Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis
| Autor: | Alicia N. Minniti, Hector Arriagada, Rebeca Aldunate, Soledad Zúñiga, Iván E. Alfaro, Marcela Bravo-Zehnder |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aging Time Factors media_common.quotation_subject medicine.medical_treatment Mutant Longevity Down-Regulation Motor Activity Models Biological Antioxidants 03 medical and health sciences 0302 clinical medicine medicine Animals Homeostasis Insulin Secretion Caenorhabditis elegans Caenorhabditis elegans Proteins media_common chemistry.chemical_classification Neurons Original Paper redox homeostasis biology Reproduction Cell Biology biology.organism_classification neuronal insulin Phenotype Original Papers Cell biology Acetylcysteine Insulin receptor 030104 developmental biology Enzyme chemistry Mutation biology.protein Oxidation-Reduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9726 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text