Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening

Chronic dietary restriction (DR) is considered among the most robust life-extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL) feeding and 6- to 10-fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain-specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal.     

Obestatin与GPR39受体的最新研究进展

肥胖抑制素(obestatin)是新近发现的一种与食欲刺激素有关的多肽(ghrelin-associated peptide,GAP),可以结合孤儿G蛋白GPR39受体,抑制摄食、胃肠功能和体重的增加,被认为是食欲刺激激素(ghrelin)的生物学拮抗剂或阴阳活性多肽.但最新研究认为,obestatin不能与GPR39受体特异性结合,也不能改变ghrelin所诱导的生物学效应.鉴于上述不同的研究报道,就其相关研究成果作一概述.     

When it is costly to have a caring mother: food limitation erases the benefits of parental care in earwigs

The aggregation of parents with offspring is generally associated with different forms of care that improve offspring survival at potential costs to parents. Under poor environments, the limited amount of resources available can increase the level of competition among family members and consequently lead to adaptive changes in parental investment. However, it remains unclear as to what extent such changes modify offspring fitness, particularly when offspring can survive without parents such as in the European earwig, Forficula auricularia. Here, we show that under food restriction, earwig maternal presence decreased offspring survival until adulthood by 43 per cent. This effect was independent of sibling competition and was expressed after separation from the female, indicating lasting detrimental effects. The reduced benefits of maternal presence on offspring survival were not associated with higher investment in future reproduction, suggesting a condition-dependent effect of food restriction on mothers and local mother-offspring competition for food. Overall, these findings demonstrate for the first time a long-term negative effect of maternal presence on offspring survival in a species with maternal care, and highlight the importance of food availability in the early evolution of family life.     

Ghrelin的合成与分泌及其影响因素

Ghrelin是由28个氨基酸组成的一种脑肠肽.除了可以刺激生长激素释放以外,ghrelin具有促进摄食、调节能量代谢等多种中枢及外周的重要功能.本文总结近年关于ghrelin合成与分泌的研究成果,简要介绍ghrelin基因转录、ghrelin蛋白质的加工修饰及其相关调控机制,并从营养物质、激素、自主神经系统、机体生理状态和病理状态等方面,介绍影响ghrelin水平的一些主要因素.     

Characteristics of Food-Entrained Orcadian Rhythms in Rats During Long-Term Exposure to Constant Light

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.     

Characteristics of Food-Entrained Orcadian Rhythms in Rats During Long-Term Exposure to Constant Light

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.     

A general model for ontogenetic growth under food restriction

Food restriction (FR) retards animals' growth. Understanding the underlying mechanisms of this phenomenon is important to conceptual problems in life-history theory, as well as to applied problems in animal husbandry and biomedicine. Despite a considerable amount of empirical data published since the 1930s, there is no relevant general theoretical framework that predicts how animals vary their energy budgets and life-history traits under FR. In this paper, we develop such a general quantitative model based on fundamental principles of metabolic energy allocation during ontogeny. This model predicts growth curves under varying conditions of FR, such as the compensatory growth, different age at which FR begins, its degree and its duration. Our model gives a quantitative explanation for the counterintuitive phenomenon that under FR, lower body temperature and lower metabolism lead to faster growth and larger adult size. This model also predicts that the animals experiencing FR reach the same fraction of their adult mass at the same age as their ad libitum counterparts. All predictions are well supported by empirical data from mammals and birds of varying body size, under different conditions of FR.     

Effects of chronic caloric restriction on mitochondrial respiration in the ischemic reperfused rat heart

Dietary restriction increases life span and delays the development of age-related diseases in rodents. We have recently demonstrated that chronic dietary restriction is beneficial on recovery of heart function following ischemia. We studied whether the metabolic basis of this benefit is associated with alterations in mitochondrial respiration. Male Wistar rats were assigned to an ad libitum-fed (AL) group and a food restricted (FR) group, in which food intake was reduced to 55% of the amount consumed by the AL group. Following an 8-month period of restricted caloric intake, isolated working hearts perfused with glucose and high levels of fatty acids were subjected to global ischemia followed by reperfusion. At the end of reperfusion, total heart mitochondria was respiration was assessed in the presence of pyruvate, tricarboxylic acid intermediates, and palmitoylcarnitine. Recovery of heart function following ischemia was greater in FR hearts compared to AL hearts. Paralleling these changes in heart function was in increase in state 3 respiration with pyruvate. The respiratory control ratios in the presence of pyruvate and tricarboxylic acid intermediates were higher in FR hearts compared to AL hearts, indicating well-coupled mitochondria. Overall energy production, expressed as the ADP:O ratio and the oxidative phosphorylation rate, was also improved in FR hearts. Our results indicate that the beneficial effect of FR on recovery of heart function following ischemia is associated with changes in mitochondrial respiration.     

绵羊ghrelin基因表达的组织分布和发育性变化

选取2、30、60、90和120日龄的雄性哈萨克羊和新疆细毛羊各6只（无120日龄的哈萨克羊）,测体重后屠宰,采下丘脑、垂体、心脏、肝脏、瘤胃、网胃、瓣胃、皱胃、十二指肠、背最长肌,用RT-PCR和荧光实时定量PCR法检测ghrelin基因表达的组织分布,及其在皱胃中的发育性变化。研究结果表明：（1）品种内各生长时期的体重差异显著（P〈0．05）。雄性哈萨克羊和新疆细毛羊的体重在2日龄时无显著差异（P〉0．05）,30～90日龄间,前者的体重极显著高于后者（P〈0．01）;（2）所检测的各组织中都有ghrelin mRNA分布,但主要在皱胃中表达,其表达量远高于其他组织（P＜0．05）;（3）两品种绵羊皱胃ghrelin基因表达的发育性变化模式基本相似,都随着日龄的增加而呈上升趋势,其中雄性哈萨克羊的表达量在2～60日龄间持续上升,60日龄后趋于水平;雄性新疆细毛羊的表达量在2～90日龄间持续上升,90日龄后趋于水平。研究还发现雄性哈萨克羊皱胃胂relin基因的表达量在2～90日龄间极显著高于新疆细毛羊（P＜0．01）。     

The octanoylated energy regulating hormone ghrelin: An expanded view of ghrelin’s biological interactions and avenues for controlling ghrelin signaling

Ghrelin is a small peptide hormone that requires a unique post-translational modification, serine octanoylation, to bind and activate the GHS-R1a receptor. Initially demonstrated to stimulate hunger and appetite, ghrelin-dependent signaling is implicated in a variety of neurological and physiological processes influencing diseases such as diabetes, obesity, and Prader-Willi syndrome. In addition to its cognate receptor, recent studies have revealed ghrelin interacts with a range of binding partners within the bloodstream. Defining the scope of ghrelin’s interactions within the body, understanding how these interactions work in concert to modulate ghrelin signaling, and developing molecular tools for controlling ghrelin signaling are essential for exploiting ghrelin for therapeutic effect. In this review, we discuss recent findings regarding the biological effects of ghrelin signaling, outline binding partners that control ghrelin trafficking and stability in circulation, and summarize the current landscape of inhibitors targeting ghrelin octanoylation.     

Regulation of hyperphagia in response to varying energy deficits in overwintering juvenile Atlantic salmon

Resident juvenile Atlantic salmon responded to a period of winter food restriction by subsequently increasing appetite when food again became available. This hyperphagy contributed to the restoration of an energy deficit (derived from a biometric estimation of body lipid reserves) incurred during the period of food restriction. The extent of this deficit influenced the duration of the hyperphagic response: those fish incurring the greatest fat losses maintained appetite longer than those with a smaller energy deficit. The initial feeding intensity of fish incurring a wide range of fat losses was found to be similar, indicating that fish were regulating the length as opposed to the intensity of the hyperphagic response in order to restore losses. The ecological implications of the results are discussed in relation to juvenile salmon overwintering strategies.