論文 - 詳細
| RRC ID | 59383 |
|---|---|
| 著者 | Minniti AN, Arriagada H, Zúñiga S, Bravo-Zehnder M, Alfaro IE, Aldunate R. |
| タイトル | Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis. |
| ジャーナル | Aging Cell |
| Abstract |
The insulin-IGF-1/DAF-2 pathway has a central role in the determination of aging and longevity in Caenorhabditis elegans and other organisms. In this paper, we measured neuronal insulin secretion (using INS-22::Venus) during C. elegans lifespan and monitored how this secretion is modified by redox homeostasis. We showed that INS-22::Venus secretion fluctuates during the organism lifetime reaching maximum levels in the active reproductive stage. We also demonstrate that long-lived daf-2 insulin receptor mutants show remarkable low levels of INS-22::Venus secretion. In contrast, we found that short-lived mutant worms that lack the oxidation repair enzyme MSRA-1 show increased levels of INS-22::Venus secretion, specifically during the reproductive stage. MSRA-1 is a target of the insulin-IGF-1/DAF-2 pathway, and the expression of this antioxidant enzyme exclusively in the nervous system rescues the mutant insulin release phenotype and longevity. The msra-1 mutant phenotype can also be reverted by antioxidant treatment during the active reproductive stage. We showed for the first time that there is a pattern of neuronal insulin release with a noticeable increment during the peak of reproduction. Our results suggest that redox homeostasis can modulate longevity through the regulation of insulin secretion, and that the insulin-IGF-1/DAF-2 pathway could be regulated, at least in part, by a feedback loop. These findings highlight the importance of timing for therapeutic interventions aimed at improving health span. |
| 巻・号 | 18(1) |
| ページ | e12855 |
| 公開日 | 2019-2-1 |
| DOI | 10.1111/acel.12855 |
| PMID | 30456853 |
| PMC | PMC6351846 |
| MeSH | Acetylcysteine / pharmacology Aging / drug effects Aging / physiology* Animals Antioxidants / pharmacology Caenorhabditis elegans / drug effects Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Down-Regulation / drug effects Homeostasis* / drug effects Insulin / metabolism* Longevity / drug effects Models, Biological Motor Activity / drug effects Mutation / genetics Neurons / drug effects Neurons / metabolism* Oxidation-Reduction Reproduction / drug effects Signal Transduction / drug effects Time Factors |
| IF | 7.346 |
| 引用数 | 1 |
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オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1421 |