Greater resistance to inflammation at adulthood could contribute to extended life span of p66Shc-/- mice

Alessandra Berry, Daniela Carnevale, Marco Giorgio, Pier Giuseppe Pelicci, Edo Ronald de Kloet, Enrico Alleva, Luisa Minghetti, Francesca Cirulli

Research output: Contribution to journalArticlepeer-review

Abstract

Evidence is mounting that reactive oxygen species (ROS) produced because of stressful challenges could interfere with the proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in greater vulnerability to aging and neurodegeneration. Here we tested the hypothesis that p66Shc-/- mice, which have been described to have an extended life span and a high resistance to oxidative stress, might be less susceptible to the effects of inflammatory insults at adulthood. Although adrenocortical reactivity in response to bacterial endotoxin (lipopolysaccharide, LPS) did not differ as a function of the genotype, a hyperdrive of the HPA axis was revealed following treatment with a synthetic glucocorticoid agonist. When measuring changes in hippocampal oxidative status following LPS, only wild-type (WT) subjects showed increased levels of F2-isoprostanes, an index of lipid peroxidation and free radical formation. At the same time, the neurotrophin brain-derived neurotrophic factor was selectively increased in WT subjects, while levels of prostaglandin E2 were decreased in the mutants. Overall, the greater resilience to inflammation-induced changes in the p66Shc-/- mutants might underlie the better health status and the longevity characterizing these mice.

Original languageEnglish
Pages (from-to)343-350
Number of pages8
JournalExperimental Gerontology
Volume45
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Aging
  • Brain-derived neurotrophic factor (BDNF)
  • Hypothalamic-pituitary-adrenal (HPA) axis
  • Inflammation
  • Isoprostanes (15-F-IsoP)
  • Lipopolysaccharide (LPS)
  • Oxidative stress (OS)
  • Transgenic mice

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology

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