Diverse Caenorhabditis elegans genes that are upregulated in dauer larvae also show elevated transcript levels in long-lived, aged, or starved adults.

Under adverse conditions, the nematode Caenorhabditis elegans undergoes reversible developmental arrest as dauer larvae, an alternative third larval stage adapted for dispersal and long-term survival. Following such arrest, which may exceed three times their usual life-span, worms resume development to form reproductive adults of normal subsequent longevity. Mutations of genes in the dauer-formation (daf) pathway can extend life-span two- to fourfold, even in adults that mature without diapause. To identify transcript-level changes that might contribute to extended survival, we prepared a subtractive cDNA library of messages more abundant in dauer than in non-dauer (L3) larvae. Six genes were confirmed as three- to ninefold upregulated in dauer larvae, after correction for mRNA load: genes encoding poly(A)-binding protein (PABP), heat-shock proteins hsp70 and hsp90, and three novel genes of uncertain function. The novel genes encode a partial homologue of human activating signal cointegrator 1 (ASC-1), a GTP-binding homologue of a ribosomal protein, and an SH3-domain protein. Transcript levels for all except hsp70 increased during aging in two C. elegans strains, whereas the three novel genes (and possibly PABP) were also induced to varying degrees by starvation of adults. All six genes are expressed at higher levels in young adults of long-lived daf mutant strains than in normal-longevity controls, suggesting that increased expression of these genes may play a protective function, thus favoring survival in diverse contexts.

[1]  D. Moore,et al.  Activating Signal Cointegrator 1, a Novel Transcription Coactivator of Nuclear Receptors, and Its Cytosolic Localization under Conditions of Serum Deprivation , 1999, Molecular and Cellular Biology.

[2]  C. K. Lee,et al.  Gene expression profile of aging and its retardation by caloric restriction. , 1999, Science.

[3]  G. Ruvkun,et al.  An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. , 1998, Genetics.

[4]  C. Kenyon,et al.  daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. , 1997, Science.

[5]  G. Ruvkun,et al.  The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans , 1997, Nature.

[6]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[7]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[8]  R. Goodman,et al.  The multifunctional role of the co-activator CBP in transcriptional regulation. , 1997, Recent progress in hormone research.

[9]  D. Livingston,et al.  The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Ruvkun,et al.  A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans , 1996, Nature.

[11]  B. Lakowski,et al.  Determination of Life-Span in Caenorhabditis elegans by Four Clock Genes , 1996, Science.

[12]  N. Shikama,et al.  Changes in the expression of genes involved in protein synthesis during Drosophila aging. , 1996, Gerontology.

[13]  B. O’Malley,et al.  Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor Superfamily , 1995, Science.

[14]  T. Johnson,et al.  Identification genes that are differentially expressed during aging in Caenorhabditis elegans. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[15]  D. Riddle,et al.  Genes that regulate both development and longevity in Caenorhabditis elegans. , 1995, Genetics.

[16]  B. Kennedy,et al.  Mutation in the silencing gene S/R4 can delay aging in S. cerevisiae , 1995, Cell.

[17]  N. Shikama,et al.  Protein synthesis elongation factor EF-1 alpha expression and longevity in Drosophila melanogaster. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  G. Ruvkun,et al.  daf-2, daf-16 and daf-23: genetically interacting genes controlling Dauer formation in Caenorhabditis elegans. , 1994, Genetics.

[19]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[20]  R. Weindruch,et al.  Caloric restriction, aging, and antioxidant enzymes. , 1993, Mutation research.

[21]  V. Cherkasova,et al.  Longevity-determining genes in Caenorhabditis elegans: chromosomal mapping of multiple noninteractive loci. , 1993, Genetics.

[22]  D. Riddle,et al.  The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development , 1993, Nature.

[23]  J. Thomas,et al.  Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. , 1993, Genetics.

[24]  E. Craig,et al.  Heat shock proteins: molecular chaperones of protein biogenesis , 1993, Microbiological reviews.

[25]  M. Matsuo,et al.  Oxygen-dependent perturbation of life span and aging rate in the nematode. , 1993, Journal of gerontology.

[26]  P Cicchetti,et al.  Identification of a ten-amino acid proline-rich SH3 binding site. , 1993, Science.

[27]  F. Hartl,et al.  Molecular chaperone functions of heat-shock proteins. , 1993, Annual review of biochemistry.

[28]  R. Moon,et al.  Purification and characterization of recombinant Xenopus poly(A)(+)-binding protein expressed in a baculovirus system. , 1992, The Biochemical journal.

[29]  A. Sachs,et al.  Translation initiation requires the PAB-dependent poly(A) ribonuclease in yeast , 1992, Cell.

[30]  M. Golomb,et al.  Gene expression in the Caenorhabditis elegans dauer larva: developmental regulation of Hsp90 and other genes. , 1992, Developmental biology.

[31]  M. Adams,et al.  Caenorhabditis elegans expressed sequence tags identify gene families and potential disease gene homologues , 1992, Nature Genetics.

[32]  N. Halloran,et al.  A survey of expressed genes in Caenorhabditis elegans , 1992, Nature Genetics.

[33]  J. Thomas,et al.  Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans. , 1992, Genetics.

[34]  P. Bazzicalupo,et al.  cut-1 a Caenorhabditis elegans gene coding for a dauer-specific noncollagenous component of the cuticle. , 1991, Developmental biology.

[35]  P. R. Sibbald,et al.  The P-loop--a common motif in ATP- and GTP-binding proteins. , 1990, Trends in biochemical sciences.

[36]  M J Schlesinger,et al.  Heat shock proteins. , 1990, The Journal of biological chemistry.

[37]  D. Riddle,et al.  daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase , 1990, Cell.

[38]  S. Kottaridis,et al.  Subtraction hybridization cDNA libraries from colon carcinoma and hepatic cancer. , 1990, Genetic analysis, techniques and applications.

[39]  A. Niedzwiecki,et al.  Changes in protein turnover after heat shock are related to accumulation of abnormal proteins in aging Drosophila melanogaster , 1990, Mechanisms of Ageing and Development.

[40]  V. Ambros,et al.  Heterochronic genes control the stage-specific initiation and expression of the dauer larva developmental program in Caenorhabditis elegans. , 1989, Genes & Development.

[41]  G. Dreyfuss,et al.  RNA-binding proteins as developmental regulators. , 1989, Genes & development.

[42]  P. Dennis,et al.  Characterization of the L11, L1, L10 and L12 equivalent ribosomal protein gene cluster of the halophilic archaebacterium Halobacterium cutirubrum. , 1989, The EMBO journal.

[43]  C. Fields,et al.  Sequence comparisons of developmentally regulated collagen genes of Caenorhabditis elegans. , 1989, Gene.

[44]  D. Riddle,et al.  Developmental regulation of energy metabolism in Caenorhabditis elegans. , 1989, Developmental biology.

[45]  H. Sive,et al.  A simple subtractive hybridization technique employing photoactivatable biotin and phenol extraction. , 1988, Nucleic acids research.

[46]  D. Riddle,et al.  Acidic intracellular pH shift during Caenorhabditis elegans larval development. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[47]  A. Coulson,et al.  Genome linking with yeast artificial chromosomes , 1988, Nature.

[48]  K. Bensch,et al.  Aging results in an unusual expression of Drosophila heat shock proteins. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[49]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[50]  C. Harley,et al.  Hybridization of oligo(dT) to RNA on nitrocellulose. , 1987, Gene analysis techniques.

[51]  S. Lindquist,et al.  An ancient developmental induction: heat-shock proteins induced in sporulation and oogenesis. , 1986, Science.

[52]  L. G. Davis,et al.  Formaldehyde Gel for Electrophoretic Separation of RNA and Northern Blot , 1986 .

[53]  L. G. Davis,et al.  Basic methods in molecular biology , 1986 .

[54]  Susan L. Kline,et al.  Arresting development arrests aging in the nematode Caenorhabditis elegans , 1984, Mechanisms of Ageing and Development.

[55]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[56]  D. Hanahan.  Studies on transformation of Escherichia coli with plasmids. , 1983, Journal of molecular biology.

[57]  G. Anderson.  Superoxide dismutase activity in dauerlarvae of Caenorhabditis elegans (Nematoda: Rhabditidae) , 1982 .

[58]  R. Hosono,et al.  Age-dependent changes in mobility and separation of the nematode Caenorhabditis elegans , 1980, Experimental Gerontology.

[59]  H. Horvitz,et al.  The nematode Caenorhabditis elegans. , 1980 .

[60]  Georg E. Schulz,et al.  Principles of Protein Structure , 1979 .

[61]  S. W. Emmons,et al.  Analysis of the constancy of DNA sequences during development and evolution of the nematode Caenorhabditis elegans. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[62]  D. H. Mitchell,et al.  Synchronous growth and aging of Caenorhabditis elegans in the presence of fluorodeoxyuridine. , 1979, Journal of gerontology.

[63]  M. Klass,et al.  Aging in the nematode Caenorhabditis elegans: Major biological and environmental factors influencing life span , 1977, Mechanisms of Ageing and Development.

[64]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[65]  M. Klass,et al.  Non-ageing developmental variant of Caenorhabditis elegans , 1976, Nature.

[66]  R. Cassada,et al.  The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. , 1975, Developmental biology.

[67]  S. Brenner.  The genetics of Caenorhabditis elegans. , 1974, Genetics.