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  • 1
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    Timing requirements for insulin/IGF-1 signaling in C. elegans (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-10-26
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dillin, Andrew -- Crawford, Douglas K -- Kenyon, Cynthia -- 5RO1AG11816/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):830-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-0448, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12399591" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Caenorhabditis elegans/genetics/growth & development/metabolism/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; DEAD-box RNA Helicases ; Forkhead Transcription Factors ; Insulin/*physiology ; Insulin-Like Growth Factor I/*physiology ; Life Cycle Stages/physiology ; Longevity ; Mutation ; Oxidative Stress ; RNA Helicases/genetics/physiology ; RNA Interference ; Receptor, Insulin/genetics/*physiology ; Reproduction ; *Signal Transduction ; Temperature ; Transcription Factors/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    Rates of behavior and aging specified by mitochondrial function during development (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-12-10
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dillin, Andrew -- Hsu, Ao-Lin -- Arantes-Oliveira, Nuno -- Lehrer-Graiwer, Joshua -- Hsin, Honor -- Fraser, Andrew G -- Kamath, Ravi S -- Ahringer, Julie -- Kenyon, Cynthia -- 054523/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2002 Dec 20;298(5602):2398-401. Epub 2002 Dec 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471266" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Behavior, Animal ; Caenorhabditis elegans/cytology/growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/metabolism ; Cell Size ; *Electron Transport ; Electron Transport Complex I ; Electron Transport Complex III/genetics/metabolism ; Electron Transport Complex IV/genetics/metabolism ; Endoribonucleases/genetics/metabolism ; Feeding Behavior ; Forkhead Transcription Factors ; Iron-Sulfur Proteins/genetics/metabolism ; Longevity ; Mitochondria/*metabolism ; Mitochondrial Proton-Translocating ATPases/genetics/metabolism ; Movement ; NADH Dehydrogenase/genetics/metabolism ; NADH, NADPH Oxidoreductases/genetics/metabolism ; *Oxygen Consumption ; Phenotype ; RNA Interference ; RNA, Double-Stranded/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Receptor, Insulin/genetics/metabolism ; Ribonuclease III ; Transcription Factors/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    A conserved ubiquitination pathway determines longevity in response to diet restriction (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-06-26
    Description: Dietary restriction extends longevity in diverse species, suggesting that there is a conserved mechanism for nutrient regulation and prosurvival responses. Here we show a role for the HECT (homologous to E6AP carboxy terminus) E3 ubiquitin ligase WWP-1 as a positive regulator of lifespan in Caenorhabditis elegans in response to dietary restriction. We find that overexpression of wwp-1 in worms extends lifespan by up to 20% under conditions of ad libitum feeding. This extension is dependent on the FOXA transcription factor pha-4, and independent of the FOXO transcription factor daf-16. Reduction of wwp-1 completely suppresses the extended longevity of diet-restricted animals. However, the loss of wwp-1 does not affect the long lifespan of animals with compromised mitochondrial function or reduced insulin/IGF-1 signalling. Overexpression of a mutant form of WWP-1 lacking catalytic activity suppresses the increased lifespan of diet-restricted animals, indicating that WWP-1 ubiquitin ligase activity is essential for longevity. Furthermore, we find that the E2 ubiquitin conjugating enzyme, UBC-18, is essential and specific for diet-restriction-induced longevity. UBC-18 interacts with WWP-1 and is required for the ubiquitin ligase activity of WWP-1 and the extended longevity of worms overexpressing wwp-1. Taken together, our results indicate that WWP-1 and UBC-18 function to ubiquitinate substrates that regulate diet-restriction-induced longevity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carrano, Andrea C -- Liu, Zheng -- Dillin, Andrew -- Hunter, Tony -- AG 027463/AG/NIA NIH HHS/ -- AG 032560/AG/NIA NIH HHS/ -- CA 14195/CA/NCI NIH HHS/ -- CA 54418/CA/NCI NIH HHS/ -- CA 82683/CA/NCI NIH HHS/ -- DK 070696/DK/NIDDK NIH HHS/ -- P01 CA054418/CA/NCI NIH HHS/ -- P01 CA054418-110010/CA/NCI NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- P30 CA014195-35/CA/NCI NIH HHS/ -- R01 AG027463/AG/NIA NIH HHS/ -- R01 AG027463-01A2/AG/NIA NIH HHS/ -- R01 CA082683/CA/NCI NIH HHS/ -- R01 CA082683-07/CA/NCI NIH HHS/ -- R01 CA082683-08/CA/NCI NIH HHS/ -- R01 DK070696/DK/NIDDK NIH HHS/ -- R01 DK070696-04/DK/NIDDK NIH HHS/ -- R21 AG032560/AG/NIA NIH HHS/ -- R21 AG032560-01/AG/NIA NIH HHS/ -- England -- Nature. 2009 Jul 16;460(7253):396-9. doi: 10.1038/nature08130. Epub 2009 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553937" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; *Caloric Restriction ; DNA-Binding Proteins/metabolism ; Heat-Shock Response ; Ligases/genetics/*metabolism ; Longevity/*physiology ; Protein Binding ; Receptors, Nicotinic/genetics/metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Medicine. The yin-yang of sirtuins (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-07-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dillin, Andrew -- Kelly, Jeffery W -- New York, N.Y. -- Science. 2007 Jul 27;317(5837):461-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. dillin@salk.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17656709" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Autophagy ; Cell Line, Tumor ; Disease Models, Animal ; Drosophila melanogaster ; Humans ; Neurodegenerative Diseases/physiopathology ; Parkinson Disease/drug therapy/pathology/*physiopathology ; RNA Interference ; Rats ; Signal Transduction ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/*antagonists & inhibitors/genetics/metabolism/*physiology ; Transfection ; alpha-Synuclein/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span (2014)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2014-10-18
    Description: The conserved heat shock transcription factor-1 (HSF-1) is essential to cellular stress resistance and life-span determination. The canonical function of HSF-1 is to regulate a network of genes encoding molecular chaperones that protect proteins from damage caused by extrinsic environmental stress or intrinsic age-related deterioration. In Caenorhabditis elegans, we engineered a modified HSF-1 strain that increased stress resistance and longevity without enhanced chaperone induction. This health assurance acted through the regulation of the calcium-binding protein PAT-10. Loss of pat-10 caused a collapse of the actin cytoskeleton, stress resistance, and life span. Furthermore, overexpression of pat-10 increased actin filament stability, thermotolerance, and longevity, indicating that in addition to chaperone regulation, HSF-1 has a prominent role in cytoskeletal integrity, ensuring cellular function during stress and aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403873/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403873/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baird, Nathan A -- Douglas, Peter M -- Simic, Milos S -- Grant, Ana R -- Moresco, James J -- Wolff, Suzanne C -- Yates, John R 3rd -- Manning, Gerard -- Dillin, Andrew -- 1K99AG042495-01A1/AG/NIA NIH HHS/ -- 5P41RR011823-17/RR/NCRR NIH HHS/ -- 8 P41 GM103533-17/GM/NIGMS NIH HHS/ -- P01 AG031097/AG/NIA NIH HHS/ -- P40 OD010440/OD/NIH HHS/ -- P41 GM103533/GM/NIGMS NIH HHS/ -- R01AG027463-04/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Oct 17;346(6207):360-3. doi: 10.1126/science.1253168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA. ; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA. ; Scripps Research Institute, La Jolla, CA 92037, USA. ; Genentech, South San Francisco, CA 94080, USA. ; Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA. dillin@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25324391" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/metabolism ; Animals ; Caenorhabditis elegans/genetics/*physiology ; Caenorhabditis elegans Proteins/genetics/*pharmacology/*physiology ; Cytoskeleton/*physiology/ultrastructure ; Heat-Shock Response/genetics/*physiology ; Hot Temperature ; *Longevity ; RNA Interference ; Transcription Factors/genetics/*physiology ; Troponin C/genetics/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Roles for ORC in M phase and S phase (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-03-28
    Description: The origin recognition complex (ORC), a six-subunit protein, functions as the replication initiator in the yeast Saccharomyces cerevisiae. Initiation depends on the assembly of the prereplication complex in late M phase and activation in S phase. One subunit of ORC, Orc5p, was required at G1/S and in early M phase. Asynchronous cells with a temperature-sensitive orc5-1 allele arrested in early M phase. In contrast, cells that were first synchronized in M phase, shifted to the restrictive temperature, and then released from the block arrested at the G1/S boundary. The G1/S arrest phenotype could not be suppressed by introducing wild-type Orc5p during G1. Although all orc2 and orc5 mutations were recessive in the conventional sense, this dominant phenotype was shared with other orc5 alleles and an orc2 allele. The dominant inhibition to cell-cycle progression exhibited by the orc mutants was restricted to the nucleus, suggesting that chromosomes with mutant ORC complexes were capable of sending a signal that blocked initiation on chromosomes containing functional origins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dillin, A -- Rine, J -- GM-31105/GM/NIGMS NIH HHS/ -- P30ESO1896-12/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1998 Mar 13;279(5357):1733-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, University of California at Berkeley, 401 Barker Hall, Berkeley, CA 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9497294" target="_blank"〉PubMed〈/a〉
    Keywords: CDC28 Protein Kinase, S cerevisiae/metabolism ; *Cell Cycle Proteins ; Cell Nucleus/physiology ; Chromosomes, Fungal/physiology ; Crosses, Genetic ; *DNA Replication ; DNA, Fungal/biosynthesis ; DNA-Binding Proteins/genetics/*physiology ; Fungal Proteins/physiology ; Genes, Fungal ; *Mitosis ; Mutation ; Origin Recognition Complex ; Phenotype ; *S Phase ; Saccharomyces cerevisiae/*cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins ; Temperature
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Regulation of life-span by germ-line stem cells in Caenorhabditis elegans (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-01-19
    Description: The germ line of the nematode Caenorhabditis elegans influences life-span; when the germ-line precursor cells are removed, life-span is increased dramatically. We find that neither sperm, nor oocytes, nor meiotic precursor cells are responsible for this effect. Rather life-span is influenced by the proliferating germ-line stem cells. These cells, as well as a downstream transcriptional regulator, act in the adult to influence aging, indicating that the aging process remains plastic during adulthood. We propose that the germ-line stem cells affect life-span by influencing the production of, or the response to, a steroid hormone that promotes longevity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arantes-Oliveira, Nuno -- Apfeld, Javier -- Dillin, Andrew -- Kenyon, Cynthia -- New York, N.Y. -- Science. 2002 Jan 18;295(5554):502-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143-0448, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11799246" target="_blank"〉PubMed〈/a〉
    Keywords: *Aging ; Animals ; Caenorhabditis elegans/*cytology/genetics/growth & development/*physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Cell Differentiation ; Cell Division ; Female ; Forkhead Transcription Factors ; Genes, Helminth ; Germ Cells/*cytology/physiology ; *Longevity ; Male ; Meiosis ; Mitosis ; Mutation ; Oxidative Stress ; Stem Cells/*physiology ; Temperature ; Transcription Factors/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Increased proteasome activity in human embryonic stem cells is regulated by PSMD11 (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-09-14
    Description: Embryonic stem cells can replicate continuously in the absence of senescence and, therefore, are immortal in culture. Although genome stability is essential for the survival of stem cells, proteome stability may have an equally important role in stem-cell identity and function. Furthermore, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. Therefore, a firm understanding of how stem cells maintain their proteome is of central importance. Here we show that human embryonic stem cells (hESCs) exhibit high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11 (known as RPN-6 in Caenorhabditis elegans) and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. FOXO4, an insulin/insulin-like growth factor-I (IGF-I) responsive transcription factor associated with long lifespan in invertebrates, regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Proteasome inhibition in hESCs affects the expression of pluripotency markers and the levels of specific markers of the distinct germ layers. Our results suggest a new regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates to hESC function and identity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vilchez, David -- Boyer, Leah -- Morantte, Ianessa -- Lutz, Margaret -- Merkwirth, Carsten -- Joyce, Derek -- Spencer, Brian -- Page, Lesley -- Masliah, Eliezer -- Berggren, W Travis -- Gage, Fred H -- Dillin, Andrew -- R37 AG018440/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Sep 13;489(7415):304-8. doi: 10.1038/nature11468.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22972301" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation ; Cell Line ; Embryonic Stem Cells/drug effects/*enzymology/metabolism ; HEK293 Cells ; Humans ; Pluripotent Stem Cells/cytology/metabolism ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors ; Protein Subunits/metabolism ; Transcription Factors/metabolism ; Up-Regulation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 9
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    Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-02-19
    Description: Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress. Here we show that both AMPK and calcineurin modulate longevity exclusively through post-translational modification of CRTC-1, the sole C. elegans CRTC. We demonstrate that CRTC-1 is a direct AMPK target, and interacts with the CREB homologue-1 (CRH-1) transcription factor in vivo. The pro-longevity effects of activating AMPK or deactivating calcineurin decrease CRTC-1 and CRH-1 activity and induce transcriptional responses similar to those of CRH-1 null worms. Downregulation of crtc-1 increases lifespan in a crh-1-dependent manner and directly reducing crh-1 expression increases longevity, substantiating a role for CRTCs and CREB in ageing. Together, these findings indicate a novel role for CRTCs and CREB in determining lifespan downstream of AMPK and calcineurin, and illustrate the molecular mechanisms by which an evolutionarily conserved pathway responds to low energy to increase longevity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098900/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098900/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mair, William -- Morantte, Ianessa -- Rodrigues, Ana P C -- Manning, Gerard -- Montminy, Marc -- Shaw, Reuben J -- Dillin, Andrew -- AG027463/AG/NIA NIH HHS/ -- AG031097/AG/NIA NIH HHS/ -- CA14195/CA/NCI NIH HHS/ -- P01 CA120964/CA/NCI NIH HHS/ -- R01 AG027463/AG/NIA NIH HHS/ -- R01 AG027463-01A2/AG/NIA NIH HHS/ -- R01 AG027463-02/AG/NIA NIH HHS/ -- R01 AG027463-03/AG/NIA NIH HHS/ -- R01 AG027463-04/AG/NIA NIH HHS/ -- R01 DK070696/DK/NIDDK NIH HHS/ -- R01 DK070696-01/DK/NIDDK NIH HHS/ -- R01 DK070696-02/DK/NIDDK NIH HHS/ -- R01 DK070696-03/DK/NIDDK NIH HHS/ -- R01 DK070696-04/DK/NIDDK NIH HHS/ -- R01 DK070696-05/DK/NIDDK NIH HHS/ -- R01 DK080425/DK/NIDDK NIH HHS/ -- R01 HG004164/HG/NHGRI NIH HHS/ -- R01 HG004164-03/HG/NHGRI NIH HHS/ -- R01 HG004164-04/HG/NHGRI NIH HHS/ -- R01DK080425/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 17;470(7334):404-8. doi: 10.1038/nature09706.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21331044" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/*metabolism ; Aging/metabolism/physiology ; Animals ; Caenorhabditis elegans/enzymology/genetics/metabolism/*physiology ; Caenorhabditis elegans Proteins/biosynthesis/chemistry/genetics/*metabolism ; Calcineurin/*metabolism ; Calcineurin Inhibitors ; Cyclic AMP Response Element-Binding Protein/biosynthesis/*metabolism ; Down-Regulation ; Energy Metabolism ; Enzyme Activation ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Longevity/genetics/*physiology ; Phosphorylation ; Protein-Serine-Threonine Kinases/metabolism ; Trans-Activators/chemistry/deficiency/genetics/*metabolism ; Transcription Factors/biosynthesis/*metabolism ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    RPN-6 determines C. elegans longevity under proteotoxic stress conditions (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-08-28
    Description: Organisms that protect their germ-cell lineages from damage often do so at considerable cost: limited metabolic resources become partitioned away from maintenance of the soma, leaving the ageing somatic tissues to navigate survival amid an environment containing damaged and poorly functioning proteins. Historically, experimental paradigms that limit reproductive investment result in lifespan extension. We proposed that germline-deficient animals might exhibit heightened protection from proteotoxic stressors in somatic tissues. We find that the forced re-investment of resources from the germ line to the soma in Caenorhabditis elegans results in elevated somatic proteasome activity, clearance of damaged proteins and increased longevity. This activity is associated with increased expression of rpn-6, a subunit of the 19S proteasome, by the FOXO transcription factor DAF-16. Ectopic expression of rpn-6 is sufficient to confer proteotoxic stress resistance and extend lifespan, indicating that rpn-6 is a candidate to correct deficiencies in age-related protein homeostasis disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vilchez, David -- Morantte, Ianessa -- Liu, Zheng -- Douglas, Peter M -- Merkwirth, Carsten -- Rodrigues, Ana P C -- Manning, Gerard -- Dillin, Andrew -- R01 AG042679/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Sep 13;489(7415):263-8. doi: 10.1038/nature11315.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22922647" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*metabolism/physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Separation ; Female ; Forkhead Transcription Factors ; Gene Expression Regulation ; Germ Cells/cytology/metabolism ; Heat-Shock Response/genetics ; Homeostasis/radiation effects ; Longevity/genetics/*physiology/radiation effects ; Male ; Mutation/genetics ; Oxidative Stress/physiology ; Peptides/metabolism ; Proteasome Endopeptidase Complex/chemistry/genetics/*metabolism ; Stress, Physiological/*physiology/radiation effects ; Transcription Factors/metabolism ; Ultraviolet Rays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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