title: MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans.
abstract: In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality.
authors: Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors: Michèle
authors: M
authors: Riesen
authors: Inna
authors: I
authors: Feyst
authors: Nattaphong
authors: N
authors: Rattanavirotkul
authors: Marina
authors: M
authors: Ezcurra
authors: Jennifer M A
authors: JM
authors: Tullet
authors: Irene
authors: I
authors: Papatheodorou
authors: Matthias
authors: M
authors: Ziehm
authors: Catherine
authors: C
authors: Au
authors: Ann F
authors: AF
authors: Gilliat
authors: Josephine
authors: J
authors: Hellberg
authors: Janet M
authors: JM
authors: Thornton
authors: David
authors: D
authors: Gems
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors; D016259:Genes, myc; D006965:Hyperplasia; D006984:Hypertrophy; D007413:Intestinal Mucosa / Q000378:metabolism; D009865:Oocytes / Q000254:growth & development; D014157:Transcription Factors / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C115091:mdl-1 protein, C elegans