ArticleAging cell2007
Alterations in xenobiotic metabolism in the long-lived Little mice.
Article in Aging cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms.PLoS genetics · 2011Pooled it
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- Metabolomic signatures of extreme old age: findings from the New England Centenarian Study.GeroScience · 2026Article
- METABOLOMIC SIGNATURES OF EXTREME OLD AGE: FINDINGS FROM THE NEW ENGLAND CENTENARIAN STUDY.bioRxiv : the preprint server for biology · 2025Article
- Targeting farnesoid X receptor as aging intervention therapy.Acta pharmaceutica Sinica. B · 2025Article
- Aging-associated atrial fibrillation: A comprehensive review focusing on the potential mechanisms.Aging cell · 2024Review
- Increased intestinal bile acid absorption contributes to age-related cognitive impairment.Cell reports. Medicine · 2024Article
- Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions.Nature communications · 2023Article
- Semelparous Death as one Element of Iteroparous Aging Gone Large.Frontiers in genetics · 2022Article
- Host and microbiota metabolic signals in aging and longevity.Nature chemical biology · 2021Review
- Lipid metabolism and lipid signals in aging and longevity.Developmental cell · 2021Review
- Energy Metabolism and Aging.The world journal of men's health · 2021Review
- Article
- Mouse models of growth hormone deficiency.Reviews in endocrine & metabolic disorders · 2021Review
- The road ahead for health and lifespan interventions.Ageing research reviews · 2020Review
- KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants.Nature communications · 2019Article
- Inter-Individual Variability in Xenobiotic-Metabolizing Enzymes: Implications for Human Aging and Longevity.Genes · 2019Article
- Analysis of the coding sequences of clownfish reveals molecular convergence in the evolution of lifespan.BMC evolutionary biology · 2019Article
- Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism.Cell reports · 2018Article
- Sex-Specific Gene Expression and Life Span Regulation.Trends in endocrinology and metabolism: TEM · 2017Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Our previous microarray expression analysis of the long-lived Little mice (Ghrhr(lit/lit)) showed a concerted up-regulation of xenobiotic detoxification genes. Here, we show that this up-regulation is associated with a potent increase in resistance against the adverse effects of a variety of xenobiotics, including the hepatotoxins acetaminophen and bromobenzene and the paralyzing agent zoxazolamine. The classic xenobiotic receptors Car (Constitutive Androstane Receptor) and Pxr (Pregnane X Receptor) are considered key regulators of xenobiotic metabolism. Using double and triple knockout/mutant mouse models we found, however, that Car and Pxr are not required for the up-regulation of xenobiotic genes in Little mice. Our results suggest instead that bile acids and the primary bile acid receptor Fxr (farnesoid X receptor) are likely mediators of the up-regulation of xenobiotic detoxification genes in Little mice. Bile acid levels are considerably elevated in the bile, serum, and liver of Little mice. We found that treatment of wild-type animals with cholic acid, one of the major bile acids elevated in Little mice, mimics in large part the up-regulation of xenobiotic detoxification genes observed in Little mice. Additionally, the loss of Fxr had a major effect on the expression of the xenobiotic detoxification genes up-regulated in Little mice. A large fraction of these genes lost or decreased their high expression levels in double mutant mice for Fxr and Ghrhr. The alterations in xenobiotic metabolism in Little mice constitute a form of increased stress resistance and may contribute to the extended longevity of these 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.