion was signi¢cantly altered in aged mouse lemurs which failed to show a nocturnal peak. Fos expression following exposure to low levels of irradiance was reduced by 88% in the suprachiasmatic nucleus of aged mouse lemurs. Exposure to higher irradiance levels showed similar results, with a reduction of 66% in Fos expression in the aged animals. Animals subjected to arti¢cially accelerated aging demonstrated the same alterations in melatonin production and Fos response to light as animals that had been maintained in a routine photoperiodic cycle. Our data indicate that there are dramatic changes in melatonin production and in the cellular response to photic input in the suprachiasmatic nucleus of aged mouse lemurs, and that these alterations depend on the number of expressed seasonal cycles rather than on a ¢xed chronological age. These results provide new insights into the mechanisms underlying arti¢cial accelerated aging at the level of the molecular mechanisms of the biological clock.
Torpor is an energy-saving mechanism that allows endotherms to overcome energetic challenges. Tor... more Torpor is an energy-saving mechanism that allows endotherms to overcome energetic challenges. Torpor should be avoided during reproduction because of potential incompatibility with offspring growth. To test if torpor can be used during gestation and lactation to compensate for food shortage, we exposed reproductive female grey mouse lemurs (Microcebus murinus), a heterothermic primate, to different levels of food availability. Torpor use was characterised by daily skin temperature profiles, and its energetic outcome was assessed from changes in body mass. Food shortage triggered torpor during the end of the gestation period (n01), ranging from shallow in response to 40% food restriction to deep daily torpor in response to 80% restriction. During the early period of lactation, females fed ad libitum (n02) or exposed to a 40% restriction (n04) remained normothermic; but 80% food restricted females (n05) gave priority to energy saving, increasing the frequency and depth of torpor bouts. The use of torpor was insufficient to compensate for 80% energetic shortage during lactation resulting in loss of mass from the mother and delayed growth in the pups. This study provides the first evidence that a heterothermic primate can use torpor to compensate for food shortages even during reproduction. This physiological flexibility likely evolved as a response to climate-driven fluctuations in food availability in Madagascar.
Background Hematologic and biochemical data are needed to characterize the health status of anima... more Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus). Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years), middle-aged (4–5 years) and old (6–10 years). Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction), the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, w...
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
Huddling is considered as a social strategy to reduce thermal stress and promote growth in newbor... more Huddling is considered as a social strategy to reduce thermal stress and promote growth in newborn altricial mammals. So far, the role of huddling on the allocation of saved energy has not been quantified nor have the related impacts on body temperature rhythms. To determine the energy partitioning of rabbit pups either raised alone or in groups of eight, four, or two individuals, when thermoregulatory inefficient (TI) and efficient (TE), we first investigated their total energy expenditure and body composition. We then monitored body temperature and activity rhythms to test whether huddling may impact these rhythms, centered on the suckling event. Pups in a group of eight utilized 40% less energy for thermogenesis when TI than did pups alone and 32% less energy when TE. Pups in groups of eight and four had significantly lower thermoregulatory costs in the TI period, whereas pups in groups of two, four, and eight had lower costs during the TE period. Huddling pups could therefore ch...
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