共查询到20条相似文献，搜索用时 88 毫秒
1.
Lamming DW Latorre-Esteves M Medvedik O Wong SN Tsang FA Wang C Lin SJ Sinclair DA 《Science (New York, N.Y.)》2005,309(5742):1861-1864
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. 相似文献
2.
Kaeberlein M Steffen KK Hu D Dang N Kerr EO Tsuchiya M Fields S Kennedy BK 《Science (New York, N.Y.)》2006,312(5778):1312; author reply 1312
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. 相似文献
3.
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. 相似文献
4.
Anderson RM Latorre-Esteves M Neves AR Lavu S Medvedik O Taylor C Howitz KT Santos H Sinclair DA 《Science (New York, N.Y.)》2003,302(5653):2124-2126
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. 相似文献
5.
Kaeberlein M Powers RW Steffen KK Westman EA Hu D Dang N Kerr EO Kirkland KT Fields S Kennedy BK 《Science (New York, N.Y.)》2005,310(5751):1193-1196
Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae. From a large-scale analysis of 564 single-gene-deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of tor1D or sch9D cells failed to further increase life span and, like calorie restriction, deletion of either SCH9 or TOR1 increased life span independent of the Sir2 histone deacetylase. We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast. 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.
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS 总被引：2，自引：0，他引：2
Nisoli E Tonello C Cardile A Cozzi V Bracale R Tedesco L Falcone S Valerio A Cantoni O Clementi E Moncada S Carruba MO 《Science (New York, N.Y.)》2005,310(5746):314-317
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. 相似文献
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9.
Domergue R Castaño I De Las Peñas A Zupancic M Lockatell V Hebel JR Johnson D Cormack BP 《Science (New York, N.Y.)》2005,308(5723):866-870
10.
Axonal degeneration is an active program of self-destruction that is observed in many physiological and pathological settings. In Wallerian degeneration slow (wlds) mice, Wallerian degeneration in response to axonal injury is delayed because of a mutation that results in overexpression of a chimeric protein (Wlds) composed of the ubiquitin assembly protein Ufd2a and the nicotinamide adenine dinucleotide (NAD) biosynthetic enzyme Nmnat1. We demonstrate that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein. Furthermore, we demonstrate that SIRT1, a mammalian ortholog of Sir2, is the downstream effector of increased Nmnat activity that leads to axonal protection. These findings suggest that novel therapeutic strategies directed at increasing the supply of NAD and/or Sir2 activation may be effective for treatment of diseases characterized by axonopathy and neurodegeneration. 相似文献
11.
Selman C Lingard S Gems D Partridge L Withers DJ 《Science (New York, N.Y.)》2008,320(5879):1012; author reply 1012
Taguchi et al. (Reports, 20 July 2007, p. 369) reported that mice heterozygous for a null mutation in insulin receptor substrate-2 (Irs2) display a 17% increase in median life span. However, using the same mouse model, we find no evidence for life-span extension and suggest that the findings of Taguchi et al. were due to atypical life-span profiles in their study animals. 相似文献
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13.
Carbonylated proteins were visualized in single cells of the budding yeast Saccharomyces cerevisiae, revealing that they accumulate with replicative age. Furthermore, carbonylated proteins were not inherited by daughter cells during cytokinesis. Mother cells of a yeast strain lacking the sir2 gene, a life-span determinant, failed to retain oxidatively damaged proteins during cytokinesis. These findings suggest that a genetically determined, Sir2p-dependent asymmetric inheritance of oxidatively damaged proteins may contribute to free-radical defense and the fitness of newborn cells. 相似文献
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15.
Aging is genetically determined and environmentally modulated. In a study of longevity in the adult fruit fly, Drosophila melanogaster, we found that five independent P-element insertional mutations in a single gene resulted in a near doubling of the average adult life-span without a decline in fertility or physical activity. Sequence analysis revealed that the product of this gene, named Indy (for I'm not dead yet), is most closely related to a mammalian sodium dicarboxylate cotransporter-a membrane protein that transports Krebs cycle intermediates. Indy was most abundantly expressed in the fat body, midgut, and oenocytes: the principal sites of intermediary metabolism in the fly. Excision of the P element resulted in a reversion to normal life-span. These mutations may create a metabolic state that mimics caloric restriction, which has been shown to extend life-span. 相似文献
16.
Meléndez A Tallóczy Z Seaman M Eskelinen EL Hall DH Levine B 《Science (New York, N.Y.)》2003,301(5638):1387-1391
Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans. 相似文献
17.
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
18.
Dietary restriction (DR) increases life-span in organisms from yeast to mammals, presumably by slowing the accumulation of aging-related damage. Here we show that in Drosophila, DR extends life-span entirely by reducing the short-term risk of death. Two days after the application of DR at any age for the first time, previously fully fed flies are no more likely to die than flies of the same age that have been subjected to long-term DR. DR of mammals may also reduce short-term risk of death, and hence DR instigated at any age could generate a full reversal of mortality. 相似文献
19.
枸杞提取物对果蝇寿命及SOD和MDA的影响 总被引：2，自引：0，他引：2
[目的]探讨枸杞提取物在延缓衰老方面的作用。[方法]以黑腹果蝇为试材,收集8h内羽化的雌雄果蝇成虫,置于用枸杞提取液含0.01%、0.03%、0.09%和0.27%4种浓度配制的培养基上于25℃下进行培养,研究枸杞提取液对果蝇寿命及果蝇体内超氧化物歧化酶（SOD）和丙二醛（MDA）的影响。[结果]与对照组相比,枸杞提取物0.09%和0.27%处理组可分别延长雌性果蝇半数死亡期2和4.4d,平均寿命2.6和3.2d,平均最高寿命2.8和5.8d,可分别延长雄性果蝇半数死亡期2.1和4.1d,平均寿命2.5和2.0d（P〈0.05）,平均最高寿命5.5和4.5d（P〈0.05）;枸杞提取物0.03%、0.09%和0.27%处理组可显著提高雌果蝇的SOD活性,降低雌、雄果蝇的MDA含量。[结论]枸杞提取物具有高度抗氧化能力,可清除体内自由基,使果蝇寿命延长。 相似文献
20.
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