Maintenance of Proteostasis by P Body-Mediated Regulation of eIF4E Availability during Aging in Caenorhabditis elegans

Rieckher M, Markaki M, Princz A, Schumacher B, Tavernarakis N

Cell Rep 2018 Oct;25(1):199-211.e6

PMID: 30282029


Aging is accompanied by a pervasive collapse of proteostasis, while reducing general protein synthesis promotes longevity across taxa. Here, we show that the eIF4E isoform IFE-2 is increasingly sequestered in mRNA processing (P) bodies during aging and upon stress in Caenorhabditis elegans. Loss of the enhancer of mRNA decapping EDC-3 causes further entrapment of IFE-2 in P bodies and lowers protein synthesis rates in somatic tissues. Animals lacking EDC-3 are long lived and stress resistant, congruent with IFE-2-deficient mutants. Notably, neuron-specific expression of EDC-3 is sufficient to reverse lifespan extension, while sequestration of IFE-2 in neuronal P bodies counteracts age-related neuronal decline. The effects of mRNA decapping deficiency on stress resistance and longevity are orchestrated by a multimodal stress response involving the transcription factor SKN-1, which mediates lifespan extension upon reduced protein synthesis. Our findings elucidate a mechanism of proteostasis control during aging through P body-mediated regulation of protein synthesis in the soma.

  • Upcoming Events

    1. “Collagen secretion in Health and Disease”

      June 26 @ 5:15 pm - 6:15 pm
    2. Women in Science and Society lecture with Prof. Susan E Quaggin

      July 1 @ 12:30 pm - 7:00 pm
    3. 4th Connector Meeting

      September 6 @ 3:00 pm - 6:30 pm
    4. 5th Connector Meeting

      November 8 @ 3:00 pm - 6:00 pm
  • News

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.