RRC ID 59383
Author Minniti AN, Arriagada H, Zúñiga S, Bravo-Zehnder M, Alfaro IE, Aldunate R.
Title Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis.
Journal 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.
Volume 18(1)
Pages e12855
Published 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
Times Cited 1
C.elegans tm1421