ArticleGenetics2021
Aging modulated by the Drosophila insulin receptor through distinct structure-defined mechanisms.
Article in Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Mutation in IR or IGF1R produces features of long-lived mice while maintaining metabolic health.JCI insight · 2025Article
- Structure and activation of the Drosophila insulin receptor by three Drosophila insulin-like peptides.Nature communications · 2025Article
- An insulin-sensitive Drosophila insulin-like receptor mutant remodels methionine metabolism to extend lifespan.PLoS genetics · 2025Article
- Gut-to-brain regulation ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gut-to-brain regulation ofbioRxiv : the preprint server for biology · 2024Article
- Biochemical characterization of the Drosophila insulin receptor kinase and longevity-associated mutants.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.Nature communications · 2023Article
- Article
- Randomization, design and analysis for interdependency in aging research: no person or mouse is an island.Nature aging · 2022Article
- Review
- Endocrine Regulation of Lifespan in Insect Diapause.Frontiers in physiology · 2022Review
- Anabolic Function Downstream of TOR Controls Trade-offs Between Longevity and Reproduction at the Level of Specific TissuesFrontiers in aging · 2021Article
- Review
- Aging Regulated Through a Stability Model of Insulin/Insulin Growth Factor Receptor Function.Frontiers in endocrinology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations of the Drosophila melanogaster insulin/IGF signaling system slow aging, while also affecting growth and reproduction. To understand this pleiotropy, we produced an allelic series of single codon substitutions in the Drosophila insulin receptor, InR. We generated InR substitutions using homologous recombination and related each to emerging models of receptor tyrosine kinase structure and function. Three mutations when combined as trans-heterozygotes extended lifespan while retarding growth and fecundity. These genotypes reduced insulin-stimulated Akt phosphorylation, suggesting they impede kinase catalytic domain function. Among these genotypes, longevity was negatively correlated with egg production, consistent with life-history trade-off theory. In contrast, one mutation (InR353) was located in the kinase insert domain, a poorly characterized element found in all receptor tyrosine kinases. Remarkably, wild-type heterozygotes with InR353 robustly extended lifespan without affecting growth or reproduction and retained capacity to fully phosphorylate Akt. The Drosophila insulin receptor kinase insert domain contains a previously unrecognized SH2 binding motif. We propose the kinase insert domain interacts with SH2-associated adapter proteins to affect aging through mechanisms that retain insulin sensitivity and are independent of reproduction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.