Search

Maximal lifespan of mammalian species, even if closely related, may differ more than 10-fold, however the nature of the mechanisms that determine this variability is unresolved. Here, we assess the relationship between maximal lifespan duration and concentrations of more than 20,000 lipid compounds, measured in 669 tissue samples from 6 tissues of 35 species representing three mammalian clades: primates, rodents and bats. We identify lipids associated with species' longevity across the three clades, uncoupled from other parameters, such as basal metabolic rate, body size, or body temperature. These lipids clustered in specific lipid classes and pathways, and enzymes linked to them display signatures of greater stabilizing selection in long-living species, and cluster in functional groups related to signaling and protein-modification processes. These findings point towards the existence of defined molecular mechanisms underlying variation in maximal lifespan among mammals.

Maximal lifespan of mammalian species, even if closely related, may differ more than 10-fold, however the nature of the mechanisms that determine this variability is unresolved. Here, we assess the relationship between maximal lifespan duration and concentrations of more than 20,000 lipid compounds, measured in 669 tissue samples from 6 tissues of 35 species representing three mammalian clades: primates, rodents and bats. We identify lipids associated with species’ longevity across the three clades, uncoupled from other parameters, such as basal metabolic rate, body size, or body temperature. These lipids clustered in specific lipid classes and pathways, and enzymes linked to them display signatures of greater stabilizing selection in long-living species, and cluster in functional groups related to signaling and protein-modification processes. These findings point towards the existence of defined molecular mechanisms underlying variation in maximal lifespan among mammals.

Bilateral multifocal corneal opacity was detected in a 4.5-year-old male captive gray mouse lemur (Microcebus murinus) without other clinical ocular changes. Histopathological examination revealed a severe diffuse granulomatous scleritis and focal keratitis with intralesional cholesterol, consistent with xanthomatous inflammation. This is the first report of xanthomatous inflammation in a gray mouse lemur. This condition may be the result of systemic factors (lipid metabolism disorders) and/or local predisposing factors such as hemorrhage or inflammation. The pathogenesis in this case could not be fully determined. Further studies on lemurs are required for a better understanding of their lipid metabolism, as well as for diagnosing and evaluating the incidence of xanthomatous inflammation in these species.

Through its antioxidant, anticarcinogenic, and anti-inflammatory properties, resveratrol has become a candidate for drug development in the context of aging studies. Scientific evidence has highlighted its potential as a therapeutic agent for cardiovascular diseases and some cancers but also as an antiaging molecule. Resveratrol is thought to mimic the beneficial effects of chronic and moderate calorie restriction. Nevertheless, no study has demonstrated the prolongation of life span in healthy nonobese mammal models. This review summarizes recent findings on the effects of resveratrol on aging and life span in mammals. In our opinion, more studies should be performed to assess the effects of a chronic dietary intake of resveratrol in long-lived species close to humans, such as nonhuman primates. This will certainly generate more evidence about the ability of resveratrol to achieve the physiological benefits that have been observed in small mammal laboratory models and feature the eventual unwanted secondary effects that may occur under high levels of resveratrol.

Ageing is known to induce profound effects on physiological functions but only a few studies have focused on its behavioural alterations. Orb-webs of spiders, however, provide an easily analysable structure, the result of complex sequences of stereotypical behaviours that are particularly relevant to the study of ageing processes. We chose the orb spider Zygiella x-notata as an invertebrate organism to investigate alterations in web geometry caused by ageing. Parameters taken into account to compare webs built by spiders at different ages were: the length of the capture spiral (CTL), the number of anomalies per cm, and four parameters of web regularity (the angle between radii, the number of spiral thread units connecting two successive radii, the parallelism and the coefficient of variation of the distances between silk threads of two adjacent spiral turns). All web parameters were related to ageing. Two groups of spiders emerged: short- and long-lived spiders (with a higher body mass), with an average life span of 150 and 236 days, respectively. In both short- and long-lived spiders' webs, the CTL and the silk thread parallelism decreased, while the variation of the distances between silk threads increased. However, the number of anomalies per cm and the angle between radii increased in short-lived spiders only. These modifications can be explained by ageing alterations in silk investment and cognitive and/or locomotor functions. Orb-web spiders would therefore provide a unique invertebrate model to study ageing and its processes in the alterations of behavioural and cognitive functions.

The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg−1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.

International audience; Background: Very few studies have investigated the influence of regular practice of a stereotyped behaviour on its future expression. In spiders, orb-web construction is a succession of repetitive and stereotyped behaviours and is a relevant model for such study. This study examined if preventing spiders from building influences their future constructions. Spiders were caught in the field and brought back to the laboratory where they were exposed to two different situations; half were maintained in small boxes where web building was not possible, and half were maintained in large enclosures where they could build orb-webs. All spiders were tested twice: 1 week after their capture (test 1) and 12 weeks later (test 2). Their building performance was evaluated by examining silk investment (length of the capture spiral, number of radii, of spiral turns, length of the lower part of the web), web design (mesh height, asymmetry) and the frequency of anomalies in the web. Results: There was no difference in web constructions between the two groups in either test. However, the rearing conditions seemed to affect two parameters: the length of the lower part of the web and the asymmetry were higher for spiders reared in small boxes. We did find also, an overall decrease with time in silk investment (length of the capture spiral, capture area) in both groups as well as an increase in the number of anomalies of the capture spiral from tests 1 to 2. Conclusions: These results suggest that regular web construction does not have a strong effect on web structure or silk investment, but spider age did affect parameters in the two groups. Thus, the lack of practice over a large portion of a spider's adult life does not affect a stereotyped behaviour such as the building of an orb-web.

Through its antioxidant, anticarcinogenic, and anti-inflammatory properties, resveratrol has become a candidate for drug development in the context of aging studies. Scientific evidence has highlighted its potential as a therapeutic agent for cardiovascular diseases and some cancers but also as an antiaging molecule. Resveratrol is thought to mimic the beneficial effects of chronic and moderate calorie restriction. Nevertheless, no study has demonstrated the prolongation of life span in healthy nonobese mammal models. This review summarizes recent findings on the effects of resveratrol on aging and life span in mammals. In our opinion, more studies should be performed to assess the effects of a chronic dietary intake of resveratrol in long-lived species close to humans, such as nonhuman primates. This will certainly generate more evidence about the ability of resveratrol to achieve the physiological benefits that have been observed in small mammal laboratory models and feature the eventual unwanted secondary effects that may occur under high levels of resveratrol.

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, already observed in some species, without imposing a reduced calorie diet.

International audience; Among animal constructions, the orb webs of spiders are perfect geometrical architectural models. Webs are constructed by means of a succession of behaviours, which are often considered as instinctive and stereotyped. Anomalies in web structure are considered to be a consequence of variability in behaviour. In order to assess the variability in web structure, the spider Zygiella x-notata was allowed to build webs in the laboratory under standardized conditions. Webs (n = 127) were examined for anomalies, which were defined as modifications in the geometrical structure. Ten anomalies in the structure of webs produced by females, aged from 16 to 21 days after their adult moult, are described. The frequency of anomalies per web varies from 5 to 98. A very low percentage of the spiral elements of a web (less than 5%) were affected. Anomalies in the radii were less numerous (mean = 3 +/- 3) than those in the sticky spiral (mean = 21 +/- 11). Anomalies in the sticky spiral were different and more frequent in the peripheral than central parts of the webs. They were also relatively more numerous in the upper than in the lower part of the webs. Total number of anomalies was positively correlated with particular web characteristics (capture area, length of capture thread, width of the lower part of the web and mean distance between two spiral turns in the lower part) but not to the physical characteristics of the spiders (mass and size). Our results indicate that the orb webs of spiders, which are considered to be perfect geometrical structures, include anomalies mainly in the structure of the sticky spiral. These anomalies were the result of variability in behaviour during web building. In conclusion, their identification and description enable one to use them in spider webs as an index of behavioural variability.

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, already observed in some species, without imposing a reduced calorie diet.

International audience; The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg*day(-1)*kg(-1)). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes.

International audience; A life-long follow-up of physiological and behavioural functions was initiated in 38-month-old mouse lemurs (Microcebus murinus) to test whether caloric restriction (CR) or a potential mimetic compound, resveratrol (RSV), can delay the ageing process and the onset of age-related diseases. Based on their potential survival of 12 years, mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake and a RSV group (200 mg/kg.day(-1)) fed ad libitum. Since this prosimian primate exhibits a marked annual rhythm in body mass gain during winter, animals were tested throughout the year to assess body composition, daily energy expenditure (DEE), resting metabolic rate (RMR), physical activity and hormonal levels. After 1 year, all mouse lemurs seemed in good health. CR animals showed a significantly decreased body mass compared with the other groups during long day period only. CR or RSV treatments did not affect body composition. CR induced a decrease in DEE without changes in RMR, whereas RSV induced a concomitant increase in DEE and RMR without any obvious modification of locomotor activity in both groups. Hormonal levels remained similar in each group. In summary, after 1 year of treatment CR and RSV induced differential metabolic responses but animals successfully acclimated to their imposed diets. The RESTRIKAL study can now be safely undertaken on a long-term basis to determine whether age-associated alterations in mouse lemurs are delayed with CR and if RSV can mimic these effects.

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, which was higher among females. Additionally, blood urea nitrogen significantly increased with age and is potentially linked to chronic renal insufficiency, which has been described in captive mouse lemurs. The results demonstrated significant effects related to season, especially in blood protein levels and glucose rates; these effects were observed regardless of gender or age and were likely due to seasonal variations in food intake, which is very marked in this species. Conclusion These results were highly similar with those obtained in other primate species and can serve as references for future research of the Grey Mouse Lemur.