Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria

López-Torres, Mónica; Gredilla, Ricardo; Sanz, Alberto; Barja, Gustavo

doi:10.1016/s0891-5849(02)00773-6

Cited by 251 publications

(175 citation statements)

References 39 publications

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“…Such discrepancies were also found when CR was extended to 4-6 months 29,35 or 12-18 months. 26,28 In the present study, we found that isolated liver mitochondria from Lou/C rats, which display an inborn LCI, [1][2][3][7][8][9]14,15 produced more H 2 O 2 than Wistar rats fed ad libitum or even pair-fed. The enhanced H 2 O 2 generation displayed by Lou/C mitochondria takes place at many levels of the electron transport chain.…”

Section: Discussionmentioning

confidence: 52%

“…The ROS generation in liver is well documented, [25][26][27][28][29][30] and many cellular sources of ROS production have been identified, including plasma membrane NADPH oxidase and xanthine, peroxisomal and endoplasmic reticular oxidases. However, it is now generally accepted that mitochondrial electron transport chain represents the major source of ROS.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is now generally accepted that mitochondrial electron transport chain represents the major source of ROS. [25][26][27][28][29][30][31] While it was initially thought that complex III was the main or even the only site of ROS generation, 32 recent investigations unequivocally demonstrated that respiratorychain complex I is the major generator of free radicals in liver mitochondria. 16,31 One of the most important finding of our study is the demonstration that in the absence of any inhibitor, hepatic mitochondria energized with G/M/S generated H 2 O 2 to a significant extent (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…34 Higher liver mitochondrial H 2 O 2 production in Lou/C rats In a pioneer study, Gredilla et al 25 reported that short-term CR (6 week) reduced H 2 O 2 production by liver mitochondria, Low caloric intake and liver mitochondria G Lacraz et al this effect being confirmed with prolongation of CR up to 12 months. 28 Nevertheless, the widespread notion of a reduced rate of H 2 O 2 generation by liver mitochondria with CR was recently challenged by some authors. 26,29 Thus, a similar reduction in caloric intake (B40%) for 4-8 weeks was found either to decrease 25 or to enhance 29 mitochondrial H 2 O 2 production.…”

Section: Discussionmentioning

confidence: 99%

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Liver mitochondrial properties from the obesity-resistant Lou/C rat

et al. 2008

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Objective: The first objective was to evaluate the influence of caloric intake on liver mitochondrial properties. The second objective was aimed at determining the impact of increasing fat intake on these properties. Design: Lou/C rats, displaying an inborn low caloric intake and resistant to diet-induced obesity, were compared to Wistar rats fed either ad libitum or pair-fed. An additional group of Lou/C rats were allowed to increase their fat intake by adjusting their diet from a standard high carbohydrate low-fat diet to a high-fat carbohydrate-free diet. Measurements: Hydrogen peroxide (H 2 O 2 ) generation, oxygen consumption rate (J O2 ), membrane potential (DC), activity of respiratory chain complexes, cytochrome contents, oxidative phosphorylation efficiency (OPE) and uncoupling protein 2 (UCP2) expression were determined in liver mitochondria. Results: H 2 O 2 production was higher in Lou/C than Wistar rats with glutamate/malate and/or succinate, octanoyl-carnitine, as substrates. These mitochondrial features cannot be mimicked by pair-feeding Wistar rats and remained unaltered by increasing fat intake. Enhanced H 2 O 2 production by mitochondria from Lou/C rats is due to an increased reverse electron flow through the respiratory-chain complex I and a higher medium-chain acyl-CoA dehydrogenase activity. While J O 2 was similar over a large range of DC in both strains, Lou/C rats were able to sustain higher membrane potential and respiratory rate. In addition, mitochondria from Lou/C rats displayed a decrease in OPE that cannot be explained by increased expression of UCP2 but rather to a slip in proton pumping by cytochrome oxidase. Conclusions: Liver mitochondria from Lou/C rats display higher reactive oxygen species (ROS) generation but to deplete upstream electron-rich intermediates responsible for ROS generation, these animals increased intrinsic uncoupling of cytochrome oxidase. It is likely that liver mitochondrial properties allowed this strain of rat to display higher insulin sensitivity and resist diet-induced obesity.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Liver mitochondrial properties from the obesity-resistant Lou/C rat

et al. 2008

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“…Another possibility is measuring reactive oxygen species (ROS) that hosts use in an oxidative burst to kill micro- (Miller and Britigan 1997) and macro-parasites (Bender et al 2005). It is well known that CR decreases production of ROS during normal metabolism (Lopez-Torres et al 2002;Ward et al 2005); this is considered to be beneficial because CR animals incur less oxidative damage than AL animals (Merry 2002). However, if CR also decreases the ability to produce ROS needed to kill pathogens, CR could become a liability.…”

Section: Benefits Of Using Intact Pathogensmentioning

confidence: 99%

Calorie restriction and susceptibility to intact pathogens

Kristan

2008

AGE

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Long-term calorie restriction (CR) causes numerous physiological changes that ultimately increase mean and maximum lifespan of most species examined to date. One physiological change that occurs with CR is enhanced immune function, as tested using antigens and mitogens to stimulate an immune response. Fewer studies have used intact pathogen exposure to test whether the enhanced capacity of the immune response during CR actually decreases susceptibility of hosts to their pathogens. So far, studies using intact bacteria, virus, and helminth worm exposure indicate that, despite similar or enhanced immune system function, CR hosts are more susceptible to infection by intact pathogens than their fully fed counterparts. Long-term CR studies that examine susceptibility to a variety of parasite taxa will help determine if direct CR or CR mimetics will be beneficial to people living in pathogen-rich environments.

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Caloric Restriction and Oxidative Stress

Škrha

2011

Oxidative Stress in Vertebrates and Invertebrates

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Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria

Cited by 251 publications

References 39 publications

Liver mitochondrial properties from the obesity-resistant Lou/C rat

Liver mitochondrial properties from the obesity-resistant Lou/C rat

Calorie restriction and susceptibility to intact pathogens

Caloric Restriction and Oxidative Stress

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