Life-long vitamin C supplementation in combination with cold exposure does not affect oxidative damage or lifespan in mice, but decreases expression of antioxidant protection genes

Selman, Colin; McLaren, James; Meyer, Claus; Duncan, Jackie; Redman, Paula; Collins, Andrew; Duthie, Garry G.; Speakman, John R.

doi:10.1016/j.mad.2006.09.008

Cited by 78 publications

(74 citation statements)

References 49 publications

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“…From 12 weeks of age onward, and as previously described, 26 mice were maintained at 7 Ϯ 2°C within a controlled temperature room (Atlantic Cooling Services, Scassow, UK), with access to bedding material and water and ad libitum access to standard mouse diet (Rat and Mouse Maintenance (RMI), Special Diets Services, BP Nutrition, Witham, UK). Over a 4 week period of acclimation to 7 Ϯ 2°C, bedding material was gradually removed and then at 16 weeks of age the mice were randomly assigned to a control RM1 diet group (22 mg/kg ad libitum ␣-tocopherol) or a ␣-tocopherol supplemented group (RM1 ϩ 550 mg/kg of ␣-tocopherol) equivalent to 25 ϫ the control diet.…”

Section: Experimental Design and Mouse Husbandrymentioning

confidence: 99%

“…All individuals were monitored daily following the guidelines described previously, 26 with Kaplan-Meier survival curves constructed using birth (mice purchased at 8 weeks of age, see above) and known death dates of each individual. The oldest 10% survival was determined as the age of death of the oldest 10% of mice in each experimental cohort.…”

Section: Longevity Analysismentioning

confidence: 99%

“…17 Secondly, Vitamin E may scavenge ROS, and ROS may be important in the aging process, but this effect might be offset by a parallel compensating impacts on the endogenous antioxidant system, or indeed on any system involved in redox status or oxidative damage, similar to those reported following vitamin C supplementation. 25,26 Thirdly, because body mass and energy metabolism affect both free-radical production and life span, 7,27,28 if vitamin E supplementation influences one or both of these factors, this could offset any potential benefits. Finally, age of initiation of supplementation may be important.…”

Section: Introduction Imentioning

confidence: 99%

“…[29][30][31][32] Therefore, to examine whether lifelong ␣-tocopherol supplementation (initiated at 4 months of age) had a beneficial effect on oxidative stress and life span, we maintained C57BL/6 mice at 7 Ϯ 2°C over their lifetime to potentially increase metabolic rate, ROS production, and oxidative damage. We have previously hypothesized 26 that under conditions of cold exposure, we would be more likely to detect an effect of antioxidant supplementation on oxidative stress and life span if such an effect existed. We measured life span, energy balance (resting metabolic rate, daily energy expenditure by doubly-labeled water 33 ) hepatic lipid peroxidation (thiobarbituric acidreactive substances [TBAR]) using an HPLC method, 26,34 and lymphocyte and hepatocyte DNA oxidative damage (modified Comet assay) in male and female C57BL/6 mice maintained in the cold (7 Ϯ 2°C) with ad libitum access to either a control or an ␣-tocopherol (550 mg/kg) supplemented diet.…”

Section: Introduction Imentioning

confidence: 99%

“…We have previously hypothesized 26 that under conditions of cold exposure, we would be more likely to detect an effect of antioxidant supplementation on oxidative stress and life span if such an effect existed. We measured life span, energy balance (resting metabolic rate, daily energy expenditure by doubly-labeled water 33 ) hepatic lipid peroxidation (thiobarbituric acidreactive substances [TBAR]) using an HPLC method, 26,34 and lymphocyte and hepatocyte DNA oxidative damage (modified Comet assay) in male and female C57BL/6 mice maintained in the cold (7 Ϯ 2°C) with ad libitum access to either a control or an ␣-tocopherol (550 mg/kg) supplemented diet. In addition, Clontech cDNA-macroarrays were used to exam-ine hepatic gene expression changes with age and ␣-tocopherol supplementation in female mice.…”

Section: Introduction Imentioning

confidence: 99%

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Lifelongα-Tocopherol Supplementation Increases the Median Life Span of C57BL/6 Mice in the Cold but Has Only Minor Effects on Oxidative Damage

Selman

McLaren

Mayer

et al. 2008

Rejuvenation Research

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. (2008) Lifelongα-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage. Rejuvenation Research, 11 (1 ABSTRACTThe effects of dietary antioxidant supplementation on oxidative stress and life span are confused. We maintained C57BL/6 mice at 7 ؎ 2°C and supplemented their diet with ␣-tocopherol from 4 months of age. Supplementation significantly increased (p ‫؍‬ 0.042) median life span by 15% (785 days, n ‫؍‬ 44) relative to unsupplemented controls (682 days, n ‫؍‬ 43) and also increased maximum life span (oldest 10%, p ‫؍‬ 0.028). No sex or sex by treatment interaction effects were observed on life span, with treatment having no effect on resting or daily metabolic rate. Lymphocyte and hepatocyte oxidative DNA damage and hepatic lipid peroxidation were unaffected by supplementation, but hepatic oxidative DNA damage increased with age. Using a cDNA macroarray, genes associated with xenobiotic metabolism were significantly upregulated in the livers of female mice at 6 months of age (2 months supplementation). At 22 months of age (18 months supplementation) this response had largely abated, but various genes linked to the p21 signaling pathway were upregulated at this time. We suggest that ␣-tocopherol may initially be metabolized as a xenobiotic, potentially explaining why previous studies observe a life span extension generally when lifelong supplementation is initiated early in life. The absence of any significant effect on oxidative damage suggests that the life span extension observed was not mediated via any antioxidant properties of ␣-tocopherol. We propose that the life span extension observed following ␣-tocopherol supplementation may be mediated via upregulation of cytochrome p450 genes after 2 months of supplementation and/or upregulation of p21 signaling genes after 18 months of supplementation. However, these signaling pathways now require further investigation to establish their exact role in life span extension following ␣-tocopherol supplementation. 83

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Section: Experimental Design and Mouse Husbandrymentioning

confidence: 99%

Section: Longevity Analysismentioning

confidence: 99%