Research Paper Volume 6, Issue 2 pp 98—117
MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans
- 1 Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom
- 2 European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
Received: December 22, 2013 Accepted: February 14, 2014 Published: February 16, 2014https://doi.org/10.18632/aging.100638
How to Cite
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.