共查询到20条相似文献，搜索用时 46 毫秒
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The identification and study of long-lived mutant animals has provided valuable insights into the mechanisms that limit the life-span of organisms. Findings with the gene SIR2 suggest that the rate of aging can be regulated under certain conditions. Indeed, increased expression of SIR2 lengthens life-span by acting on biological processes that promote survival under conditions of scarcity. In addition, studies of mutant strains of Caenorhabditis elegans, in particular daf-2, clk-1, and isp-1 mutants, suggest that the biology of reactive oxygen species in the mitochondria and elsewhere might be the main determinant of life-span in this organism. Thus, the aging process may be more specific than previously anticipated on evolutionary grounds. 相似文献
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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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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
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Dong MQ Venable JD Au N Xu T Park SK Cociorva D Johnson JR Dillin A Yates JR 《Science (New York, N.Y.)》2007,317(5838):660-663
DAF-2, an insulin receptor-like protein, regulates metabolism, development, and aging in Caenorhabditis elegans. In a quantitative proteomic study, we identified 86 proteins that were more or less abundant in long-lived daf-2 mutant worms than in wild-type worms. Genetic studies on a subset of these proteins indicated that they act in one or more processes regulated by DAF-2, including entry into the dauer developmental stage and aging. In particular, we discovered a compensatory mechanism activated in response to reduced DAF-2 signaling, which involves the protein phosphatase calcineurin. 相似文献
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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
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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
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Pennisi E 《Science (New York, N.Y.)》2000,290(5499):2048
On page 2137, a research team reports the discovery of a gene that, when altered, can double the life-span of fruit flies and may one day offer the promise of perpetual youth. Preliminary data suggest that the protein encoded by this gene transports and recycles metabolic byproducts. The researchers think that defects in the gene can lead to production of a protein that renders metabolism less efficient; as a result the body functions as if the fruit fly were dieting, even though its eating habits are unchanged. The work may lead to a better understanding of how metabolism plays into aging. 相似文献
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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
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Wu H Kanatous SB Thurmond FA Gallardo T Isotani E Bassel-Duby R Williams RS 《Science (New York, N.Y.)》2002,296(5566):349-352
Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis, up-regulation of mitochondrial enzymes involved in fatty acid metabolism and electron transport, and reduced susceptibility to fatigue during repetitive contractions. CaMK induced expression of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), a master regulator of mitochondrial biogenesis in vivo, and activated the PGC-1 gene promoter in cultured myocytes. Thus, a calcium-regulated signaling pathway controls mitochondrial biogenesis in mammalian cells. 相似文献
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Transcriptomic analysis elucidates the enhanced skeletal muscle mass,reduced fat accumulation,and metabolically benign liver in human follistatin-344 transgenic pigs 
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下载免费PDF全文 LONG Ke-ren LI Xiao-kai ZHANG Ruo-wei GU Yi-ren DU Min-jie XING Xiang-yang DU Jia-xiang MAI Miao-miao WANG Jing JIN Long TANG Qian-zi HU Si-lu MA Ji-deng WANG Xun PAN Deng-ke LI Ming-zhou 《农业科学学报》2022,21(9):2675-2690
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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
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TIMP2 promotes intramuscular fat deposition by regulating the extracellular matrix in chicken 下载免费PDF全文
下载免费PDF全文 CUI Huan-xian LUO Na GUO Li-ping LIU Lu XING Si-yuan ZHAO Gui-ping WEN Jie 《农业科学学报》2023,22(3):853-863
The interaction between myocytes and intramuscular adipocytes is a hot scientific topic. Using a co-culture system, this study aims to investigate the regulation of intramuscular fat deposition in chicken muscle tissue through the interaction between myocyte and adipocyte and identify important intermediary regulatory factors. Our proteomics data showed that the protein expression of tissue inhibitor of metalloproteinases 2 (TIMP2) increased significantly in the culture medium of the co-culture system, and the content of lipid droplets was more in the co-culture intramuscular adipocytes. In addition, TIMP2 was significantly upregulated (P<0.01) in muscle tissue of individuals with high intramuscular fat content. Weighted gene co-expression network analysis revealed that TIMP2 was mainly involved in the extracellular matrix receptor interaction signaling pathway and its expression was significantly correlated with triglyceride, intramuscular fat, C14:0, C14:1, C16:0, C16:1, and C18:1n9C levels. Additionally, TIMP2 was co-expressed with various representative genes related to lipid metabolism (such as ADIPOQ, SCD, ELOVL5, ELOVL7, and LPL), as well as certain genes involved in extracellular matrix receptor interaction (such as COL1A2, COL4A2, COL5A1, COL6A1, and COL6A3), which are also significantly upregulated (P<0.05 or P<0.01) in muscle tissue of individuals with high intramuscular fat content. Our findings reveal that TIMP2 promotes intramuscular fat deposition in muscle tissue through the extracellular matrix receptor interaction signaling pathway. 相似文献
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The endocrine regulation of aging by insulin-like signals 总被引：1，自引：0，他引：1
Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism. 相似文献
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Milan D Jeon JT Looft C Amarger V Robic A Thelander M Rogel-Gaillard C Paul S Iannuccelli N Rask L Ronne H Lundström K Reinsch N Gellin J Kalm E Roy PL Chardon P Andersson L 《Science (New York, N.Y.)》2000,288(5469):1248-1251
A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis. 相似文献