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Neuronal MML-1/MXL-2 regulates systemic aging via glutamate transporter and cell nonautonomous autophagic and peroxidase activity.
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- Author(s): Shioda T;Shioda T; Takahashi I; Takahashi I; Ikenaka K; Ikenaka K; Fujita N; Fujita N; Fujita N; Kanki T; Kanki T; Oka T; Oka T; Mochizuki H; Mochizuki H; Antebi A; Antebi A; Antebi A; Yoshimori T; Yoshimori T; Yoshimori T; Yoshimori T; Nakamura S; Nakamura S; Nakamura S; Nakamura S
- Source:
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2023 Sep 26; Vol. 120 (39), pp. e2221553120. Date of Electronic Publication: 2023 Sep 18.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
- Publication Information: Original Publication: Washington, DC : National Academy of Sciences
- Subject Terms:
- Abstract: Accumulating evidence has demonstrated the presence of intertissue-communication regulating systemic aging, but the underlying molecular network has not been fully explored. We and others previously showed that two basic helix-loop-helix transcription factors, MML-1 and HLH-30, are required for lifespan extension in several longevity paradigms, including germlineless Caenorhabditis elegans . However, it is unknown what tissues these factors target to promote longevity. Here, using tissue-specific knockdown experiments, we found that MML-1 and its heterodimer partners MXL-2 and HLH-30 act primarily in neurons to extend longevity in germlineless animals. Interestingly, however, the downstream cascades of MML-1 in neurons were distinct from those of HLH-30. Neuronal RNA interference (RNAi)-based transcriptome analysis revealed that the glutamate transporter GLT-5 is a downstream target of MML-1 but not HLH-30. Furthermore, the MML-1-GTL-5 axis in neurons is critical to prevent an age-dependent collapse of proteostasis and increased oxidative stress through autophagy and peroxidase MLT-7, respectively, in long-lived animals. Collectively, our study revealed that systemic aging is regulated by a molecular network involving neuronal MML-1 function in both neural and peripheral tissues.
- Comments: Erratum in: Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2318184120. (PMID: 37967225)
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- Accession Number: 0 (Amino Acid Transport System X-AG)
EC 1.11.1.- (Peroxidases)
0 (MML-1 protein, C elegans)
0 (MXL-2 protein, C elegans)
0 (Caenorhabditis elegans Proteins) - Publication Date: Date Created: 20230918 Date Completed: 20230928 Latest Revision: 20240319
- Publication Date: 20240319
- Accession Number: PMC10523562
- Accession Number: 10.1073/pnas.2221553120
- Accession Number: 37722055
- Source:
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