Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS

Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression of sirtuin 1. These effects were strongly attenuated in eNOS null-mutant mice. Thus, nitric oxide plays a fundamental role in the processes induced by calorie restriction and may be involved in the extension of life span in mammals.     

Comment on "HST2 mediates SIR2-independent life-span extension by calorie restriction"

Calorie restriction (CR) increases life span in yeast independently of Sir2. Lamming et al. (Reports, 16 September 2005, p. 1861) recently proposed that Sir2-independent life-span extension by CR is mediated by the Sir2 paralogs Hst1 and Hst2. Contradictory to this, we find that CR greatly increases life span in cells lacking Sir2, Hst1, and Hst2, which suggests that CR is not mediated by Sir2, Hst2, or Hst1.     

HST2 mediates SIR2-independent life-span extension by calorie restriction

Calorie restriction (CR) extends the life span of numerous species, from yeast to rodents. Yeast Sir2 is a nicotinamide adenine dinucleotide (NAD+-dependent histone deacetylase that has been proposed to mediate the effects of CR. However, this hypothesis has been challenged by the observation that CR can extend yeast life span in the absence of Sir2. Here, we show that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span. These findings demonstrate that the maintenance of DNA stability is critical for yeast life-span extension by CR and suggest that, in higher organisms, multiple members of the Sir2 family may regulate life span in response to diet.     

Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity

Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo.     

Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae

Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.     

Yeast life-span extension by calorie restriction is independent of NAD fluctuation

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+ levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.     

培养基成分对雌果蝇寿命的影响

[目的]探讨各培养基成分对雌果蝇寿命的影响。[方法]通过测定雌果蝇的寿命、鲜重及超氧化物歧化酶(SOD)活性,研究了不同培养基成分对雌果蝇寿命及体重的影响。[结果]含酵母粉的培养基显著延长了雌果蝇的寿命,而浓度变化对雌果蝇的寿命没有显著影响;不同浓度白砂糖对雌果蝇寿命的影响呈现倒钟型的曲线,当培养基中糖浓度为40.5 g/L处果蝇出现寿命最长;若糖浓度过低和过高,都不利于果蝇的生长,存活率呈急剧下降趋势;果蝇鲜重随着糖浓度的升高出现下降的趋势;不同糖浓度下SOD活性的变化并没有出现随寿命延长而呈逐渐升高的趋势。[结论]酵母粉浓度变化对处女蝇的寿命延长无显著影响,一定糖浓度使果蝇处于饥饿状态,寿命最长。     

酵母CFD1基因缺失菌株构建及其对复制寿命的影响

目的测定CFD1基因缺失对酿酒酵母复制寿命的影响。方法运用基因同源重组技术构建单基因缺失酵母菌株,利用光学显微镜检测酵母细胞的复制寿命。结果与野生型酵母菌株（29.29±8.71代对比,CFD1基因缺失酵母菌株复制寿命（27.27±8.01）代有所变短,但差异无统计学意义。结论 CFD1基因缺失不影响酿酒酵母的复制寿命。）     

Transgenic mice with a reduced core body temperature have an increased life span

Reduction of core body temperature has been proposed to contribute to the increased life span and the antiaging effects conferred by calorie restriction (CR). Validation of this hypothesis has been difficult in homeotherms, primarily due to a lack of experimental models. We report that transgenic mice engineered to overexpress the uncoupling protein 2 in hypocretin neurons (Hcrt-UCP2) have elevated hypothalamic temperature. The effects of local temperature elevation on the central thermostat resulted in a 0.3 degrees to 0.5 degrees C reduction of the core body temperature. Fed ad libitum, Hcrt-UCP2 transgenic mice had the same caloric intake as their wild-type littermates but had increased energy efficiency and a greater median life span (12% increase in males; 20% increase in females). Thus, modest, sustained reduction of core body temperature prolonged life span independent of altered diet or CR.     

Mutations that increase the life span of C. elegans inhibit tumor growth

Mutations in gld-1 cause lethal germline tumors in the nematode Caenorhabditis elegans. We find that a wide variety of mutations that extend C. elegans' life span confer resistance to these tumors. The long life spans of daf-2/insulin-receptor mutants were not shortened at all by gld-1 mutations; we attribute this finding to decreased cell division and increased DAF-16/p53-dependent apoptosis within the tumors. Mutations that increase life span by restricting food intake or inhibiting respiration did not affect apoptosis but reduced tumor cell division. Unexpectedly, none of these longevity mutations affected mitosis in normal germlines; this finding suggests that cellular changes that lead to longevity preferentially antagonize tumor cell growth.     

Regulation of Drosophila life span by olfaction and food-derived odors

Smell is an ancient sensory system present in organisms from bacteria to humans. In the nematode Caenorhabditis elegans, gustatory and olfactory neurons regulate aging and longevity. Using the fruit fly, Drosophila melanogaster, we showed that exposure to nutrient-derived odorants can modulate life span and partially reverse the longevity-extending effects of dietary restriction. Furthermore, mutation of odorant receptor Or83b resulted in severe olfactory defects, altered adult metabolism, enhanced stress resistance, and extended life span. Our findings indicate that olfaction affects adult physiology and aging in Drosophila, possibly through the perceived availability of nutritional resources, and that olfactory regulation of life span is evolutionarily conserved.     

石斛多糖对延缓秀丽隐杆线虫衰老作用的影响

石斛是中国传统中药材,其多糖含量丰富,具有提高免疫力、抗氧化、延缓衰老等多种功效。本文以多糖含量丰富的铁皮石斛、细茎石斛和鼓槌石斛为对象,探讨了石斛多糖对模式生物秀丽隐杆线虫寿命、产卵量、运动行为能力、热应激能力等的影响。结果表明：三种石斛多糖在不影响秀丽隐杆线虫正常生殖能力的条件下显著延长线虫的平均寿命和最长寿命,其中80mg/L的细茎石斛多糖与对照组相比,平均寿命提高了33.2%;不同浓度的石斛多糖能明显提升线虫的运动能力,其头部摆动频率、身体弯曲频率、热应激能力均随着多糖浓度的升高而增加,与延长线虫寿命正相关。论文结果为阐述石斛多糖延缓衰老功能的作用机理,更好地开发利用石斛提供理论依据。     

稻瘟菌蛋白激发子在酵母双杂交系统中的自激活检测

利用PCR方法扩增稻瘟菌蛋白激发子基因pemG1,并在其上下游分别引入酶切位点EcoRI和XhoI,经双酶切后与诱饵质粒载体pLexA连接构建重组诱饵质粒pLexA-PEMG1,将该重组诱饵质粒转入酵母菌株EGY48[p8op-lacZ]中进行β-半乳糖苷酶整板分析检测自激活。结果表明,成功构建了重组诱饵质粒pLexA-PEMG1,并且其无自激活报告基因作用,对酵母菌株也无毒性作用。这说明该重组诱饵质粒可用于酵母双杂交系统,为筛选番茄cDNA文库获得诱饵蛋白PemG1的相互作用蛋白奠定了基础。     

Extended longevity in mice lacking the insulin receptor in adipose tissue

Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of approximately 134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.     

食料和温湿度对刺槐叶瘿蚊广腹细蜂寿命的影响

[目的]提高刺槐叶瘿蚊广腹细蜂的繁殖率。[方法]设置不同组合的营养源和不同梯度水平的温、湿度,研究其对刺槐叶瘿蚊广腹细蜂寿命的影响。[结果]葡萄糖、蔗糖、蜂蜜、清水较对照均能延长广腹细蜂的寿命,蜂王浆、酵母粉、牛肉膏较对照均不能延长广腹细蜂的寿命。在69%相对湿度下,18、23、33℃对广腹细蜂寿命均无明显影响,寿命在27～28h,显著高于28和38℃下的寿命（22和10h）。在温度28℃下,清水处理保湿、50%相对湿度、90%相对湿度条件下,差异不显著,但与80%、69%、61%、39%、31%相对湿度条件相比差异显著。清水保湿条件下,寿命为36h。[结论]食料和温湿度对刺槐叶瘿蚊广腹细蜂的寿命均有影响。     

Increase in activity during calorie restriction requires Sirt1

Sir2 (silent information regulator 2) is a nicotinamide adenine dinucleotide-dependent deacetylase required for longevity due to calorie restriction in yeast and Drosophila. In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice.     

水稻脂质氧化酶同工酶种质储藏特性的研究

对水稻脂质氧化酶(LOX)同工酶缺失的单体及聚合体人工老化实验研究表明:不同LOX的缺失突变体之间,以LOX-1,LOX-2、LOX-3全缺的D1308、D1311的发芽率始终最高,老化指数最低;LOX-1缺失所造成的影响要大于LOX-2缺失和LOX-3缺失。LOX缺失的单体及聚合体具有较好的储藏特性,LOX的缺失对保持种子生活力和延缓稻谷陈化变质具有重要的作用。进一步的分析认为LOX-1的缺失阻断或延缓了LOX-2和LOX-3所启动的脂质过氧化反应,从而延缓了稻谷的陈化变质,减轻种子生活力的下降。LOX-1可能是控制稻谷陈化变质和种子衰老的关键基因。