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1.
Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae 总被引：1，自引：0，他引：1
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. 相似文献
2.
Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging 总被引：4，自引：0，他引：4
T E Johnson 《Science (New York, N.Y.)》1990,249(4971):908-912
A mutation in the age-1 gene of the nematode Caenorhabditis elegans has been shown to result in a 65 percent increase in mean life-span and a 110 percent increase in maximum life-span at 25 degrees. One of the hallmarks of organismic aging and senescent processes is an exponential acceleration of age-specific mortality rate with chronological age. This exponential acceleration is under genetic control: age-1 mutant hermaphrodites show a 50 percent slower rate of acceleration of mortality with chronological age than wild-type strains. Mutant males also show a lengthening of life and a slowing of the rate of acceleration of mortality, although age-1 mutant males still have significantly shorter life-spans than do hermaphrodites of the same genotype. The slower rates of acceleration of mortality are recessive characteristics of the age-1 mutant alleles examined. 相似文献
3.
An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity. 相似文献
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5.
Melov S Ravenscroft J Malik S Gill MS Walker DW Clayton PE Wallace DC Malfroy B Doctrow SR Lithgow GJ 《Science (New York, N.Y.)》2000,289(5484):1567-1569
We tested the theory that reactive oxygen species cause aging. We augmented the natural antioxidant systems of Caenorhabditis elegans with small synthetic superoxide dismutase/catalase mimetics. Treatment of wild-type worms increased their mean life-span by a mean of 44 percent, and treatment of prematurely aging worms resulted in normalization of their life-span (a 67 percent increase). It appears that oxidative stress is a major determinant of life-span and that it can be counteracted by pharmacological intervention. 相似文献
6.
Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase 总被引：4，自引：0，他引：4
Cohen HY Miller C Bitterman KJ Wall NR Hekking B Kessler B Howitz KT Gorospe M de Cabo R Sinclair DA 《Science (New York, N.Y.)》2004,305(5682):390-392
A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells. 相似文献
7.
A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function 总被引：1，自引：0，他引：1
Tatar M Kopelman A Epstein D Tu MP Yin CM Garofalo RS 《Science (New York, N.Y.)》2001,292(5514):107-110
The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue. 相似文献
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9.
Campisi J 《Science (New York, N.Y.)》2000,289(5487):2062-2063
Model organisms such as yeast have proved exceptionally valuable for revealing new information about the molecular pathways involved in the aging of cells. In her Perspective, Campisi comments on new work showing that caloric restriction increases longevity in yeast by activating the SIR2 gene, which alters the compactness of chromatin and thus regulates gene expression (Lin et al.). 相似文献
10.
Genetic studies have elucidated mechanisms that regulate aging, but there has been little progress in identifying drugs that delay aging. Here, we report that ethosuximide, trimethadione, and 3,3-diethyl-2-pyrrolidinone increase mean and maximum life-span of Caenorhabditis elegans and delay age-related declines of physiological processes, indicating that these compounds retard the aging process. These compounds, two of which are approved for human use, are anticonvulsants that modulate neural activity. These compounds also regulated neuromuscular activity in nematodes. These findings suggest that the life-span-extending activity of these compounds is related to the anticonvulsant activity and implicate neural activity in the regulation of aging. 相似文献
11.
Lanza RP Cibelli JB Blackwell C Cristofalo VJ Francis MK Baerlocher GM Mak J Schertzer M Chavez EA Sawyer N Lansdorp PM West MD 《Science (New York, N.Y.)》2000,288(5466):665-669
The potential of cloning depends in part on whether the procedure can reverse cellular aging and restore somatic cells to a phenotypically youthful state. Here, we report the birth of six healthy cloned calves derived from populations of senescent donor somatic cells. Nuclear transfer extended the replicative life-span of senescent cells (zero to four population doublings remaining) to greater than 90 population doublings. Early population doubling level complementary DNA-1 (EPC-1, an age-dependent gene) expression in cells from the cloned animals was 3.5- to 5-fold higher than that in cells from age-matched (5 to 10 months old) controls. Southern blot and flow cytometric analyses indicated that the telomeres were also extended beyond those of newborn (<2 weeks old) and age-matched control animals. The ability to regenerate animals and cells may have important implications for medicine and the study of mammalian aging. 相似文献
12.
黄嘌呤脱氢酶广泛分布在真核生物、细菌和古细菌中,是催化氧化嘌呤、蝶啶和醛类等多种杂环分子的氧化还原酶类,与氮同化、激素代谢、衰老的调控及活性氧产生等过程相关.耐辐射异常球菌(Deinococcus radiodurans R1)具有超强的氧化胁迫抗性和氧保护机制,其基因组含有完整的黄嘌呤脱氢酶编码基因xdhABC.为探... 相似文献
13.
Auxin is a plant hormone that regulates many aspects of plant growth and development. We used a chemical genetics approach to identify SIR1, a regulator of many auxin-inducible genes. The sir1 mutant was resistant to sirtinol, a small molecule that activates many auxin-inducible genes and promotes auxin-related developmental phenotypes. SIR1 is predicted to encode a protein composed of a ubiquitin-activating enzyme E1-like domain and a Rhodanese-like domain homologous to that of prolyl isomerase. We suggest a molecular context for how the auxin signal is propagated to exert its biological effects. 相似文献
14.
Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein 总被引：1，自引：0，他引：1
Clancy DJ Gems D Harshman LG Oldham S Stocker H Hafen E Leevers SJ Partridge L 《Science (New York, N.Y.)》2001,292(5514):104-106
The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult longevity. We found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not a result of impaired oogenesis in chico females, nor was it consistently correlated with increased stress resistance. The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved. 相似文献
15.
Dillin A Hsu AL Arantes-Oliveira N Lehrer-Graiwer J Hsin H Fraser AG Kamath RS Ahringer J Kenyon C 《Science (New York, N.Y.)》2002,298(5602):2398-2401
To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood. 相似文献
16.
[目的]研究花生四烯酸高产突变株的发酵及菌丝老化特性。[方法]对1株经诱变获得的花生四烯酸高产突变株A1．13进行5L罐发酵试验,考察不同培养条件对发酵产物的影响。[结果]碳源一次性过量加入并改变培养温度,可使该菌株花生四烯酸产量提高至602．99mg／L;发酵菌丝体在4℃条件下老化15d后,花生四烯酸产量达885．16mg/L。大豆油、花生油、玉米油、葵花籽油和芝麻油5种植物油均可起到消泡作用,添加浓度4％葵花籽油效果最佳,与对照相比,菌丝生物量和花生四烯酸产量分别提高了124％和22％。[结论]该研究可为突变株A1．13工业化发酵产花生四烯酸提供理论依据和现实参考。 相似文献
17.
依赖于NAD 的组蛋白脱乙酰化酶SIR2对酵母和哺乳动物细胞的存活、衰老、凋亡等生理活动的调节起着重要的作用.利用生物信息学方法对SIR2在水稻中的生物学功能进行研究.结果表明,SRT701和SRT702分别位于第4条和第12条染色体上;它们编码的蛋白均含有N-糖基化、蛋白激酶C磷酸化、酪蛋白激酶Ⅱ磷酸化和豆蔻酰化4个相同的位点;SRT701主要位于细胞核,而SRT702主要位于内质网,它们均有跨膜区,且为疏水性蛋白质,都无信号肽;多序列比对发现植物SIR2家族的SIR2结构域高度保守;电子表达谱分析发现SRT701主要表达于叶片和花序,SRT702表达于整个植物中.利用RT-PCR方法进行检测的结果表明,SRT701在水稻根、茎、叶中均有表达,而SRT702只在叶、茎中有表达,根中没有表达,说明利用生物信息学方法所得的结果只能作为初步预测.水稻SRT701和SRT702器官特异性的表达模式表明它们可能在组织或器官形成中起着重要作用. 相似文献
18.
采用质量浓度为5 g/L的PEG - 6000进行渗透胁迫,利用弯根法筛选拟南芥T-DNA插入突变体库,得到干旱敏感突变体36 -1.该突变体在PEG - 6000渗透胁迫下,种子萌发率、根系长度均低于野生型;盆栽试验表明:水分正常条件下,突变体36 -1与野生型幼苗形态、根冠比、叶片含水量等并无明显差异;干旱条件下,... 相似文献
19.
The insulin/IGF-1 (where IGF-1 is insulin-like growth factor-1) signaling pathway influences longevity, reproduction, and diapause in many organisms. Because of the fundamental importance of this system in animal physiology, we asked when during the animal's life it is required to regulate these different processes. We find that in Caenorhabditis elegans, the pathway acts during adulthood, to relatively advanced ages, to influence aging. In contrast, it regulates diapause during development. In addition, the pathway controls longevity and reproduction independently of one another. Together our findings show that life-span regulation can be dissociated temporally from phenotypes that might seem to decrease the quality of life. 相似文献
20.
抽穗期是水稻的重要农艺性状之一,决定着品种的地区与季节适应性,因而成为水稻育种家考虑的主要目标性状之一。前期克隆了一些控制水稻抽穗期的主效基因,但是对控制水稻抽穗期的调控因子的鉴定还非常有限。通过筛选水稻突变体库,获得一份在长日照条件下(LD)不开花的突变体(non flowering mutant 1,nfm1),其在短日照条件下能够正常开花。利用图位克隆,将Nfm1基因缩小在2个分子标记In Del1与In Del2之间,范围在50 kb区间内,该区间包含4个基因。通过序列测定,确定LOC_Os09g13740为Nfm1的候选基因。在突变体nfm1中,LOC_Os09g13740基因的第六外显子242处丝氨酸突变为异亮氨酸。突变体nfm1等位于已报道的水稻突变体lvp1-1,Nfm1编码一个含有SET结构域的组蛋白甲基转移酶SDG724。值得关注的是,在短日照条件下,突变体nfm1显著地提高每穗粒数,显示LOC_Os09g13740基因的弱表达可能在适应的生态区具有潜在的生产应用潜力,为培育适应不同生态区域的水稻品种提供了参考。 相似文献