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. 2006 Aug;127(8):687-94.
doi: 10.1016/j.mad.2006.04.002. Epub 2006 May 19.

Stress resistance and aging: influence of genes and nutrition

James M Harper  1 , Adam B Salmon, Yayi Chang, Michael Bonkowski, Andrzej Bartke, Richard A Miller
Affiliations

Stress resistance and aging: influence of genes and nutrition

James M Harper et al. Mech Ageing Dev. 2006 Aug.

Abstract

Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf (dw/dw), 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 dw/dw 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.

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Figures

Fig. 1
Fig. 1
Mean (±S.E.) LD50 for ultraviolet radiation, hydrogen peroxide, and cadmium in fibroblast cell lines derived from: young (top panels) and old (middle panels) calorie restricted (CR) CB6F1 females, as well as young (bottom panels) methionine-restricted (Meth-R) CB6F1 females. There are no significant differences relative to the controls (AL-C, Meth-C) by t-test (p > 0.08 for all). N = 6–9 mice per group.
Fig. 2
Fig. 2
Serum alanine aminotransferase (ALT; left) and lactate dehydrogenase (LDH; right) activity in response to a single acetaminophen (APAP challenge) in AL-C vs. CR female CB6F1 mice (top panels), female Snell dwarf (dw/dw) vs. normal littermate control mice (dw/+; middle panels), and male GHR-KO vs. wild-type control mice (WT; bottom panels). Each point represents the mean (±S.E.) for each group at each of the indicated times. *Indicates a significant difference at p < 0.05 vs. the respective control group. †Indicates all individuals died as a result of APAP toxicity. N = 8 per group for AL-C and CR mice, three per group for dw/dw and dw/+ mice, and eight per group for GHR-KO and WT mice. Note that N = 7 at the 48 h time point for GHR-KO mice due to APAP-induced mortality. See text for details.
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References

    1. Ahluwalia A, Clodfelter KH, Waxman DJ. Sexual dimorphism of rat liver gene expression: regulatory role of growth hormone revealed by deoxyribonucleic acid microarray analysis. Mol. Endocrinol. 2004;18:747–760. - PubMed
    1. Aidoo A, Desai VG, Lyn-Cook LE, Chen JJ, Feuers RJ, Casciano DA. Attenuation of bleomycin-induced Hprt mutant frequency in female and male rats by calorie restriction. Mutation Res. 1999;430:155–163. - PubMed
    1. Apte UM, Limaye PB, Desaiah D, Bucci TJ, Warbritton A, Mehendale HM. Mechanisms of increased liver tissue repair and survival in diet-restricted rats treated with equitoxic doses of thioacetamide. Toxicol. Sci. 2003;72:272–282. - PubMed
    1. Arking R. Gene expression and regulation in the extended longevity phenotypes of Drosophila. Ann. N.Y. Acad. Sci. 2001;928:157–167. - PubMed
    1. Bartke A, Brown-Borg H. Life extension in the dwarf mouse. Curr. Top. Dev. Biol. 2004;63:189–225. - PubMed

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