Stress resistance and aging: Influence of genes and nutrition

James M. Harper, Adam B. Salmon, Yayi Chang, Michael Bonkowski, Andrzej Bartke, Richard A. Miller

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf (d w / d w), Ames dwarf (df/df) and growth hormone receptor knockout (GHR-KO) mouse stocks are resistant, in vitro, to the cytotoxic effects of hydrogen peroxide, cadmium, ultraviolet light, paraquat, and heat. Here we show that, in contrast, fibroblasts from mice on low-calorie (CR) or low methionine (Meth-R) diets are not stress resistant in culture, despite the longevity induced by both dietary regimes. A second approach, involving induction of liver cell death in live animals using acetaminophen (APAP), documented hepatotoxin resistance in the CR and Meth-R mice, but d w / d w and GHR-KO mutant mice were not resistant to this agent, and were in fact more susceptible than littermate controls to the toxic effects of APAP. These data thus suggest that while resistance to stress is a common characteristic of experimental life span extension in mice, the cell types showing resistance may differ among the various models of delayed or decelerated aging.

Original languageEnglish (US)
Pages (from-to)687-694
Number of pages8
JournalMechanisms of Ageing and Development
Issue number8
StatePublished - Aug 2006
Externally publishedYes


  • Caloric restriction
  • Growth hormone receptor knockout
  • Methionine restriction
  • Snell dwarf
  • Stress resistance

ASJC Scopus subject areas

  • Aging
  • Developmental Biology


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