Resveratrol dietary supplementation shortens the free-running circadian period and decreases body temperature in a prosimian primate

Resveratrol (RSV) is a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. We tested the effect of RSV on the circadian clock in a nonhuman primate, the gray mouse lemur. The impact of a 2-week dietary supplementation of RSV on the rhythms of locomotor activity and body temperature in constant dark conditions (DD) was investigated in young (n = 7) and old (n = 6) animals. RSV supplementation followed 2 weeks in DD under normal diet (CTL). In both young and old animals receiving RSV, we observed a shortening of the free-running period compared to those under CTL (-15 minutes in young animals and -45 minutes in old animals), accompanied by a lower mean body temperature in both age groups and decreased locomotor activity in young animals. Thus, RSV is a food component capable of influencing a primate's circadian clock. This property may be of interest clinically in the context of the treatment of circadian disruption and in the context of the effects of RSV ingestion on health.     

Effects of chronic calorie restriction or dietary resveratrol supplementation on insulin sensitivity markers in a primate, Microcebus murinus

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.     

Detection and Identification by PCR of a Highly Virulent Phylogenetic Subgroup among Extraintestinal Pathogenic Escherichia coli B2 Strains

Closely related Escherichia coli B2 strains O1:K1, O2:K1, O18:K1, and O45:K1 constitute a major subgroup causing extraintestinal infections. A DNA pathoarray analysis was used to develop a PCR specific for this subgroup that was included in the multiplex phylogenetic-grouping PCR method. Our PCR may serve to identify this virulent subgroup among different ecological niches.     

Effects of dietary resveratrol on the sleep-wake cycle in the non-human primate gray mouse lemur (Microcebus murinus)

Converging evidence shows that the non-human primate gray mouse lemur (Microcebus murinus) is ideal for the study of the aging process and for testing the effects of new therapies and dietary interventions on age-associated pathologies. One such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. However, little is known about the effect of RSV on the lemur sleep-wake cycle, which reflects mammalian brain function and health. In the present study, the authors investigated this effect by comparing sleep-wake cycles in adult lemurs based on electroencephalographic (EEG) rhythms. The effect of short-term RSV supplementation on the sleep-wake cycle of mouse lemurs was evaluated in entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of RSV supplementation, the animals exhibited a significantly increased proportion of active-wake time, occurring mainly during the resting phase of the sleep-wake cycle (+163%). The increase in active-wake time with RSV supplementation was accompanied by a significant reduction of both paradoxical sleep (-95%) and slow-wave sleep (-38%). These changes mainly occurred during the resting phase of the sleep-wake cycle (RSV supplementation induced negligible changes in active-wake time during the active phase of the sleep-wake cycle). The present data suggest that RSV may be a potent regulator of sleep-wake rhythms and could be of major interest in the study of sleep perturbations associated with aging and neuropathology.     

A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire.     

Regulation by Photoperiod of Seasonal Changes in Body Mass and Reproductive Function in Gray Mouse Lemurs (Microcebus murinus): Differential Responses by Sex

Microcebus murinus exhibits highly seasonal biological rhythms to cope with extreme seasonality in availability of resources. To study the role of daylength on seasonal changes in body mass and reproductive function, we exposed male and female gray mouse lemurs to natural, constant, or alternating light cycles for 2 years under constant environmental conditions. When exposed to either constant short (SD: 10 h light/day), long (LD: 14 h light/day), or intermediate (ID: 12 h light/day) daylength, males and females maintained a constant body mass with no spontaneous cyclic variation. We only observed typical seasonal body mass changes in subjects exposed to alternating periods of SD and LD, the weight gain being triggered by SD, whereas weight loss occurred under LD. Reproductive activity in females proceeded from an endogenous rhythm that was expressed under constant daylengths. In contrast, changes in reproductive activity in males depended on daylength variation. In both sexes, SD and LD have direct inhibitory or stimulatory effects on reproductive activity. In females, daylength regulates breeding season by synchronizing an endogenous sexual rhythm with the season, whereas in males, the perception of a critical photoperiod is used to determine the subsequent onset or arrest of their breeding season. These sexual differences in the effect of daylength could be related to sex-specific differences in reproductive constraints.     

Effect of Ambient Temperature on the Body Temperature Rhythm of Male Gray Mouse Lemurs (Microcebus murinus)

In order to cope with the seasonal variations in ambient temperature and food availability in the natural habitat, gray mouse lemurs (Microcebus murinus) exhibit adaptive energy-saving mechanisms similar to those in hibernating species with seasonal and daily heterothermia. To determine thermoregulatory responses, via telemetry we recorded body temperature and locomotor activity variations during the breeding season in three captive male mouse lemurs kept at ambient temperatures (T_a) ranging from 18° to 34°C. Rhythms in body temperature and locomotor activity were clearly exhibited regardless of ambient temperature. As _a increased, mean body temperature increased from 36.5 ± 0.1°C to 37.6 ± 0.3°C, with significant change in the amplitude of the body temperature rhythm when _a rose above 28°C. Effects of _a were mostly due to changes in the fall in body temperature occurring daily at the beginning of the light phase when the subjects entered diurnal sleep. The daily decrease in body temperature was not modified by exposure to ambient temperatures from 18°C to 28°C whereas it disappeared under warmer condition. Changes in locomotor activity levels only delayed the occurrence of thermoregulatory modulation. These results strongly suggest that, during the breeding season, the thermoneutral zone of mouse lemurs is close to 28°C and that the diurnal fall in body temperature could be considered as an important adaptive energy-saving mechanism adjusted to ecological constraints.     

Daily Rhythms of Core Temperature and Locomotor Activity Indicate Different Adaptive Strategies to Cold Exposure in Adult and Aged Mouse Lemurs Acclimated to a Summer-Like Photoperiod

Daily variations in core temperature (Tc) within the normothermic range imply thermoregulatory processes that are essential for optimal function and survival. Higher susceptibility towards cold exposure in older animals suggests that these processes are disturbed with age. In the mouse lemur, a long-day breeder, we tested whether aging affected circadian rhythmicity of Tc, locomotor activity (LA), and energy balance under long-day conditions when exposed to cold. Adult (N?=?7) and aged (N?=?5) mouse lemurs acclimated to LD14/10 were exposed to 10–day periods at 25 and 12°C. Tc and LA rhythms were recorded by telemetry, and caloric intake (CI), body mass changes, and plasma IGF-1 were measured. During exposure to 25°C, both adult and aged mouse lemurs exhibited strong daily variations in Tc. Aged animals exhibited lower levels of nocturnal LA and nocturnal and diurnal Tc levels in comparison to adults. Body mass and IGF-1 levels remained unchanged with aging. Under cold exposure, torpor bout occurrence was never observed whatever the age category. Adult and aged mouse lemurs maintained their Tc in the normothermic range and a positive energy balance. All animals exhibited increase in CI and decrease in IGF-1 in response to cold. The decrease in IGF-1 was delayed in aged mouse lemurs compared to adults. Moreover, both adult and aged animals responded to cold exposure by increasing their diurnal LA compared to those under Ta?=?25°C. However, aged animals exhibited a strong decrease in nocturnal LA and Tc, whereas cold effects were only slight in adults. The temporal organization and amplitude of the daily phase of low Tc were particularly well preserved under cold exposure in both age groups. Sexually active mouse lemurs exposed to cold thus seemed to prevent torpor exhibition and temporal disorganization of daily rhythms of Tc, even during aging. However, although energy balance was not impaired with age in mouse lemurs after cold exposure, aging was associated with lower LA and Tc during the night and delayed decrease in IGF-1. This might reflect that adaptive strategies to cold exposure differ with age in mouse lemurs acclimated to a summer-like photoperiod.     

Female mate choice and male–male competition in Tonkean macaques: Who decides?

The theory of sexual selection predicts that females should be discriminatory in the choice of sexual partners. Females can express their choice in two ways. In direct mate choice, they show preferences for certain partners. In indirect mate choice, they select partners by displaying sexually attractive traits, thus eliciting contest competition between males. We focused on a primate species in which females advertise the timing of their ovulation and studied the balance between these two choice strategies. We tested predictions related to three hypotheses about direct and indirect female choice, namely the best‐male, graded‐signal and weak‐selectivity hypotheses. We investigated the sexual and agonistic interactions occurring during oestrous periods in five captive groups of Tonkean macaques (Macaca tonkeana). The results showed that dominant males used mate guarding to monopolise sexual access to parous females that were in the fertile stage of their reproductive cycle, while lower‐ranking males monitored only nulliparous females. The distribution of sexual presentations indicated that females accepted different types of partners, supporting the weak‐selectivity hypothesis regarding direct mate choice. The analysis of behavioural sequences revealed that mate‐guarding males used mild coercive behaviours to prevent females from mating with other males at conception time. The distribution of mounts showed that females mainly mated with dominant males, which leads us to argue that the best‐male hypothesis provides the most parsimonious explanation regarding indirect mate choice in Tonkean macaques. At the individual level, it may be concluded that male competitive strategies prevented females from exercising direct mate choice. At the evolutionary level, however, female sexual advertising and thus indirect choice promoted competition between males. The outcome is that indirect mate choice appears more important than direct mate choice in female Tonkean macaques.