TY - JOUR
T1 - Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress
AU - Salmon, Adam B.
AU - Murakami, Shin
AU - Bartke, Andrzej
AU - Kopchick, John
AU - Yasumura, Kyoko
AU - Miller, Richard A.
PY - 2005/7
Y1 - 2005/7
N2 - Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to the cytotoxic effects of H2O2, cadmium, UV light, paraquat, and heat. We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H 2O2, paraquat, and UV but not to cadmium. Resistance to UV light, cadmium, and H2O2 are similar in cells derived from 1-wk-old Snell dwarf or normal mice, and thus the resistance of cell lines derived from young adult donors reflects developmental processes, presumably hormone dependent, that take place in the first few months of life. The resistance of cells from Snell dwarf mice to these stresses does not reflect merely antioxidant defenses: dwarf-derived cells are also resistant to the DNA-alkylating agent methyl methanesulfonate. Furthermore, inhibitor studies show that fibroblast resistance to UV light is unaffected by the antioxidants ascorbic acid and N-acetyl-L-cysteine. These data suggest that postnatal exposure to altered levels of pituitary hormones leads to development of cellular resistance to oxidative and nonoxidative stressors, which are stable through many rounds of in vitro cell division and could contribute to the remarkable disease resistance of long-lived mutant mice.
AB - Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to the cytotoxic effects of H2O2, cadmium, UV light, paraquat, and heat. We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H 2O2, paraquat, and UV but not to cadmium. Resistance to UV light, cadmium, and H2O2 are similar in cells derived from 1-wk-old Snell dwarf or normal mice, and thus the resistance of cell lines derived from young adult donors reflects developmental processes, presumably hormone dependent, that take place in the first few months of life. The resistance of cells from Snell dwarf mice to these stresses does not reflect merely antioxidant defenses: dwarf-derived cells are also resistant to the DNA-alkylating agent methyl methanesulfonate. Furthermore, inhibitor studies show that fibroblast resistance to UV light is unaffected by the antioxidants ascorbic acid and N-acetyl-L-cysteine. These data suggest that postnatal exposure to altered levels of pituitary hormones leads to development of cellular resistance to oxidative and nonoxidative stressors, which are stable through many rounds of in vitro cell division and could contribute to the remarkable disease resistance of long-lived mutant mice.
KW - Aging
KW - Insulin-like growth factor I
KW - Life span
KW - Oxidation
KW - Snell dwarf
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U2 - 10.1152/ajpendo.00575.2004
DO - 10.1152/ajpendo.00575.2004
M3 - Article
C2 - 15701676
AN - SCOPUS:21044450084
SN - 0193-1849
VL - 289
SP - E23-E29
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 1 52-1
ER -