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MDL‐1, a growth‐ and tumor‐suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

Riesen, Michèle, Feyst, Inna, Rattanavirotkul, Nattaphong, Ezcurra, Marina, Tullet, Jennifer M.A., Papatheodorou, Irene, Ziehm, Matthias, Au, Catherine, Gilliat, Ann F., Hellberg, Josephine, and others. (2014) MDL‐1, a growth‐ and tumor‐suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans. Aging, 6 (2). pp. 98-117. ISSN 1945-4589. (doi:10.18632/aging.100638) (KAR id:91120)

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https://doi.org/10.18632/aging.100638

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.

Item Type: Article
DOI/Identification number: 10.18632/aging.100638
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Marina Ezcurra
Date Deposited: 27 Oct 2021 16:04 UTC
Last Modified: 28 Oct 2021 15:03 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/91120 (The current URI for this page, for reference purposes)
Ezcurra, Marina: https://orcid.org/0000-0003-2739-6984
Tullet, Jennifer M.A.: https://orcid.org/0000-0002-2037-526X
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