The adaptor protein 14-3-3zeta modulates intestinal immunity and aging in Drosophila.

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      14-3-3 Proteins*/genetics ; 14-3-3 Proteins*/metabolism ; Aging*/genetics ; Drosophila melanogaster*/growth & development ; Drosophila melanogaster*/immunology ; Drosophila Proteins*/genetics ; Drosophila Proteins*/metabolism ; Intestines*/immunology; Animals ; Longevity ; Signal Transduction
    • Abstract:
      The proteins that coordinate the complex transcriptional networks of aging have not been completely documented. Protein 14-3-3zeta is an adaptor protein that coordinates signaling and transcription factor networks, but its function in aging is not fully understood. Here, we showed that the protein expression of 14-3-3zeta gradually increased during aging. High levels of 14-3-3zeta led to shortened lifespan and imbalance of intestinal immune homeostasis in Drosophila, but the decrease in 14-3-3zeta protein levels by RNAi was able to significantly promote the longevity and intestinal immune homeostasis of fruit flies. Importantly, we demonstrate that adult-onset administration of TIC10, a compound that reduces the aging-related AKT and extracellular signal-regulated kinase (ERK) signaling pathways, rescues the shortened lifespan of 14-3-3zeta-overexpressing flies. This finding suggests that 14-3-3zeta plays a critical role in regulating the aging process. Our study elucidates the role of 14-3-3zeta in natural aging and provides the rationale for subsequent 14-3-3zeta-based antiaging research.
      Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
      (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: 14-3-3zeta; Drosophila; aging; intestinal immunity; lifespan
    • Accession Number:
      0 (14-3-3 Proteins)
      0 (Drosophila Proteins)
    • Publication Date:
      Date Created: 20231102 Date Completed: 20240129 Latest Revision: 20240129
    • Publication Date:
      20240129
    • Accession Number:
      PMC10724694
    • Accession Number:
      10.1016/j.jbc.2023.105414
    • Accession Number:
      37918806