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ToolsSultanova, Zahida, Shen, Aykut, Hencel, Katarzyna, Carlsson, Hanne, Crighton, Zoe, Clifton, Daniel, Akay, Alper and Maklakov, Alexei A. (2025) Optimising age-specific insulin signalling to slow down reproductive ageing increases fitness in different nutritional environments. Aging Cell. ISSN 1474-9718
Full text not available from this repository. (Request a copy)Abstract
The developmental theory of ageing proposes that age-specific decline in the force of natural selection results in suboptimal levels of gene expression in adulthood, leading to functional senescence. This theory explicitly predicts that optimising gene expression in adulthood can ameliorate functional senescence and improve fitness. Reduced insulin/IGF-1 signalling (rIIS) extends the reproductive lifespan of Caenorhabditis elegans at the cost of reduced reproduction. Here, we show that adulthood-only rIIS improves late-life reproduction without any detrimental effects on other life-history traits in both benign and stressful conditions. Remarkably, we show that rIIS additively extends late-life reproduction and lifespan when animals are exposed to a fluctuating food environment—intermittent fasting (IF)—resulting in reduced food intake in early adulthood. Full factorial genome-wide RNA-Seq across the life course demonstrated that IF and rIIS modulate the age-specific expression of pro-longevity genes. IF, rIIS and combined IF + rIIS treatment downregulated genes involved in biosynthesis in early life and differentially regulated immunity genes in later life. Importantly, combined IF + rIIS treatment uniquely regulated a large cluster of genes in mid-life that are associated with immune response. These results suggest that optimising gene expression in adulthood can decelerate reproductive ageing and increase fitness.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: Z.S. was supported by Leverhulme Trust Early Career Fellowship (ECF-2022-214). A.A.M. was supported by ERC Consolidator Grant (GermlineAgeingSoma 724909) and NERC NE/W001020/1. A.A. and K.H. were supported by a UKRI Future Leaders Fellowship awarded to A.A. (grant number MR/S033769/1). A.S. was supported by the UKRI Biotechnology and Biological Sciences Research Council Norwich Research Park Biosciences Doctoral Training Partnership (grant number BB/T008717/1). |
| Uncontrolled Keywords: | ageing,developmental theory of ageing,life-history evolution,trade-offs,ageing,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1302 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Organisms and the Environment Faculty of Science > Research Centres > Centre for Ecology, Evolution and Conservation |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 27 Feb 2025 11:30 |
| Last Modified: | 07 Mar 2025 01:11 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98615 |
| DOI: | 10.1111/acel.14481 |
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