Alterations in xenobiotic metabolism in the long‐lived Little mice

摘要: Our previous microarray expression analysis of the long-lived Little mice (Ghrhr(lit/lit)) showed a concerted up-regulation xenobiotic detoxification genes. Here, we show that this is associated with potent increase in resistance against adverse effects variety xenobiotics, including hepatotoxins acetaminophen and bromobenzene paralyzing agent zoxazolamine. The classic receptors Car (Constitutive Androstane Receptor) Pxr (Pregnane X are considered key regulators metabolism. Using double triple knockout/mutant mouse models found, however, not required for genes mice. results suggest instead bile acids primary acid receptor Fxr (farnesoid receptor) likely mediators Bile levels considerably elevated bile, serum, liver We found treatment wild-type animals cholic acid, one major mice, mimics large part observed Additionally, loss had effect on up-regulated A fraction these lost or decreased their high mutant Ghrhr. alterations metabolism constitute form increased stress may contribute to extended longevity