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ToolsDuxbury, Elizabeth M. L., Carlsson, Hanne, Kimberley, Annabel, Ridge, Yvonne, Johnson, Katie and Maklakov, Alexei A. (2024) Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans. GeroScience, 46 (6). 5767–5780. ISSN 2509-2715
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Abstract
Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This study was funded by a European Research Council Consolidator Grant (GermlineAgeingSoma/724909) to AAM. |
| Uncontrolled Keywords: | anti-viral immunity,healthy aging,insulin signalling,orsay rna virus,rate-of-senescence,ageing,veterinary (miscalleneous),complementary and alternative medicine,geriatrics and gerontology,cardiology and cardiovascular medicine ,/dk/atira/pure/subjectarea/asjc/1300/1302 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Science Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Centres > Centre for Ecology, Evolution and Conservation Faculty of Science > Research Groups > Organisms and the Environment |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 24 Oct 2024 16:30 |
| Last Modified: | 06 Feb 2025 12:23 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97189 |
| DOI: | 10.1007/s11357-024-01147-7 |
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