Live Fast, Die Old: Lowering Insulin Signalling During Development Can Speed Growth, Increase Reproduction and Lifespan, but Impair Environmental Sensing and Harm Offspring in Caenorhabditis elegans.
- 1School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK.
- 2Institute of Cell Biology, University of Bern, Bern, Switzerland.
Abstract
Genetic trade-offs can constrain life-history evolution resulting in the evolution of ageing. Reduced insulin/insulin-like signalling (rIIS) improves somatic maintenance and dramatically increases lifespan in Caenorhabditis elegans, but the effects on fitness are unclear. Here we used a novel experimental approach to show that, contrary to the prevailing paradigm, rIIS via daf-2 RNAi during development can improve development, reproduction, survival, individual fitness, and population growth rate in the laboratory and semi-natural conditions. However, developmental rIIS extends lifespan and improves fitness only in some temperatures, which explains why our results differ from previous findings. Furthermore, while developmental rIIS can improve a suite of life-history traits in parents, it slows down offspring development. Finally, because rIIS interferes with environmental sensing and compromises adaptive developmental plasticity in response to stress, a central part of C. elegans life history in nature, the ability to sense the environment correctly during development comes at the cost of accelerated senescence. These results suggest the complexity of gene-by-environment interactions during development imposes constraints on molecular signalling networks leading to genetic trade-offs across the life course that natural selection in late-life is unable to resolve. However, these constraints can be resolved by artificially fine-tuning gene expression at different ages.
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BibTeX
@article{irish2026live,
title = {{Live Fast, Die Old: Lowering Insulin Signalling During Development Can Speed Growth, Increase Reproduction and Lifespan, but Impair Environmental Sensing and Harm Offspring in Caenorhabditis elegans.}},
author = {Sara D Irish and Annabel Kimberley and Peter Lenart and Hanne Carlsson and Anna Braybrooke and Benjamin Towbin and Simone Immler and Alexei A Maklakov},
journal = {Aging cell},
year = {2026},
month = oct,
doi = {10.1111/acel.70783},
url = {https://europepmc.org/article/MED/42919816},
note = {CC BY},
}
RIS
TY - JOUR
TI - Live Fast, Die Old: Lowering Insulin Signalling During Development Can Speed Growth, Increase Reproduction and Lifespan, but Impair Environmental Sensing and Harm Offspring in Caenorhabditis elegans.
AU - Sara D Irish
AU - Annabel Kimberley
AU - Peter Lenart
AU - Hanne Carlsson
AU - Anna Braybrooke
AU - Benjamin Towbin
AU - Simone Immler
AU - Alexei A Maklakov
PY - 2026
DA - 2026/10/30
JO - Aging cell
DO - 10.1111/acel.70783
UR - https://europepmc.org/article/MED/42919816
AB - Genetic trade-offs can constrain life-history evolution resulting in the evolution of ageing. Reduced insulin/insulin-like signalling (rIIS) improves somatic maintenance and dramatically increases lifespan in Caenorhabditis elegans, but the effects on fitness are unclear. Here we used a novel experimental approach to show that, contrary to the prevailing paradigm, rIIS via daf-2 RNAi during development can improve development, reproduction, survival, individual fitness, and population growth rate in the laboratory and semi-natural conditions. However, developmental rIIS extends lifespan and improves fitness only in some temperatures, which explains why our results differ from previous findings. Furthermore, while developmental rIIS can improve a suite of life-history traits in parents, it slows down offspring development. Finally, because rIIS interferes with environmental sensing and compromises adaptive developmental plasticity in response to stress, a central part of C. elegans life history in nature, the ability to sense the environment correctly during development comes at the cost of accelerated senescence. These results suggest the complexity of gene-by-environment interactions during development imposes constraints on molecular signalling networks leading to genetic trade-offs across the life course that natural selection in late-life is unable to resolve. However, these constraints can be resolved by artificially fine-tuning gene expression at different ages.
SN - 1474-9718
SN - 1474-9726
ER -