ArticleProceedings of the National Academy of Sciences of the United States of America2016
Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Capsaicin responses in Drosophila: Exploring the possibility of establishing a new Non-TRPV1 model.Biochemistry and biophysics reports · 2026Review
- Identification, expression profiling and potential functional roles of nuclear receptors in the social aphid Pseudoregma bambucicola.BMC genomics · 2025Article
- Nuclear genome assembly of Leucinodes orbonalis (Lepidoptera: Crambidae) collected from the Philippines.Journal of insect science (Online) · 2025Article
- Queen bee gut microbiota extends honeybee lifespan by inhibiting insulin signaling.Applied and environmental microbiology · 2024Article
- A detoxification pathway initiated by a nuclear receptor TcHR96h in Tetranychus cinnabarinus (Boisduval).PLoS genetics · 2023Article
- Article
- A General Signal Pathway to Regulate Multiple Detoxification Genes Drives the Evolution ofInternational journal of molecular sciences · 2022Article
- Chili-supplemented food decreases glutathione-Redox report : communications in free radical research · 2022Article
- Transient rapamycin treatment during developmental stage extends lifespan in Mus musculus and Drosophila melanogaster.EMBO reports · 2022Article
- Semelparous Death as one Element of Iteroparous Aging Gone Large.Frontiers in genetics · 2022Article
- Article
- Tissue-specific modulation of gene expression in response to lowered insulin signalling ineLife · 2021Article
- Short term transcriptional responses of P450s to phytochemicals in insects and mites.Current opinion in insect science · 2021Review
- TheeLife · 2020Article
- MAPK-directed activation of the whitefly transcription factorProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The neuronal receptor tyrosine kinase Alk is a target for longevity.Aging cell · 2020Article
- Molecular Characterization and Expression Profiling of Nuclear Receptor Gene Families in Oriental Fruit Fly,Insects · 2020Article
- Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production.Aging cell · 2020Article
- High-resolution QTL mapping in Tetranychus urticae reveals acaricide-specific responses and common target-site resistance after selection by different METI-I acaricides.Insect biochemistry and molecular biology · 2019Article
- The expression of Spodoptera exigua P450 and UGT genes: tissue specificity and response to insecticides.Insect science · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice.
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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.