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CALORIE RESTRICTION REDUCES SUPEROXIDE PRODUCTION OF AGING MOUSE HYPOTHALAMUS
Author(s) -
Marbauch Christine S.,
Warman David B.,
Horwitz Barbara A.,
McDonald Roger B.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a815
Subject(s) - superoxide , calorie restriction , reactive oxygen species , endocrinology , medicine , chemistry , transgene , oxidative stress , genetically modified mouse , biology , biochemistry , gene , enzyme
Previous investigations suggested that calorie restriction in mice significantly reduces reactive oxygen species (ROS), decreasing oxidative damage and extending lifespan. Calorie‐restricted mice also increase expression of mitochondrial uncoupling proteins (UCPs), which have been suggested to reduce ROS generation. Thus, we hypothesized that the age‐related increase in ROS would be attenuated in transgenic mice that overexpress UCP2 (TG‐UCP2). To test this, we measured superoxide production in hypothalami from 8‐, 19‐ and 26‐month old female mice in the following ad libitum fed groups: TG‐UCP2 mice, UCP2 knockout mice, and C57BL/6 wild type (WT) mice. Measurements were also made in hypothalami from C57BL/6 mice calorie‐restricted to 70% of WT animals. Superoxide production in the fixed hypothalami was determined by measuring oxidation of fluorescent‐labeled dihydroethidium to ethidium. We found a significant age‐related increase in superoxide between 8 and 19 month WT mice without further increases at 26 months. Calorie restriction significantly reduced superoxide concentration compared to all other groups; and preliminary data suggest that increased UCP2 expression may contribute to this attenuation. (NIH grant AG19984; Genentech Support for Undergraduate Research)