RRC ID 46174
Author Riesen M, Feyst I, Rattanavirotkul N, Ezcurra M, Tullet JM, Papatheodorou I, Ziehm M, Au C, Gilliat AF, Hellberg J, Thornton JM, Gems D.
Title MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans.
Journal Aging (Albany NY)
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.
Volume 6(2)
Pages 98-117
Published 2014-2
DOI 10.18632/aging.100638
PII 100638
PMID 24531613
PMC PMC3969279
MeSH Aging / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Female Forkhead Transcription Factors Genes, myc Hyperplasia Hypertrophy Intestinal Mucosa / metabolism Oocytes / growth & development Transcription Factors / metabolism* Uterine Neoplasms / genetics
IF 5.515
Times Cited 11
WOS Category CELL BIOLOGY
Resource
C.elegans tm311