1. MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans.
- Author
-
Riesen M, Feyst I, Rattanavirotkul N, Ezcurra M, Tullet JM, Papatheodorou I, Ziehm M, Au C, Gilliat AF, Hellberg J, Thornton JM, and Gems D
- Subjects
- Animals, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, DNA-Binding Proteins genetics, Female, Forkhead Transcription Factors, Genes, myc, Hyperplasia, Hypertrophy, Intestinal Mucosa metabolism, Oocytes growth & development, Uterine Neoplasms genetics, Aging metabolism, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins metabolism, DNA-Binding Proteins metabolism, Transcription Factors metabolism
- 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.
- Published
- 2014
- Full Text
- View/download PDF